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    18 December 2020, Volume 24 Issue 35 Previous Issue    Next Issue
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    Treatment of knee osteoarthritis by tonifying kidney and spleen and activating blood circulation herbs via chondrocyte IL-1beta/ERR-alpha/SOX9/Col2alpha1 signaling pathway in a rat model
    Huo Shaochuan, Wang Haibin, Tang Hongyu, Wang Yueqi, Chen Qunqun, Feng Ziyu, Li Yikai
    2020, 24 (35):  5577-5581.  doi: 10.3969/j.issn.2095-4344.2881
    Abstract ( 352 )   PDF (518KB) ( 132 )   Save

    BACKGROUND: Knee osteoarthritis is the most common degenerative joint disease with high morbidity and disability, which severely threatens the life quality of patients. Chinese herbs that invigorate the kidney and spleen and activate blood circulation can improve the clinical symptoms of knee osteoarthritis, but its specific mechanism is still unclear.

    OBJECTIVE: To study the mechanism of invigorating kidney, invigorating spleen and activating blood circulation herbs regulating the IL-1β/ERRα/SOX9/Col2α1 signaling pathway in the treatment of knee osteoarthritis in ovariectomized rats.

    METHODS: Six-month-old female Sprague-Dawley rats were randomly divided into blank control group, model group, experimental group and positive control group. The ovariectomy and excision of the cruciate ligament and medial meniscus were performed in the latter three groups to make the rat models of knee osteoarthritis. Two weeks after operation, the rats were treated with invigorating kidney, invigorating spleen and activating blood circulation herbs, celecoxib capsules, or normal saline. Serum samples and knee cartilage tissues were collected after 6 weeks of continuous gastric administration. Serum estradiol content was detected by ELISA. Expression of IL-1β/ERRα/SOX9/Col2α1 signaling pathway in articular cartilage tissues was detected by fluorescence quantitative PCR and western blot.

    RESULTS AND CONCLUSION: Compared with the blank control group, the expression of IL-1β in the model group increased significantly, while the expression of estradiol, ERRα, SOX9 and Col2α1 decreased significantly (P < 0.05). Compared with the model group, the expression of IL-1β in the experimental group decreased significantly, while the expression of estradiol, ERRα, SOX9 and Col2α1 increased significantly (P < 0.05). Compared with the positive control group, the expression of IL-1β, ERRα, and Col2α1 in the experimental group was significantly increased, while the expression of SOX9 decreased significantly (P < 0.05). These results indicate that the IL-1β/ERRα/SOX9/Col2α1 signaling pathway is involved in knee osteoarthritis-induced cartilage lesion, and Chinese herbs for invigorating kidney and spleen and activating blood circulation play a therapeutic role through this mechanism.

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    Changes of bone metabolism after different intensity endurance exercises in growing rats
    Chen Zegang, Ding Haili, Li Long, Wang Chun
    2020, 24 (35):  5582-5588.  doi: 10.3969/j.issn.2095-4344.2918
    Abstract ( 315 )   PDF (554KB) ( 65 )   Save

    BACKGROUND: With the development of society and the improvement of people's living standards, the health of adolescents who are being in a period of sensitive growth and development has attracted increasing attention. Exercise can improve bone metabolism, but less is reported on the effect of endurance exercise on bone metabolism in growing rats.            

    OBJECTIVE: To investigate the effect of different intensity endurance exercises on bone metabolism in growing rats.

    METHODS: The experimental protocol was approved by the Animal Ethics Committee of the School of Sport and Health of Chengdu Sport University. After 1 week of adaptive training, 40 rats were randomly divided into three groups: quiet control group, low intensity endurance group, middle intensity endurance group and high intensity endurance group. The rats in the quiet control group were fed regularly without training intervention. The rats in the other three groups were trained, 60 minutes a day, 5 days per week, for 12 weeks. The maximum oxygen uptake test was conducted every 2 weeks, based on which the training load in the next 2 weeks was adjusted. The load intensity level in the main load period was defined as the percentage of maximum oxygen uptake (VO2max), which was 50%VO2max in the low intensity group, 65% VO2max in the middle intensity group and 80% VO2max in the high intensity group. Changes in bone density, bone structure and bone metabolism in each group were observed after exercise.

    RESULTS AND CONCLUSION: Compared with the quiet control group, there was a significant improvement in rat femoral density and whole body bone density in all the intensity groups after exercise (P < 0.05), and the high intensity group had better outcomes than the low intensity group and quiet control group (P < 0.01). There were significant differences in the low and middle intensity groups (P < 0.05) and extremely significant difference in the high intensity group (P < 0.01) before and after exercise. Compared with the quiet control group, trabecular bone area and levels of osteocalcin, alkaline phosphatase, and tartrate-resistant acid phosphatase in bone tissue and serum of rats were significantly improved in the low and middle intensity groups (P < 0.05) and dramatically improved in the high intensity group (P < 0.01) after exercise. Moreover, the improvement was more significant in the high intensity group than the low and middle intensity groups (P < 0.05). These findings indicate that different intensity endurance exercises can improve the bone density, bone structure and bone metabolism indexes in bone tissue and serum indexes of growing rats, and promote the bone growth of growing rats. The high-intensity endurance exercise has the best effect.

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    Duhuo Jisheng Decoction Disassembled Prescription inhibits chondrocyte inflammatory response  throughbased on Wnt/beta-catenin signaling pathway
    Li Hui, Ma Yuhuan, Xu Limei, Wang Shengjie, Xu Yunteng, He Xiaojuan, Jia Liangliang, Zeng Jianwei, Wang Lili, Li Xihai, Ye Hongzhi
    2020, 24 (35):  5589-5594.  doi: 10.3969/j.issn.2095-4344.2885
    Abstract ( 325 )   PDF (770KB) ( 85 )   Save

    BACKGROUND: ThePrevious studies have shown that the Wnt/β-catenin signaling pathway plays an important role in the pathogenesis and prognosis of chondrocyte inflammation, and the effective inhibition of chondrocyte inflammatory response byDuhuo Jisheng Decoction Disassembled Prescription remains to be further studied.

    OBJECTIVE: To investigate whether Duhuo Jisheng Decoction Disassembled Prescription can inhibit the inflammatory response of chondrocytes induced by lipopolysaccharide via the Wnt/β-catenin signaling pathway.
    METHODS: Male Sprague-Dawley rats were used to obtain knee joint chondrocytes by mechanical-type II collagenase digestion. The morphology and structure of chondrocytes were observed by inverted phase contrast microscope. Chondrocytes were identified by type II collagen immunohistochemistry. Duhuo Jisheng Decoction Disassembled Prescription with different mass concentrations (300, 400, 500 mg/L) was used to deal with the chondrocyte inflammation model induced by lipopolysaccharide (10 μg/L). After 8 hours of intervention, the ELISA method was used to determine the expression of interleukin-1β and tumor necrosis factor-α in the cell culture fluid to determine the intervention concentration of Duhuo Jisheng Decoction Disassembled Prescription. The second-generation chondrocytes were divided into four groups, followed by culture with normal medium in blank group, 10 μg/L lipopolysaccharide in model group, 10 μg/L lipopolysaccharide plus 400 mg/L Duhuo Jisheng Decoction Disassembled Prescription in 400 mg/L Duhuo Jisheng Decoction Disassembled Prescription group, and 10 μg/L lipopolysaccharide plus 10 mg/L Dickkopf-1 in inhibitor group. After 8 hours of intervention, the expression levels of β-catenin, Wnt-4, Frizzled-2, GSK-3β and CKI-ε were detected by western blot.
    RESULTS AND CONCLUSION: Chondrocyte identification results showed that the cytoplasm of chondrocytes was brown-yellow, with the typical characteristics of chondrocytes. ELISA results showed that the expression levels of interleukin-1β and tumor necrosis factor-α were higher in the model group than in the blank group, and the expression levels of interleukin-1β and tumor necrosis factor-α were significantly reduced in the 400 mg/L Duhuo Jisheng Decoction Disassembled Prescription group compared with the model group. Therefore, the intervention concentration of Duhuo Jisheng Decoction Disassembled Prescription was determined to be 400 mg/L. The results of western blot showed that the expression levels of Wnt-4, Frizzled-2, β-catenin and CKI-ε in the model group were higher than those in the blank group, whereas the expression of GSK-3β protein was lower than that in the blank group. The expression levels of Wnt-4, Frizzled-2, β-catenin and CKI-ε proteins in the Duhuo Jisheng Decoction Disassembled Prescription group and the inhibitor group were lower than those in the model group, whereas the protein expression level of GSK-3β was higher than that in the model group. All the findings indicate that Duhuo Jisheng Decoction Disassembled Prescription can inhibit lipopolysaccharide-induced chondrocyte inflammation by regulating the Wnt/β-catenin signaling pathway.

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    Platelet-rich plasma promotes the healing of tibial fracture in rabbits
    Ren Jun, Zhao Yan, Xiao Bin, Ma Chao, Wang Xinke, Hao Yabin, Cheng Jie
    2020, 24 (35):  5595-5599.  doi: 10.3969/j.issn.2095-4344.2882
    Abstract ( 353 )   PDF (556KB) ( 40 )   Save

    BACKGROUND: There are many questions about fracture healing, such as long self-healing cycles and delayed healing. Biological tissue has the potential for self-repair, so is there a way to mobilize the tissue’s self-repair ability for the organism’s self-repair? Platelet-rich plasma technology is one of the effective ways to solve this problem.

    OBJECTIVE: To study the effect of autologous platelet-rich plasmaon the healing of tibial fracture in rabbits.

    METHODS: Twelve New Zealand white rabbits were randomly divided into experimental group and control group, with six rabbits in each group. All animals were transversely fractured with a pendulum saw at a site of 2 cm distal to the right tibia, followed by fixation with Kirschner wire. In the experimental group, the platelet-rich plasma gel was injected into the fracture site, and in the control group the same amount of sterile saline was injected into the fracture site. Blood samples from rabbit models were taken before and at 2, 4, and 8 weeks after operation. The contents of osteocalcin and bone alkaline phosphatase were measured. Two rats from each group were killed at 2, 4, and 8 weeks after operation. Repair of fractures and volume of callus were observed and calculated, respectively.

    RESULTS AND CONCLUSION: The diameter of the callus in the experimental group was significantly larger than that of the control group at each observation time after operation (P < 0.05). Compared with the control group, the volume of the callus was significantly larger in the experimental group at 4 weeks postoperatively (P < 0.05), and still larger but not significantly at 8 weeks postoperatively (P > 0.05). The average width of trabecular bone, area ratio of trabecular bone and amount of blood vessels in the experimental group were better than those in the control group at 4 weeks postoperatively (P < 0.05); however, there was no significant difference between the two groups at 8 weeks postoperatively (P > 0.05). Serum osteocalcin in the two groups reached the highest level at 4 weeks postoperatively, and could keep a high level for a period of time. The peak level of serum osteocalcin in the experimental group was significantly higher than that in the control group (P < 0.05). The serum alkaline phosphatase level in the experimental group was always higher than that in the control group, indicating that platelet-rich plasma always has an effect on alkaline phosphatase level during fracture healing. To conclude, platelet-rich plasma has a certain promoting effect on the healing of tibial fracture, providing new ideas for treating fracture nonunion or delayed healing.

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    Hoxa9 silencing promotes tibial fracture healing by regulating osteogenic differentiation
    Zhang Chao, Li Xingyong, Ma Guifu, Pu Xingyu, Luo Wenyuan
    2020, 24 (35):  5600-5606.  doi: 10.3969/j.issn.2095-4344.2919
    Abstract ( 481 )   PDF (625KB) ( 51 )   Save

    BACKGROUND: Studies have shown that Hoxa10 gene has a certain correlation with osteogenic differentiation after microRNA regulation. However, the expression and function of Hoxa9 in osteogenic differentiation and tibial fracture healing have not been reported. 

    OBJECTIVE: To preliminarily investigate the effects of Hoxa9 on osteogenic differentiation of bone marrow mesenchymal stem cells in vitro and on fracture healing in an in vivo model.



    METHODS: In vitro experiment: In bone marrow mesenchymal stem cells cultured in osteogenic induction medium, Hoxa9 was inhibited by shHoxa9 or overexpressed by MSCV-Hoxa9. In vivo experiment: A tibial fracture model was constructed in rats, followed by intervention with Hoxa9 and shHoxa9.

    RESULTS AND CONCLUSION: In the in vitro test, qRT-PCR and western blot results indicated that Hoxa9 overexpression could significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (P < 0.05), downregulate osteogenesis-related gene markers osteocalcin, osteopontin, Runx2 and collagen type I at mRNA and protein levels (P < 0.05), and reduce the number of calcified nodules, osteogenic differentiation ability and alkaline phosphatase activity (P < 0.05). In contrast, transfection of BMSCs with silenced Hoxa9 gene could reverse the above indicators. In the in vivo test, histological staining results showed that Hoxa9 intervention significantly aggravated bone damage in rats, and no interstitial collagen fibers and cartilage in the callus were found. The rats intervened by shHoxa9 showed a significant increase in bone size and number, and inter-tissue collagen fibers and cartilage in callus were detected. Findings from qRT-PCR and western blot in the in vivo test showed that the mRNA and protein expression of osteocalcin, osteopontin, Runx2 and collagen type I were significantly down-regulated in the Hoxa9 group (P < 0.05), and up-regulated in the shHoxa9 group (P < 0.05). In summary, Hoxa9 silencing may promote osteogenic differentiation of bone marrow mesenchymal stem cells and thereby promote fracture healing. 

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    Inhibitory effects of different doses of genistein on joint pain and inflammation in osteoarthritis model rats
    Zeng Xiaoyun, Zhang Lirong
    2020, 24 (35):  5607-5612.  doi: 10.3969/j.issn.2095-4344.2920
    Abstract ( 504 )   PDF (613KB) ( 41 )   Save

    BACKGROUND: Genistein is a soy product derivative that can prevent osteoporosis and inhibit cancer. There is no relevant report on its role in osteoarthritis.

    OBJECTIVE: To study the effects of different doses of genistein on osteoarthritis and to explore its mechanism.

    METHODS: A model of right knee osteoarthritis was established in male Wistar rats by using papain method. The experiment was divided into five groups: low, medium and high dose groups were administered with 4.5, 9, and 18 mg/(kg•d) genistein, respectively; a positive control group was given 15 mg/(kg•d) diclofenac sodium by gavage; and a control group was given pure water. Administration in each group was kept for 35 continuous days. The knee joint diameter of the right knee was measured on the 7th, 14th, and 21st day after administration. At the 1st, 3rd, and 5th week after administration, the levels of inflammatory factors in the right knee joint fluid were measured. Pure water, genistein colloid and 0.8% formaldehyde were separately applied to the skin surface of male Wistar rats to establish a skin irritation model. Redness and rash on the skin were then observed. The painful tumbling model of male Wistar rats was established by acetic acid method. The intervention method was the same as the knee osteoarthritis model. The number of limb tumbling in the rats within the first and the last 20 minutes was recorded to assess the analgesic effect. Ethic approval was obtained from the Animal Experiment Ethics Committee of Southern Medical University.

    RESULTS AND CONCLUSION: At the same time point, the knee joint diameter of the middle and high dose groups and the positive control group was smaller than that of the control group (P < 0.05), and there was no significant difference between the first three groups (P > 0.05). At the same time point, the levels of matrix metalloproteinase-3, interleukin-6 and interleukin-1β were lower in the middle and high dose groups and the positive control group than in the control group (P < 0.05), and there was no significant difference between the first three groups (P > 0.05). Genistein gel did not result in induce rash and redness on the surface of the rat skin. In the first and the last 20 minutes, 9 and 18 mg/kg genistein could alleviate pain in rats, and its analgesic effect was similar to that of diclofenac sodium. All these findings indicate that genistein is not irritating to the skin and within a certain dose range, genistein can relieve pain and have anti-inflammatory, anti-swelling and anti-osteoarthritis effects.

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    Isoliquiritigenin inhibits SETD7 expression against oxidative damage in cardiomyocytes induced by hypoxia/reoxygenation
    Yu Hui, Zhao Yang, Fei Jiayue, Zhang Wenli, Zhao Luosha
    2020, 24 (35):  5613-5618.  doi: 10.3969/j.issn.2095-4344.2353
    Abstract ( 337 )   PDF (580KB) ( 63 )   Save

    BACKGROUND: Ischemic heart disease has become one of the important diseases that threaten human health, but the molecular mechanism of its occurrence and development has not yet been elucidated.

    OBJECTIVE: To investigate the effects of isoliquiritigenin (ISL) on oxidative stress and apoptosis in cardiomyocytes after hypoxia/reoxygenation (H/R) injury and its possible mechanism.

    METHODS: Rat cardiomyocytes H9C2 were cultured in vitro and randomly divided into normal control group, H/R group, H/R+ISL 10, 20, 40, 80 μmol/L groups, H/R+si-con group, H/R+si-SETD7 group, H/R+ISL+pcDNA group, H/R+ISL+pcDNA-SETD7 group. Cell viability was measured using methylthiazolyl tetrazolium (MTT) assay. Apoptosis was detected by flow cytometry. The levels of reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in the cells were measured. The expression of apoptosis-related protein Cleaved Caspase-3 was detected by western blot assay.

    RESULTS AND CONCLUSION: Compared with the normal control group, the cell survival rate of H/R group was significantly decreased (P < 0.05), the apoptosis rate was significantly increased (P < 0.05), Cleaved caspase-3 expression and ROS and MDA levels were significantly increased (P < 0.05), while the GSH-Px content was significantly reduced (P < 0.05). Compared with the H/R group, the cell survival rate of H/R+ISL 10, 20, 40, 80 μmol/L groups was significantly increased (P < 0.05), and the apoptosis rate was significantly decreased (P < 0.05), and the expression of SETD7 and Cleaved caspase-3 was significantly decreased (P < 0.05), and the levels of ROS and MDA were significantly decreased (P < 0.05), while the content of GSH-Px was significantly increased (P < 0.05). Compared with the H/R+si-con group, the cell survival rate of H/R+si-SETD7 group was significantly increased (P < 0.05), the apoptosis rate was significantly decreased (P < 0.05), the expression of SETD7 and Cleaved caspase-3 was significantly decreased (P < 0.05), and the levels of ROS and MDA were significantly decreased (P < 0.05), while the content of GSH-Px was significantly increased (P < 0.05). Compared with the H/R+ISL+pcDNA group, the cell survival rate of H/R+ISL+pcDNA-SETD7 group was significantly decreased (P < 0.05), the apoptosis rate was significantly increased (P < 0.05), the expression of SETD7 and Cleaved caspase-3 was significantly increased (P < 0.05), and the levels of ROS and MDA were significantly increased (P < 0.05), while the content of GSH-Px was significantly decreased (P < 0.05). These findings indicate that ISL can inhibit the expression of SETD7 to reduce the apoptosis of cardiomyocytes induced by H/R and enhance the cell antioxidant capacity, thereby protecting cardiomyocytes against H/R injury.

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    Autophagy has an early protective effect against fibroblast injury induced by advanced glycation end products
    Han Yanfu, Tao Ran, Sun Tianjun
    2020, 24 (35):  5619-5624.  doi: 10.3969/j.issn.2095-4344.2921
    Abstract ( 457 )   PDF (26119KB) ( 64 )   Save

    BACKGROUND: Advanced glycation end products (AGEs) are closely related to diabetic wound healing. AGEs can affect the proliferation and migration of fibroblasts, but the early protective effect of autophagy in AGE-induced fibroblast injury has not been explored.

    OBJECTIVE: To confirm the effect of AGEs on fibroblast cell viability and autophagy, and to explore the early protective effect of autophagy on cell injury.

    METHODS: Human fibroblasts were cultured in vitro. Normal control group (DMEM medium), AGE group (DMEM medium+100 mg/L AGEs), AGE+PTB (AGE inhibitor) group (DMEM medium+100 mg/L AGEs+100 mg/L PTB), and AGE+chloroquine (autophagy inhibitor) group (DMEM medium+100 mg/L AGEs+10 μmol/L chloroquine) were established. After 48 hours of culture, trypan blue staining was used to detect the cell viability of each group, western blot was used to detect the expression of LC3 and P62 protein, cell immunofluorescence assay was used to detect the formation of autophagy using, and transmission electron microscopy was used to observe the ultrastructure of autophagy vesicles.

    RESULTS AND CONCLUSION: Compared with the control group, cell death rate in the AGE group increased significantly (P < 0.01). Compared with the AGE group, the cell death rate in the AGE+PTB group decreased significantly (P < 0.05), while that in the AGE+chloroquine group increased significantly (P < 0.05). Compared with the control group, the ratio of LC3 II/LC3 I in the AGE group increased significantly, and the expression of P 62 decreased significantly (P < 0.01); compared with the AGE group, the ratio of LC3 II/LC3 I in the AGE+PTB group decreased significantly, the expression of P62 increased significantly (P < 0.05), whereas the content of LC3 II/LC3 I in the AGE+chloroquine group did not change significantly (P > 0.05) and the expression of P62 increased significantly (P < 0.05). Both in the AGE group and AGE+chloroquine group, the green fluorescent dot-like aggregation of LC3 was increased. By comparing these two groups, there were more autophagy bodies and autophagy vesicles in the AGE group, whereas the number of autophagy structures and vacuole like structures were less in the AGE+chloroquine group. These findings indicate that AGEs could damage fibroblasts in vitro, reduce cell survival rate, and activate autophagy activity in an early stage, and moreover induced autophagy could certainly protect fibroblasts.

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    Pathological and behavioral changes after ischemic stroke in adult mice
    Liang Yanfeng, Hao Peng, Duan Hongmei, Zhao Wen, Gao Yudan, Li Xiaoguang, Yang Chaoyang
    2020, 24 (35):  5625-5631.  doi: 10.3969/j.issn.2095-4344.2922
    Abstract ( 591 )   PDF (546KB) ( 312 )   Save

    BACKGROUND: A rat model of middle cerebral artery embolization can cause stable focal cortical infarction, and it has a low mortality rate while simulating the pathological state of human stroke. However, there are high requirements on the skills and equipment and a later evaluation is necessary to determine the success of modeling.

    OBJECTIVE: To establish an effective, stable and simple ischemic stroke model, to reveal pathological changes in infarcted and surrounding areas after stroke in mice, and to explore behavioral changes after stroke in mice.

    METHODS: Permanent electrocoagulation of the distal middle cerebral artery in mice was condcted. Twenty-four hours later, 2,3,5-triphenyltetrazolium chloride staining was used to determine the infarct size of the model and to calculate the success rate of the model. Hematoxylin-eosin staining was performed on brain tissue sections at different time points (1, 3, 7, 10, 14 days) after occlusion of the distal middle cerebral artery in mice to observe volume changes of the ischemic necrosis area with time. Immunohistochemical staining of glial fibrillary acidic protein and Iba-1 was performed to detect the changes of glial reaction and inflammatory reaction after brain injury in model mice. Finally, grid foot error test and cylinder test were used to evaluate the loss of sensorimotor function after stroke.

    RESULTS AND CONCLUSION: Focal cortical infarction was caused after distal middle cerebral artery occlusion. The mortality rate of this new model was only 9% and the success rate was 87%. Infarction was mainly located in M1/S1/S2 area, and the infarcted range was stable after 10 days of occlusion. The inflammatory response peaked on the 3rd day of stroke, and a stable astroglial scar was formed around the injury area on the 14th day. After focal cortical infarction, the contralateral limbs of mice showed obvious loss of sensory and motor functions. To conclude, sensory and motor functions deficits occur immediately after stroke in experimental mice and persist until 12 weeks after stroke. The new model of distal middle cerebral artery occlusion is a stable, reliable model, with a clear infarct range, which is suitable for the study of ischemic stroke.


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    Involvement of miR-148a-5p in ApoE-/- mouse hepatocyte apoptosis induced by high methionine diet
    Ma Fang, Zhang Hui, Li Guizhong, Ma Shengchao, Shen Jiangyong, Sun Lei, Hao Yinju, Ma Shengxian, Jiang Yideng
    2020, 24 (35):  5632-5637.  doi: 10.3969/j.issn.2095-4344.2349
    Abstract ( 521 )   PDF (519KB) ( 86 )   Save

    BACKGROUND: High methionine diet can cause liver damage in ApoE-/-mice, and microRNAs (miRNAs) are involved in various cell processes such as cell survival, differentiation, and apoptosis, which is of great significance.

    OBJECTIVE: To investigate the effect of miR-148a-5p on ApoE-/- mouse hepatocyte apoptosis induced by high methionine diet.

    METHODS: Twelve ApoE-/- mice aged 5 weeks were randomly divided into two groups with six ApoE-/- mice in each group: ApoE-/- control group was fed with a normal diet, and ApoE-/- high methionine diet group (ApoE-/-+HMD) was fed with a high methionine diet. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissues in the two groups. TUNEL staining was used to observe the apoptosis of hepatocytes. The expressions of Bax and Bcl-2 were detected by western blot. Fluorescence quantitative PCR was used to detect the expression of miR-148a-5p. Target Scan prediction software was used to predict the target gene of miR-148a-5p, and double luciferase activity assay was used to verify the targeted relationship.

    RESULTS AND CONCLUSION: Compared with the control group, the hepatic lobular structure of the ApoE-/- mice with high methionine diet was obviously disturbed, and some cells showed cytoplasmic osteoporosis; hepatocyte apoptosis increased; the expression of Bax significantly increased and the expression of Bcl-2 significantly decreased (P < 0.01). Fluorescence quantitative PCR results showed that the expression of miR-148a-5p increased in the ApoE-/- mice with high methionine diet (P < 0.05). The target gene prediction software indicated that Bcl-2 was a potential target gene of miR-148a-5p, and the targeted relationship between miR-148a-5p and Bcl-2 was confirmed by the double luciferase activity assay (P < 0.05). After miR-148a-5p was overexpressed in hepatocytes, Bax expression increased and Bcl-2 expression decreased significantly (P < 0.01). In conclusion, miR-148a-5p promoted hepatocyte apoptosis through negative regulation of Bcl-2 in ApoE-/- mouse hepatocytes induced by high methionine diet, which may be one of the mechanisms causing liver injury.

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    Mechanism of Qutan Zhuyu Decoction for osteonecrosis of the femoral head based on network pharmacology
    Fan Yinuo, Chen Minghai, Li Weifeng, Chen Lixin, Wei Qiushi, He Wei, Chen Zhenqiu
    2020, 24 (35):  5638-5643.  doi: 10.3969/j.issn.2095-4344.2875
    Abstract ( 439 )   PDF (526KB) ( 110 )   Save

    BACKGROUND: Traditional Chinese medicine believes that the early bone erosions mostly belong to phlegm and blood stasis, so early treatment of osteonecrosis of the femoral head (ONFH) is often similar to the treatment of phlegm and blood stasis. Based on network pharmacology we can build a “component-target- pathway-disease” network of drugs to explore the relationship between drugs and diseases, thereby clarifying the mechanism of drugs

    OBJECTIVE: To construct the component-target-pathway-disease network of Qutan Zhuyu Decoction and to explore the key targets and mechanism of Qutan Zhuyu Decoction in the treatment of ONFH.

    METHODS: Taohong Siwu Decoction and Erchen Decoction are effective prescriptions for the treatment of early ONFH. The representative drugs include Pinellia tangerine peel, medlar, peach kernel and safflower, named as Qutan Zhuyu Decoction. The main active components and targets of Qutan Zhuyu Decoction was searched and screened in the Chinese Medicine Computing System Pharmacology Analysis Platform (TCMSP), and a search for ONFH targets in the Human Gene Database (GeneCards) and the Human Mendelian Genetic Database (OMIM) was performed. The common targets of Qutan Zhuyu Decoction and ONFH were got by Venn diagrams. Cytoscape3.6.1 was used to construct a Chinese medicine-ingredient-disease-target regulation network, then establish a protein-protein interaction network through the STRING data platform, and finally use the Bioconductor platform and R language for gene ontology enrichment analysis and gene interaction (KEGG) pathway analysis.

    RESULTS AND CONCLUSION: The main components of Qutan Zhuyu Decoction for the treatment of ONFH were 78 active components such as sitosterol and naringenin. The targets for therapeutic effects might include 61 key targets such as NCOA2 and PTGS1. The biological processes affecting the treatment of ONFH mainly included proximal promoters, sequence-specific DNA binding, and regulation of DNA-binding transcriptional activity. Key pathways for therapeutic use included interleukin-17 signaling pathway and apoptosis. Overall, the therapeutic effect of Qutan Zhuyu Decoction on ONFH reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine, suggesting that its mechanism may be achieved by multi-components, multi-targets and multi-channels.

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    Clinical study on the relationship between critical shoulder joint angle and degenerative rotator cuff tear
    Huo Yanxu, Yang Zhi, Pei Fang, Chen Xiangyang
    2020, 24 (35):  5644-5649.  doi: 10.3969/j.issn.2095-4344.2923
    Abstract ( 466 )   PDF (456KB) ( 50 )   Save

    BACKGROUND: The anatomical structure of the shoulder blade is related to the occurrence of a rotator cuff tear, and critical shoulder angle (CSA) can reflect the individual anatomical differences of the shoulder blade. In recent years, studies have found that CSA is a risk factor for rotator cuff tear; however, its diagnostic value for rotator cuff tear in Chinese population still needs further research.

    OBJECTIVE: To analyze whether CSA is a risk factor for rotator cuff tear in Chinese people, and to explore the risk level of CSA in degenerative rotator cuff tear in comparison with acromion index (AI) and glenoid inclination.

    METHODS: Thirty-two patients who had been diagnosed with rotator cuff tear from January 2016 to December 2018 were collected as the tear group, including 17 males and 15 females, aged 37-75 years, with an average age of (54.7±9.2) years. Meanwhile, another 34 patients without rotator cuff tear were selected as the control group, including 19 males and 15 females, aged from 35 to 91 years, with an average (53.6±11.8) years. The CSA, AI and β angle of the glenoid cavity were compared between two groups. Correlation analysis and receiver operating characteristic curve analysis were performed for each parameter to determine the cutoff value and the area under the curve.

    RESULTS AND CONCLUSION: The mean CSA and AI of the tear group were significantly higher than those of the control group (37.4° vs. 34.1°, P < 0.001; 0.72 vs. 0.68, P=0.007). However, there was no significant difference between the tear group and the control group in the β angle of the glenoid cavity and age (P > 0.05). In the correlation analysis, only CSA showed a high positive correlation with AI among all parameters (r=0.848, P < 0.001), whereas there was no correlation between the other parameters (P > 0.05). In the receiver operating characteristic curve analysis, the area under the curve of CSA and AI was 0.752 and 0.663, respectively, with cut-off values of 37.5 and 0.72. To conclude, It may be a risk factor of degenerative rotator cuff tear for Chinese people, and it has a higher risk level of degenerative rotator cuff tear than the acromion index.

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    Triptolide improves spinal cord injury recovery via upregulation of autophagy and inhibition of apoptosis in Thy-YFP transgenic mice
    Zhu Ning, Yang Xinming, Ruan Jianwei
    2020, 24 (35):  5650-5655.  doi: 10.3969/j.issn.2095-4344.2886
    Abstract ( 369 )   PDF (610KB) ( 198 )   Save

    BACKGROUND: Studies have shown that treatment with triptolide reduces ischemic lesion area, water

    content, and nerve cell death in a rat model of stroke. In addition, triptolide can promote the repair of spinal cord injury by inhibiting astrocyte hyperplasia, microglia activation and inflammatory response.

    OBJECTIVE: To investigate the effect of triptolide on the autophagy and apoptosis in the spinal cord of Thy-YFP transgenic mice after spinal cord injury.

    METHODS: Sixty Thy-YFP transgenic mice were randomly divided into four groups: sham, dimethyl sulfoxide (DMSO), triptolide and methylprednisolone groups. Following the establishment of the spinal cord injury models, mice in the triptolide, DMSO and sham group were immediately intraperitoneally injected with triptolide (0.2 mg/kg·d) or 5% DMSO-normal saline solution (0.2 mg/kg·d) for 7 days, whereas mice in the methylprednisolone group were intraperitoneally injected with methylprednisolone (30 mg/kg) at 30 minutes, 6 hours and 24 hours after surgery. Basso Mouse Scale was used to assess the recovery of motor function; hematoxylin-eosin staining and Nissl staining were used to explore tissue recovery after spinal cord injury; western blot and immunofluorescence staining were employed to assess the levels of autophagy-associated proteins, Beclin-1, LC3B, p62, and apoptosis-associated proteins, Bcl-2, Bax and caspase-3. An ethic approval for animal experiments was obtained from Hebei North University with an approval No. W20200002.

    RESULTS AND CONCLUSION: Treatments with triptolide or methylprednisolone after spinal cord injury significantly improved motor function and reduced neuronal cell death. In addition, the expression of autophagy-associated protein LC3B was upregulated and the expression of p62 was downregulated following triptolide treatment; the expressions of apoptosis-associated proteins caspase-3 and Bax were reduced, while the expression of anti-apoptosis protein Bcl-2 was increased after triptolide treatment. To conclude, triptolide improves the motor function after spinal cord injury, which is related to upregulation of autophagy and inhibition of apoptosis. Triptolide may be a potential neuroprotective agent for spinal cord injury.

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    Immunostimulation combined with liquid nitrogen freezing to construct a rat model of atherosclerotic vulnerable plaque
    Wei Gang, Gao Shangyuan, Zhang Ying, Huang Weiyi
    2020, 24 (35):  5656-5661.  doi: 10.3969/j.issn.2095-4344.2924
    Abstract ( 272 )   PDF (529KB) ( 45 )   Save

    BACKGROUND: Vulnerable plaque is the pathological basis of acute cardiac and cerebrovascular ischemic events. Establishing a suitable animal vulnerable plaque model is of great significance for guiding the prevention and treatment of cardiovascular and cerebrovascular diseases. However, there is no well-established method for constructing the vulnerable plaque model.

    OBJECTIVE: To investigate whether immunostimulation can cooperate with liquid nitrogen freezing to establish an atherosclerotic vulnerable plaque model in rats, aiming to replicate the widely applicable atherosclerotic model.

    METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups after 1 week of adaptive feeding, namely, control group, high-fat group, liquid nitrogen group, immunostimulation + liquid nitrogen group. After 2 weeks of conventional diet and special high-fat diet, respectively, the rats in the control group and the other groups were given a single dose of vitamin D3 injection through the abdominal cavity. Rats in the control and high-fat diet groups were subjected to sham operation with no immunostimulation and liquid nitrogen freezing, and given routine diet and special high-fat diet for 10 weeks respectively. Rats in the liquid nitrogen group and immunostimulation + liquid nitrogen group were given liquid nitrogen freezing, followed by 10 weeks of high-fat diet. During this period, the rats in the immunostimulation + liquid nitrogen group were given subcutaneous injection of bovine serum albumin (3 times per week, for 3 weeks) and intraperitoneal injection of ovalbumin (3 days interval, 5 times in total). At 10 weeks after modeling, blood samples were taken to detect blood lipid index, inflammation and oxidative stress injury index, and heme oxygenase-1 (HO-1) protein expression in rats. The target blood vessel segments of each group were executed for hematoxylin-eosin staining, and the pathological changes of atherosclerotic plaques were observed under light microscopy. The study protocol was approved by the Animal Ethics Committee of Southwest Medical University, with an approval No. IACUC:20170917006.

    RESULTS AND CONCLUSION: Compared with the control group, there were no significant changes in cholesterol level, inflammatory and oxidative stress index, HO-1 protein expression and histopathological examination in the high-fat group (P > 0.05). Compared with the control and high-fat groups, the levels of serum lipids, inflammatory and oxidative stress indicators and HO-1 protein expression in the liquid nitrogen and immunostimulation + liquid nitrogen groups were significantly increased (P < 0.05). Histopathological examination also indicated that there were obvious plaques, and the increasing trend in the immunostimulation + liquid nitrogen group was more significant (P < 0.05). Compared with the liquid nitrogen group, the levels of serum lipids, inflammatory and oxidative stress indexes and HO-1 protein expression in the immunostimulation + liquid nitrogen group were significantly increased (P < 0.05), and histopathological examination also showed more obvious atherosclerotic plaques. Therefore, immunostimulation could accelerate the formation of rat common carotid atherosclerotic vulnerable plaque model in cooperation with liquid nitrogen freezing injury, which lays a foundation for the intervention experiment of atherosclerotic disease.

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    Mechanism by which allicin inhibits proliferation and migration but promotes apoptosis of human fibroblasts
    Zhu Shoulei, Yang Jiandong, Cai Jun, Zhang Yujie, Tian Yuan
    2020, 24 (35):  5662-5667.  doi: 10.3969/j.issn.2095-4344.2354
    Abstract ( 387 )   PDF (560KB) ( 187 )   Save

    BACKGROUND: Allicin has an anti-fibrosis effect and can inhibit the proliferation and collagen synthesis of hyperproliferation of fibroblasts, but the exact mechanism of allicin inhibiting the proliferation and inducing the apoptosis of fibroblasts remains unclear.

    OBJECTIVE: To explore the mechanism of allicin inhibiting proliferation, migration and promoting apoptosis of human fibroblasts, providing new ideas for prevention and treatment of epidural adhesions.

    METHODS: Logarithmic fibroblasts from human epidural scar were treated by allicin at a gradient of concentration for 24 hours. Cell morphology was observed using a fluorescence microscope. Cell counting kit-8 assay, scratch assay and flow cytometry were used to measure cell proliferation, migration and apoptosis, respectively, while western blot and real-time quantitative PCR were used to measure the expression levels of proliferating cell nuclear antigen, Bcl-2 and Bax related to cell proliferation and apoptosis.

    RESULTS AND CONCLUSION: After treated by allicin for 2 hours, the fibroblasts shrunk, deformed and became smaller in size. Their nuclei were retracted and fragmented. Cell viability and migration rate decreased significantly in a dose-dependent manner (P < 0.01). The percentage of G1 phase cells significantly increased (P < 0.01), while that of S phase and G2 phase cells significantly decreased in a dose-dependent manner (P < 0.01). Similarly, the percentage of apoptotic cells increased significantly in a dose-dependent manner (P < 0.01). Compared with control group, the expression levels of proliferating cell nuclear antigen and Bcl-2 significantly decreased (P < 0.01), while the Bax level significantly increased (P < 0.01). Findings from this study indicate that allicin can inhibit the human fibroblast proliferation, migration and induce its apoptosis, possibly by regulating the expression of proliferating cell nuclear antigen, Bcl-2 and Bax.

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    Molecular mechanism of tortoise plastron-deer horn couplet medicine in the treatment of osteoporosis based on network pharmacology approach
    Li Shaoshuo, Gu Yidan, Yin Heng, Guo Yang, Ma Yong, Wang Jianwei
    2020, 24 (35):  5668-5674.  doi: 10.3969/j.issn.2095-4344.2925
    Abstract ( 480 )   PDF (562KB) ( 240 )   Save

    BACKGROUND: The tortoise plastron-deer horn couplet medicine has been widely used as a classic drug matching formula for treatment of osteoporosis, but the pharmacology molecular mechanism remains unclear.

    OBJECTIVE: To investigate the pharmacological molecular mechanism of tortoise plastron-deer horn couplet medicine for treatment of osteoporosis.

    METHODS: The active compounds and targets of tortoise plastron-deer horn couplet medicine were obtained by using BATMAN-TCM, TCM-MESH and Chemistry Databases, as well as manual literature retrieval. The disease targets corresponding to osteoporosis were obtained by using Comparative Toxicogenomics Database and GeneCards databases. The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. Gene ontology analysis of the targets was conducted by DAVID online tools. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was conducted by KOBAS. The enrichment results were obtained with a significant difference (P < 0.05). SwissDock was used for molecular docking verification of hub targets and active compounds.

    RESULTS AND CONCLUSION: A total of 21 active ingredients (including aspartic acid and phenylalanine) and 183 targets of tortoise plastron-deer horn couplet medicine for treatment of osteoporosis were obtained. There was a close interaction among herb pairs, active compounds and targets. Ten hub targets, such as INS, ALB and TNF, were sorted. Hub targets were mainly enriched in 66 gene ontology processes, such as aging and drug reaction. KEGG analysis showed 27 enrichment pathways of the targets with significant difference. Molecular docking results showed that HUB gene INS and ALB could be effectively combined with their corresponding active compounds (INS: alanine, androgens; ALB: alanine). These findings preliminarily validate the major compounds, targets and pathways of tortoise plastron-deer horn couplet medicine for treatment of osteoporosis. The medicine-compounds-targets network is complicated. The mechanism may happen through multiple closed pathways including cell differentiation, inflammatory response and sex hormone regulation as well as regulating dynamic balance of bone repair and remodeling. It is worth further investigating for the mechanism of Chinese medicine treating diseases.

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    Efficacy of free fibula transplantation combined with platelet rich plasma in the treatment of early necrosis of the femoral head
    Mo Fan, Hua Qikai, Zhao Jinmin, Sha Ke, Xie Qi, Zhang Jin, Yang Yuan, Huang Weifeng, Wang Hao, Huang Hao, Chen Yinghua
    2020, 24 (35):  5675-5681.  doi: 10.3969/j.issn.2095-4344.2926
    Abstract ( 359 )   PDF (563KB) ( 89 )   Save

    BACKGROUND: Autologous platelet-rich plasma is a platelet concentrate obtained by centrifugation of autologous whole blood. Studies have proved that autologous platelet-rich plasma can promote bone and cartilage repair, tissue repair, and vascular regeneration, and it is widely used in various disciplines such as stomatology, orthopedics, sports medicine, plastic cosmetology and dermatology.

    OBJECTIVE: To observe and discuss the clinical effect of free fibular transplantation combined with autologous platelet-rich plasma in the treatment of avascular necrosis of the femoral head in young adults.

    METHODS: From May 2014 to August 2018, 20 patients (24 hips) with early avascular necrosis of the femoral head in young adults were subjected to curettage of femoral head necrosis focus and free fibular transplantation with vascular anastomosis and platelet-rich plasma. Harris score system was used for evaluation at 12 months after operation to calculate the excellent and good rate and improvement rate of affected hips. Curative effect evaluation, imaging changes, follow-up results and complications of patients were recorded before and after operation.

    RESULTS AND CONCLUSION: All 20 patients (24 hips) were followed up as scheduled. The follow-up time after operation was 1.0-2.5 years, with an average of 1.35 years. Harris score was used to evaluate curative effects, with excellent in 12 hips, good in 10 hips, fair in 1 hip, poor in 1 hip, and an excellent and good rate of 91.7%. There was a significant difference in the Harris score of the affected hip before operation and 12 months after operation (P=0.000). During the 12-month follow-up after the operation, 3 hips still had pain, 2 hips had imaging progress. Improvement grade was in 17 hips, unchanged grade in 5 hips, failure grade in 2 hips, with the improvement rate of 91.7%, and the clinical symptoms and signs of the patients were consistent with the imaging performance progress. Three patients (four hips) experienced numbness in the anterolateral thigh of the same side after operation, and completely recovered to normal after 3 months. One patient (one hip) underwent hip replacement 18 months after operation for avascular necrosis of femoral head (ARCO stage IV). No complications such as incision nonunion, infection and venous thrombosis were found. These results indicate that the anastomosed fibular graft combined with autologous platelet-rich plasma has good short-term clinical effect and high excellent rate in the treatment of early avascular necrosis of the femoral head.

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    Designing modified blocks based on Action Research Arm Test: evaluating the recovery potential of upper limb function in stroke patients
    Shao Danli, Xu Xuedi, Gao Xiaoping, Zhang Xu
    2020, 24 (35):  5682-5687.  doi: 10.3969/j.issn.2095-4344.2927
    Abstract ( 347 )   PDF (491KB) ( 54 )   Save

    BACKGROUND: Action research arm test has advantage in assessment of movement function in stroke patients, especially in complex upper limbs; however, its use is restricted due to the complicated and heavy evaluation tools.

    OBJECTIVE: To explore the advantages of the modified blocks of Action Research Arm Test.

    METHODS: Forty patients who firstly suffered from stroke within 1 month with Brunnstrom stage III for affected hands were selected. According to whether the patient could grasp larger modified block without counterweight, enrolled patients were divided into a control group (n=20) and an experimental group (n=20). All patients received routine rehabilitation for 4 weeks. The Action Research Arm Test and the grasp subscale were used to assess the motor function of the hemiplegic upper limbs before and after rehabilitation. The Brunnstrom stage for hand was recorded after 4-week rehabilitation. The study protocol was approved by the Medical Ethics Committee of First Affiliated Hospital of Anhui Medical University and all patients signed the consent form.

    RESULTS AND CONCLUSION: Findings from independent sample t-test between the two groups showed that there was no statistical difference in the scores of Action Research Arm Test and grasp subscale between two groups before enrollment (P=0.692, 0.521), whereas the scores of Action Research Arm Test and grasp subscale were significantly higher in the experimental group than the control group after 4-week rehabilitation (P=0.008, 0.001). Findings from the paired sample t-test showed that the scores of Action Research Arm Test and grasp subscale after 4-week rehabilitation were significantly higher than those before treatment (P < 0.001). Results of the intragroup chi-square test showed that the Brunnstrom stage for affected hands indicated better recovery in the experimental group than the control group (χ2=4.80, P < 0.05). All these findings reveal that the modified blocks with suitable counterweights can replace the original wooded cubes when using the Action Research Arm Test. The modified block can be used to refine the grasp subscale. The recovery potential of patients can be roughly distinguished according to whether the patients can grasp the larger modified block without counterweight.

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    Effects of dexmedetomidine on perioperative brain protection in patients undergoing craniocerebral surgery under inhalation anesthesia with sevoflurane: a randomized controlled study
    Liu Yongpan, Gong Xiaofang
    2020, 24 (35):  5688-5694.  doi: 10.3969/j.issn.2095-4344.2928
    Abstract ( 348 )   PDF (671KB) ( 222 )   Save

    BACKGROUND: The inhalational anesthetic sevoflurane is often used in craniocerebral surgery for its advantages of quick onset, stable circulation, high safety, and few adverse reactions. However, it can also lead to abnormal blood pressure and heart rate, as well as restlessness and pain. Therefore, an auxiliary anesthetic is needed to help reduce adverse reactions. Dexmedetomidine is a potent and highly selective α2 adrenergic receptor agonist that has anti-anxiety, hypnotic, analgesic, sedative, and sympatholytic properties. Dexmedetomidine has been shown to reduce restlessness after sevoflurane inhalation anesthesia and minimize perioperative hemodynamic fluctuation. However, its application in craniocerebral surgery should be validated.

    OBJECTIVE: To investigate the efficacy of dexmedetomidine in craniocerebral surgery under sevoflurane inhalation anesthesia.

    METHODS: The prospective, single-center, randomized, controlled study will be performed in Taihe Hospital (Shiyan, China). The 1308 patients to be included in this study will be randomly divided into a trial group and control group (n=654 patients per group) based on a table of random permutations. In both groups, sevoflurane will be used for induction of anesthesia for craniocerebral surgery. In the trial group, 1 μg/kg dexmedetomidine will be injected intravenously for 10 minutes commencing 15 minutes before anesthesia induction, and then continuously pumped at 0.3 μg/kg per hour until 30 minutes before surgery. In the control group, 0.9% sodium chloride injection will be administered in the same way and at the same injection rate. This trial was approved by the Ethics Review Committee of Taihe Hospital on December 8, 2015 (Approval No. 2015GJJ-087). Participants will not be blind to the study protocol or procedure, and will provide signed informed consent. This study was registered with Chinese Clinical Trial Registry on March 2, 2020 (registration No. ChiCTR2000030459). Protocol version: 1.0.

    RESULTS AND CONCLUSION: The primary outcome of this study is recovery time. Secondary outcomes of this study include anesthesia, recovery, and adverse events, as well as vital signs, stress index, and cerebral metabolic rate of oxygen consumption at different time points (before and after administration of the loading dose of dexmedetomidine, during anesthesia induction, at the beginning of craniocerebral surgery, during craniocerebral surgery, at the end of craniocerebral surgery, and at the time of recovery). A pilot study involving 190 patients who underwent craniocerebral surgery was performed between March 2016 and February 2017. These 190 patients randomly received either sevoflurane anesthesia (n=95, control group) or dexmedetomidine and sevoflurane anesthesia (n=95, trial group). Results of the pilot group showed that anesthesia time, intraoperative bleeding volume, intraoperative infusion volume, recovery time, and extubation time were similar between trial and control groups (P > 0.05). However, compared with the control group, the administered dosages of vasoactive drugs ephedrine and esmolol were significantly lower (P < 0.05) in the trial group. Heart rate and electroencephalography bispectral index after administration of the loading dose of dexmedetomidine, during anesthesia induction, at the beginning of craniocerebral surgery, during craniocerebral surgery, at the end of craniocerebral surgery, and at the time of recovery were significantly higher in the trial group compared with the control group (P < 0.05). At the beginning of craniocerebral surgery, during craniocerebral surgery, at the end of craniocerebral surgery, and at the time of recovery, mean arterial pressure in the trial group was significantly higher compared with the control group (P < 0.05). After administration of the loading dose of dexmedetomidine, during anesthesia induction, at the beginning of craniocerebral surgery, during craniocerebral surgery, at the end of craniocerebral surgery, and at the time of recovery, blood glucose level in the trial group was significantly higher compared with the control group (P < 0.05). After administration of the loading dose of dexmedetomidine, during anesthesia induction, and at the beginning of craniocerebral surgery, cortisol concentrations in the trial group were significantly lower compared with the control group (P < 0.05). During craniocerebral surgery, at the end of craniocerebral surgery, and at the time of recovery, jugular bulb venous blood oxygen saturation, difference in oxygen content between arterial and jugular venous blood, and cerebral metabolic rate of oxygen consumption in the trial group were significantly higher compared with the control group (P < 0.05). Findings from this study will help determine whether dexmedetomidine can reduce hemodynamic fluctuation, lower stress index, and protect the brain in patients who undergo craniocerebral surgery under inhalation anesthesia with sevoflurane. The results can provide evidence to support clinical application of dexmedetomidine combined with sevoflurane for craniocerebral surgery. 

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    Application and characteristics of decellularization technology in tissue engineered trachea
    Wang Zhihao, Wu Cong, Wu Sihua, Shi Hongcan
    2020, 24 (35):  5695-5700.  doi: 10.3969/j.issn.2095-4344.2773
    Abstract ( 352 )   PDF (545KB) ( 168 )   Save

    BACKGROUND: Repair of long tracheal injury has always been a major challenge in tracheal therapy. Tissue engineering tracheal decellularization technology can provide an effective treatment approach for long tracheal injury repair.

    OBJECTIVE: To review the advantages and disadvantages of different acellular techniques in tissue engineered trachea and their application in tracheal replacement therapy.

    METHODS: Using the terms “tissue engineered trachea, decellularization, tracheal reconstruction, tracheal replacement therapy” as key words, CNKI, Wanfang and PubMed database from January 2006 to November 2019 were analyzed and summarized.

    RESULTS AND CONCLUSION: Long tracheal injury is mainly caused by tumor, trauma, stenosis, and infection. It requires tracheal replacement for airway reconstruction therapy, and the decellularized tracheal matrix prepared by acellular technology in tissue engineering research is an effective way for its treatment. Decellularization technology removes the immunogenicity of tissues or organs through physical, chemical and biological enzymes, and effectively retains the extracellular matrix of tissues and organs, providing a supportive environment for remodeling functional trachea. After surgery, patients do not need to rely on immunosuppressants. At present, there are cases of decellularization technology used in clinical tracheal transplantation, but patients have more complications after surgery, and its functions need to be further improved. With the development of decellularization technology, acellular methods have become more mature, sophisticated and diversified, providing directions and approaches for future clinical tracheal treatment. 

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    Immunomodulation of extracellular matrix and its role in tissue regeneration
    Yang Wenxiao, Yang Ning, Liu Yao
    2020, 24 (35):  5701-5707.  doi: 10.3969/j.issn.2095-4344.2873
    Abstract ( 488 )   PDF (743KB) ( 175 )   Save

    BACKGROUND: In biological organisms, there is a mutual regulation between the extracellular matrix and immune system. Immune cells are involved in the continuous remodeling of the extracellular matrix. Proteins and cytokines in the extracellular matrix influence the adhesion, migration, proliferation and differentiation of immune cells.

    OBJECTIVE: To review the immunomodulatory effect and mechanism of the extracellular matrix that sends immunomodulatory signals, participates in immune response and is rich in immunoreactive factors.

    METHODS: The authors searched the articles published from 2002-2019 in PubMed and CNKI with the keywords of “extracellular matrix, immune regulation, immune microenvironment; tissue regeneration” in English and Chinese, respectively. Articles irrelevant to the purpose of the present article, and articles of low quality and repeatability were excluded, and 60 articles were finally selected for review.

    RESULTS AND CONCLUSION: The extracellular matrix can not only provide structural support for tissue cells in normal physiological activities, and its rich protein components and immunoreactive molecules also play an indispensable role in immune regulation when the body responds to external stimuli. The extracellular matrix can participate in the immune response in both steady-state and pathological state, provide a suitable microenvironment for tissue regeneration and play a role in tissue repair and regeneration. Allogeneic tissue or organ transplantation is mainly used in the clinical reconstruction of damaged or defected tissues and organs, but usually cannot achieve good results due to shortage of donors and transplant rejection. Tissue engineering technology provides a new direction for the reconstruction of damaged tissues and organs. However, there are still many problems to be further studied, including the mechanism of extracellular matrix in tissue regeneration, optimized application method, standardized preparation and industrialization of extracellular matrix bioscaffolds.

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    Advantages of three-dimensional printing technology in neurosurgery
    Wen Xichao, Zeng Zhaomu, Tang Yushan, Fu Meijuan, Wu Wensong, Zheng Kebin
    2020, 24 (35):  5708-5714.  doi: 10.3969/j.issn.2095-4344.2876
    Abstract ( 392 )   PDF (649KB) ( 115 )   Save

    BACKGROUND: The nervous system has a complex anatomical structure, where various related diseases can occur. The operation on the nerve system is difficult with high risk. Doctors are required to remove the diseased tissue completely, but not to damage important nerves, blood vessels and functional areas during the operation. Therefore, treatment methods and related auxiliary methods with accurate positioning and high surgical precision have been explored clinically. Three-dimensional (3D) printing is a rapid prototyping technology that has developed rapidly in recent years and has been widely used in biomedical industry.

    OBJECTIVE: To review the application status and prospect of 3D printing technology in neurosurgery.

    METHODS: The first author of this paper searched CNKI, WanFang, PubMed and Web of Science databases

    by using key words through computer. The deadline for publications was February 2020. A total of 385 related articles were retrieved. According to the inclusion and exclusion criteria, 49 articles were used for review after literature supplement.  

    RESULTS AND CONCLUSION: In the field of neurosurgery, 3D printing customizes individualized implants that can be used to repair skull defects. The printed lesion model can be used for preoperative simulation of surgeries on deformity repair, cerebrovascular disease, skull base disease and spinal cord disease and provide the basis for individualized precision therapy. The model can also be used for neurosurgical education and preoperative education. Therefore, 3D printing technology has a broad development prospect in the field of neurosurgery.

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    Network meta-analysis of different drugs for the treatment of primary osteoporosis
    Que Minqiang, Shi Chushuo, Huang Yingjie, Zhan Qunzhang, Huo Chenxing, Zhou Chi, Yang Renxuan
    2020, 24 (35):  5715-5722.  doi: 10.3969/j.issn.2095-4344.2879
    Abstract ( 424 )   PDF (638KB) ( 105 )   Save

    BACKGROUND: Clinical studies have found that alendronate combined with other drugs such as calcitonin and calcium can improve the clinical efficacy on primary osteoporosis and reduce the incidence of adverse reactions, but there is no systematic review.

    OBJECTIVE: To systematically evaluate the clinical efficacy, bone density, and safety of different drugs in the treatment of primary osteoporosis.

    METHODS: A computer search of PubMed, China Knowledge Network database, VIP, WanFang database, Embase, CBM and the Cochrane Library was performed for randomized controlled trials of different drugs for the treatment of primary osteoporosis. After literature screen and data extraction, the quality of the included literatures was assessed using the Cochrane System and RevMan 5.3. Bayesian network meta-analysis was performed using Stata 15.0 software and Markov chain-Monte Carlo method.

    RESULTS AND CONCLUSION: A total of 14 randomized controlled trials with 1 822 patients were enrolled, involving alendronate, zoledronic acid, calcium, calcium combined with zoledronic acid, alendronate combined with calcium, alendronate combined with bone peptide injection, calcium combined with bone peptide injection, alendronate combined with teriparatide injection, and salmon calcitonin. The results of the network meta-analysis showed that there were nine interventions in terms of improving the total effective rate, which ranked as follows: calcium combined with bone peptide injection > alendronate combined with bone peptide injection > alendronate combined with zoledronic acid > zoledronic acid > zoledronic acid combined with calcium > salmon calcitonin > alendronate combined with calcium > alendronate > calcium. In terms of improving bone mineral density after treatment, there are five interventions, which ranked as follows: alendronate combined with calcium > calcium > calcium combined with zoledronic acid > zoledronic acid > alendronate. In terms of reducing the incidence of adverse reactions, seven interventions were involved, which ranked as follows: calcium > alendronate combined with calcium > alendronate combined with bone peptide injection > zoledronic acid combined with calcium > zoledronic acid > alendronate > alendronate combined with teriparatide injection. In conclusion, calcium combined with bone peptide injection is the best measure to improve the total effective rate in the treatment of primary osteoporosis. Calcium is effective in improving bone density after treatment, and calcium combined with alendronate has a synergistic effect, with lowest incidence of adverse reactions and best therapeutic effect.

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    Different acupuncture therapies for treating periarthritis of the shoulder: overview of systematic reviews and network Meta-analysis
    Zhang Jinhuan, Yuan Weiqu, Chen Chen, Huang Xingxian, Yu Haibo
    2020, 24 (35):  5723-5732.  doi: 10.3969/j.issn.2095-4344.2352
    Abstract ( 479 )   PDF (701KB) ( 129 )   Save

    BACKGROUND: Increasing systematic reviews of acupuncture treatment for periarthritis of shoulder indicate that acupuncture treatment has better efficacy than western medicine. However, the methodological quality of these systematic reviews and the differences in efficacy between different acupuncture therapies are unclear.

    OBJECTIVE: To evaluate the methodological quality of systematic reviews regarding acupuncture therapy for periarthritis of shoulder and to compare the efficacy of different acupuncture therapies in treating periarthritis of the shoulder.

    METHODS: A total of seven electronic databases were searched for systematic reviews regarding different acupuncture therapies for periarthritis of the shoulder, from inception to December 28, 2019. The AMSTAR2 instrument was used to evaluate the methodological quality of included systematic reviews. The eligible randomized controlled trial (RCTs) were selected from the included systematic reviews and updated RCTs from the above systematic reviews to December 28, 2019. Cochrane risk of bias tool was used for the risk of bias of the included RCTs. Pairwise meta-analyses were performed using the random-effects model, and network meta-analysis of the included RCTs were performed the frequentist framework. All data analyses were completed in Stata 14.0.

    RESULTS AND CONCLUSION: Thirty-four qualified RCTs (n=3 098) were included from five critically low-quality systematic reviews and updated RCTs. Five interventions were ranked based on the ranking probability in the network meta-analysis. Compared with western medicine, warm acupuncture [odds ratio (OR)=1.26, 95% confidence interval (CI) (1.15, 1.39)] has the highest possibility to improve the symptoms of periarthritis of the shoulder, followed by thermo-sensitive moxibustion [OR=1.26, 95%CI (1.15, 1.39)], electroacupuncture [OR=1.21, 95%CI (1.10, 1.33)], filiform needle [OR=1.21, 95%CI (1.01, 1.24)]. In terms of visual analogue scale score, compared with western medicine, thermo-sensitive moxibustion [OR=0.12, 95%CI (0.03, 0.46)] had the highest possibility of reducing visual analogue scale score followed by warm acupuncture [OR=0.28, 95%CI (0.11, 0.75)] and electroacupuncture [OR=0.34, 95%CI (0.12, 0.96)]. Considering the pairwise meta-analyses and network meta-analysis of this study, among the four acupuncture therapies included, thermo-sensitive moxibustion and warm acupuncture can be considered as a complementary alternative to the treatment of periarthritis of the shoulder. However, given the critically low methodological quality of the included systematic reviews and poor reporting risk bias of RCTs, more rigorous design and standardized reporting are needed to further demonstrate the reliability of this study.

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    A meta-analysis of kinesio taping in the treatment of delayed onset muscle soreness
    Geng Zhizhong, Pei Ziwen, Yan Gongli, Chen Jian
    2020, 24 (35):  5733-5740.  doi: 10.3969/j.issn.2095-4344.2351
    Abstract ( 404 )   PDF (589KB) ( 132 )   Save

    BACKGROUND: Previous studies have shown the inconsistent efficacy of kinesio taping on delayed onset muscle soreness.

    OBJECTIVE: To quantitatively evaluate the effect of kinesio taping on delayed onset muscle soreness by means of Meta-analysis, in order to provide theoretical basis for the clinical application of this technique.

    METHODS: Randomized controlled trials of kinesio taping for treatment of delayed onset muscle soreness was retrieved from CNKI, WanFang, Web of Science, PubMed, EBSCO and other databases. The retrieval time was from inception to October 2019. The risk assessment criteria for RCT bias in the Cochrane collaboration were used for methodological quality assessment, and the RevMan 5.3 software was used for Meta-analysis. Meta-regression analysis was performed using Stata 15.0.

    RESULTS AND CONCLUSION: Nine RCTs were finally included, with a total of 382 patients. Meta-analysis results showed that the subjective pain score (visual analogue scale) in the kinesio taping group was significantly lower than that in the non-stimulation group [standard mean difference (SMD)=-0.85, 95% confidence interval (CI) (-1.32, -0.39), P=0.000 3], and the creatine kinase level in the kinesio taping group was not significantly different from that in the non-stimulation group [SMD=0.30, 95%CI (-0.17, 0.76), P=0.21]. Compared with the false stimulation group, the kinesio taping group showed no significant difference in the subjective pain score [SMD=-0.20, 95%CI (-0.46, 0.06), P=0.13)] and creatine kinase level [SMD=0.22, 95%CI (-0.06, 0.49), P=0.12]. It suggests that kinesio taping may be beneficial to reduce subjective pain in patients with delayed onset muscle soreness, and there is a placebo effect.

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