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    18 January 2022, Volume 26 Issue 2 Previous Issue    Next Issue
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    Effects and mechanism of the combined use of L-carnitine, pantothenic acid and coenzyme Q10 on aerobic exercise-induced fatigue in mice
    Jia Ruizhen, Jiang Chao, Jin Qiguan, Lou Xujia, Hu Yulong
    2022, 26 (2):  165-170.  doi: 10.12307/2022.028
    Abstract ( 582 )   PDF (703KB) ( 62 )   Save
    BACKGROUND: Previous studies have confirmed that L-carnitine, pantothenic acid, coenzyme Q10 and other nutritional factors can improve the body’s energy metabolism, which are essential components in the energy conversion process. Whether a combination of these three nutritional factors produces better protection against exercise fatigue is not yet clear.
    OBJECTIVE: To explore whether the combined use of L-carnitine, pantothenic acid, and coenzyme Q10 can improve exercise-induced fatigue in mice, the best combination and the mechanism of improvement in exercise-induced fatigue.
    METHODS: (1) Animal grouping: Using the principle of orthogonal design, 90 male ICR mice were divided into 10 groups according to different nutritional factors (L-carnitine (A), pantothenic acid (B), and coenzyme Q10 (C)), different dosages (dose 1: no use; dose 2: therapeutic dose; dose 3: three times the therapeutic dose), and whether to swim training or not (D). Another 10 mice were enrolled in exercise control group. (2) Establishment of an aerobic exercise-induced fatigue model: All the mice swam for 1 hour with 5% weight per day, 6 days a week, for 6 weeks. At the end of the 5th week, the mice in the former nine groups were performed with an exhaustion swimming and the exhaustion time was recorded. Nutritional factors were administered by oral gavage 1 hour before exercise. (3) Detection index: There were three experimental groups: normal control group, exercise control group, and exercise+pantothenic acid+Q10 group (exercise+nutritional factor group with the longest duration of exhaustion). At 24 hours after the end of 6-week exercise, the levels of blood urea nitrogen, superoxide dismutase, and malondialdehyde in serum and muscle tissue were detected. This experimental protocol was approved by the Animal Ethics Committee of Yangzhou University on September 15, 2019.
    RESULTS AND CONCLUSION: (1) Effects on weight-bearing swimming exhaustion time were ranked as follows: exercise > pantothenic acid > coenzyme Q10 > L-carnitine. The group with the longest exhaustion time was A1B3C3D2 combination (exercise+nutritional factor group). (2) The blood urea nitrogen level of the exercise control group was significantly higher than the normal control group (P < 0.05). The blood urea nitrogen level of exercise+nutritional factor group was significantly lower than that of the exercise control group (P < 0.01). (3) The superoxide dismutase levels in serum and muscle tissue of the exercise control group were significantly lower than those of the normal control group (both P < 0.01). The superoxide dismutase levels in serum and muscle tissue of the exercise+nutritional factor group  were significantly higher than those of the exercise control group (both P < 0.05). (4) The malondialdehyde levels in serum and muscle tissue of the exercise control group were significantly higher than those of the normal control group (both P < 0.05). The malondialdehyde levels in serum and muscle tissue of the exercise+nutritional factor group were significantly lower than those of the exercise control group (both P < 0.05). To conclude, exercise combined with pantothenic acid+nutritional factors strengthens the body's antioxidant capacity and reduces oxidative stress levels, thereby prolonging exercise time and delaying the occurrence of exercise-induced fatigue.
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    Identification and expression of exogenous target genes in transgenic tomato
    Guan Weiwei, Gu Yu, Guan Xiaoyan, Wu Jiayuan, Bai Guohui, Tian Yuan, Liu Jianguo
    2022, 26 (2):  171-175.  doi: 10.12307/2022.029
    Abstract ( 463 )   PDF (750KB) ( 158 )   Save
    BACKGROUND: Edible vaccines from transgenic plants is to integrate exogenous genes into the plant genome with plants as carriers, further activating animal or human immune system to obtain specific immunity. However, the continuous low expression of exogenous genes has been unable to achieve satisfactory immune effects.
    OBJECTIVE: To detect the foreign fused gene pacA-ctxB gene and interest protein expression level in the transgenic tomato by molecular biological technique, providing a research basis for further observation of the anti-caries effect of edible caries vaccines. 
    METHODS: After extracting the total DNA of transgenic tomato leaves, the exogenous fused gene pacA-ctxB was detected by PCR. There were three groups in the experiment: a positive control group (plasmid p2355-EPC10), a blank control group (an ordinary tomato plant, Hongkang 219), and a transgenic group (nine transgenic tomato plants). Total proteins were extracted and quantitatively tested with BCA kit and expression of PAcA/CTB in the transgenic tomato was analyzed by western blot and ELISA. There were two groups for detection of target proteins: a transgenic group (five transgenic tomato plants expressing exogenous chimeric genes (positive PCR test) and a blank control group (one ordinary tomato plant).
    RESULTS AND CONCLUSION: PCR amplification results showed that there were 5 of the 9 strains of transgenic tomatoes in which the specific amplification bands were about 1.7 kb, accounting for 55% of the total detected transgenic plants. The total protein in the transgenic tomato was 3.15 g/L. Western blot results showed high density bands at 5.8 kD for PCR-positive transgenic tomato protein samples, and no specific bands were found in non-transgenic tomato protein samples. ELISA results showed that the expression of target proteins was about 4.12 mg/L, accounting for 0.13% of the total soluble protein in the transgenic tomato. To conclude, the exogenous fusion gene pacA-ctxB can be expressed in tomato plants and produce target proteins.
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    Establishing a murine model of experimental apical periodontitis induced by Fusobacterium nucleatum
    Wang Jiajia, Liu Jie, Wang Min
    2022, 26 (2):  176-181.  doi: 10.12307/2022.030
    Abstract ( 449 )   PDF (1086KB) ( 85 )   Save
    BACKGROUND: Apical periodontitis is a common oral inflammatory disease. Research on animal models for this disease has been extensively carried out, but there is yet no unified method for establishing such models.
    OBJECTIVE: To establish a murine model of experimental apical periodontitis model induced by Fusobacterium nucleatum.
    METHODS: Twenty-five BALB/c mice were divided into normal control group (n=5) and experimental group (n=20). Mice in the normal control group were sacrificed at 0 day to collect the lower jaws. In the experimental group, the root canal of the lower first molar was exposed followed by injection of Fusobacterium nucleatum suspension, and then the tooth crown was sealed with temporary restorative material. In the experimental group, five mice were selected at each observational time points (1, 3, 5, 7 days postoperatively), and samples of the mandible were collected accordingly. Micro-CT was performed to analyze alveolar bone resorption. The periapical tissue changes were observed by hematoxylin-eosin staining. Tartrate resistant acid phosphatase staining was applied to detect the expression of osteoclasts. 
    RESULTS AND CONCLUSION: Micro-CT scan showed that the apical periodontal space of the lower first molars began to widen at 3 days postoperatively and significant alveolar bone resorption was developed at 7 days. Three-dimensional reconstruction of the apical region showed decreased bone volume fraction and increased trabecular separation in the apical region at 7 days postoperatively (P < 0.05). Hematoxylin-eosin staining showed that inflammatory cell infiltration was obviously visible in the apical region at 3 days postoperatively, and then the infiltration gradually expanded. Tartrate resistant acid phosphatase staining showed a sustained increase in the number of osteoclasts in the apical region at 3, 5, and 7 days postoperatively. To conclude, the murine model of experimental apical periodontitis can be successfully established by inoculating Fusobacterium nucleatum into the root canals, based on which, we can further explore the etiology, pathology and treatment of apical periodontitis.
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    PDZ domain containing 1 deficiency promotes chondrocyte senescence in osteoarthritis
    Guan Hong, Zhang Hongbo, Shao Yan, Guo Dong, Zhang Haiyan, Cai Daozhang
    2022, 26 (2):  182-189.  doi: 10.12307/2022.031
    Abstract ( 508 )   PDF (954KB) ( 72 )   Save
    BACKGROUND: Osteoarthritis is characterized by the degeneration of articular cartilage. Senescence of chondrocytes, the only type of cells in cartilage, is one of the most important mechanisms of osteoarthritis. However, the specific pathogenesis of osteoarthritis is still unclear. Therefore, we explored the molecular mechanism and signal pathway changes in the disease process and expected to provide new biological targets and research directions for the diagnosis and treatment of osteoarthritis.
    OBJECTIVE: To investigate the effect of PDZ domain containing 1 (PDZK1) on chondrocyte senescence in osteoarthritis.
    METHODS: (1) Eight-week-old C57 mice were randomly divided into experimental group and sham operation group. Experimental group was then randomly divided into two subgroups of 4 weeks and 8 weeks. In the experimental group, the tibia ligament of the right knee was cut off to dissociate the medial meniscus to induce osteoarthritis. In the sham operation group, only the joint capsule was cut without medial ligament resection and meniscus dissociation. The expression of PDZK1 was detected. (2) The chondrocytes from neonatal mice were isolated by collagenase type II digestion, and cultured. Subsequently, 10 μg/L interleukin-1β was used to stimulate the chondrocytes in order to establish an in vitro cell model of osteoarthritis, and the expression of PDZK1 was knocked down by siRNA-PDZK1. The cells were then divided into untreated group, interleukin 1β treatment group (IL-1β), siRNA-PDZK1 group (si-PD), interleukin 1β and siRNA-PDZK1 co-stimulation group (si-PD+IL-1β). Firstly, we detected the expression of PDZK1 in the chondrocytes. Moreover, chondrocyte formation indicators, such as type II collagen a1, the catabolism indicators, such as matrix metalloproteinase 13, and chondrocyte senescence indicators, including P16, P21, P53, were tested.
    RESULTS AND CONCLUSION: Compared with the sham operation group, the expression of PDZK1 was decreased. In the primary chondrocytes of C57/BL6 suckling mice, it was confirmed by western blot that the expression of PDZK1 was decreased significantly in the IL-1β group and si-PD group compared with the untreated group. Furthermore, the expression of type II collagen a1 was reduced markedly in the si-PD group compared with the untreated group. Additionally, the expression of matrix metalloproteinase 13 in si-PD+IL-1β group was increased dramatically compared with the IL-1β group. In the primary chondrocytes of C57/BL6 suckling mice, it was confirmed by real-time fluorescent quantitative PCR that after knocking down the expression of PDZK1 in the si-PD group, the expression of cell senescence indicators, including P16, P21, and P53, were increased significantly compared with the untreated group. These findings indicate that the expression of PDZK1 in chondrocytes is decreased during osteoarthritis progression. PDZK1 deficiency promotes chondrocyte senescence, and exacerbates osteoarthritis. Therefore, PDZK1 may be an important gene that regulates cellular senescence in chondrocytes during the pathogenesis of osteoarthritis, and relevant mechanisms need further studies. 
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    A single bout of exhaustive exercise induces renal NOD-like receptor protein 3 inflammasome expression in rats
    Geng Yuanwen, Lin Qinqin, Li Ruoming, Tang Shaokai, Wang Baihui, Tian Zhenjun
    2022, 26 (2):  190-196.  doi: 10.12307/2022.032
    Abstract ( 422 )   PDF (910KB) ( 43 )   Save
    BACKGROUND: Exhaustive exercise leads to multiple redistribution of blood oxygen in the body, induces a strong inflammatory response, enhances the level of systemic inflammation, and damages kidney function.
    OBJECTIVE: To determine the effects of a single bout of exhaustive exercise on the expressions of renal NOD-like receptor protein 3 (NLRP3) inflammasome in rats and possible mechanism.
    METHODS: Twenty male Sprague-Dawley rats aged 3 months were randomly divided into a control group and an exhaustive exercise group, with 10 rats in each group. In the exhaustive exercise, three-level incremental exercise load treadmill training was performed to establish a one-time exhaustive exercise experimental animal model. No modeling was performed in the control group. Immediately after training, blood sample was collected from each rat, and then the kidney tissue was removed for hematoxylin-eosin staining to observe the morphological changes of renal cells. Renal thioredoxin-interacting protein (TXNIP), serum blood urea nitrogen, creatinine, creatine kinase, malondialdehyde, cystatin C and urine kidney injury molecule-1 levels were detected. Western blot was used to detect renal SIRT1, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) 1, Caspase-1 and interleukin-1β protein expression. RT-qPCR was performed to detect serum and renal miR-155 and renal SIRT1 mRNA expression. Meanwhile, renal cell morphology was observed.
    RESULTS AND CONCLUSION: Compared with the control group, the levels of serum and renal miR-155 were significantly increased in the exhaustive exercise group (P < 0.01, P < 0.05). Compared with the control group, the protein and mRNA expression of renal SIRT1 was significantly decreased (both P < 0.01), while the protein expression of renal TXNIP, NLRP3, ASC-1, Caspase-1 and interleukin-1β was significantly increased in the exhaustive exercise group (P < 0.05 or 0.01). Moreover, the levels of serum blood urea nitrogen, creatinine, creatine kinase, malondialdehyde, cystatin C and urine kidney injury molecule-1 were significantly increased in the exhaustive exercise group compared with the control group (P < 0.05 or 0.01), and renal pathologic changes were aggravated. The expression of SIRT1 was negatively related to the protein expression of TXNIP and NLRP3 (r=-0.962, P < 0.01; r=-0.977, P < 0.01). The expression of miR-155 was negatively related to the protein expression of SIRT1 (r=-0.989, P < 0.01), and positively related to the protein expression of TXNIP and NLRP3 (r=0.902, P < 0.01; r=0.968, P < 0.05). Therefore, a single bout of exhaustive exercise increases the levels of serum and renal miR-155, reduces the expression of renal SIRT1 protein and mRNA, increases the expression of renal TXNIP, activates NLRP3 inflammasome, triggers inflammatory response and then aggravates the renal pathological damages, thereby impairing renal function. This may be one of the mechanisms of kidney injury induced by a single bout of exhaustive exercise.
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    Pharmacological mechanism of Shenling Baizhu San in the treatment of knee osteoarthritis based on network pharmacology and molecular docking
    Li Anan, Jiang Tao, Zhan Min, Cai Yuning, Song Min, Li Congcong, Lin Wenzheng, Zhang Jiayuan, Liu Wengang
    2022, 26 (2):  197-204.  doi: 10.12307/2022.033
    Abstract ( 668 )   PDF (1747KB) ( 76 )   Save
    BACKGROUND: Shenling Baizhu San is one of the representative prescriptions for strengthening the spleen and removing dampness, which has good anti-inflammatory and immunomodulatory effects. In recent years, we have found positive effect of Shenling Baizhu San in patients with early and mid-stage knee osteoarthritis in clinical practice, but the specific molecular mechanism is still unclear.
    OBJECTIVE: To explore the pharmacological mechanism of Shenling Baizhu San in the treatment of knee osteoarthritis through network pharmacology and molecular docking. 
    METHODS: The TCMSP and TCMID databases were used to collect the active ingredients and their targets of Shenling Baizhu San. The GenneCards and OMIN-NCBI databases were used to obtain the KOA targets. STRING and Cytoscape were used to construct the drug-active chemical ingredient-core target network and the protein-protein interaction (PPI) analysis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. AutoDockTools was used to predict molecular docking between important active ingredients and core targets. 
    RESULTS AND CONCLUSION: A total of 109 active pharmaceutical chemical components of Shenling Baizhu San were screened, and the important components included luteolin, kaempferol, β-sitosterol, etc. Among them, there were 97 intersecting targets with diseases, and the core targets were PTGS2, CASP3, AKT1, MAPK1, MAPK8, TP53, EGFR, etc. The results of molecular docking showed that kaempferol and β-sitosterol could target and regulate CASP3, AKT1, and PTGS2. GO analysis showed that the mechanism mainly involved biological processes such as oxidative stress, lipopolysaccharide, nutritional level, muscle cell proliferation, oxygen level, etc. The results of KEGG analysis showed that PI3K-Akt, tumor necrosis factor, interleukin-17 and Th17 cell pathways were the main signaling pathways. In summary, Luteolin, kaempferol, β-sitosterol, and other active ingredients in Shenling Baizhu San can treat knee osteoarthritis by inhibiting inflammation, regulating apoptosis, and reducing oxidative stress. 
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    Ligustrazine furoxan complex protects against renal ischemia-reperfusion injury in mice
    Li Wanhai, Dong Yuhang, Shi Chao, Jiang Yiyao, Liu Ge, Diao Wenjie, Wu Zhen
    2022, 26 (2):  205-210.  doi: 10.12307/2022.034
    Abstract ( 420 )   PDF (1177KB) ( 78 )   Save
    BACKGROUND: Ligustrazine and nitric oxide can both reduce acute kidney injury caused by renal ischemia-reperfusion. Our team synthesized a compound of ligustrazine furoxan (605-1) which can be degraded into ligustrazine monomer and nitric oxide in animals. This compound has therapeutic and preventive effects against ischemia-reperfusion injury.
    OBJECTIVE: To observe the therapeutic and preventive effects of 605-1 against acute renal ischemia-reperfusion injury in mice, and to explore its mechanism.
    METHODS: Forty-eight male C57 mice were randomly divided into six groups: sham operation group, model group (ischemia-reperfusion group), single administration group (605-1, 30 mg/kg), low, medium and high dose groups (ischemia-reperfusion+10, 20, 30 mg/kg 605-1, respectively). Mice in the sham operation group and the single administration group underwent sham operation without renal ischemia treatment, and those in the model group and the three administration groups were used to make acute kidney injury models caused by renal ischemia-reperfusion. Pre-treatments in each group were conducted at 24 and 2 hours before operation. Normal saline was intraperitoneally given in the sham operation and model groups. After 24 hours of ischemia-reperfusion, the levels of serum creatinine and urea nitrogen and the pathological changes of renal tissue were measured. The expression of kidney injury molecule 1, Nox4, p65, and P-p65 was detected at the protein level. The expression of kidney injury molecule 1, tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 were detected at the RNA level. All animal experiment procedures were approved by the Animal Ethics Committee of Anhui Medical University.
    RESULTS AND CONCLUSION: The single administration group (30 mg/kg) had no renal toxicity. Compared with the model group, in the low, medium and high dose groups, histomathological examinations of the renal tissue showed pathological renal tubule dilation and brush border loss, tubular cell loss was significantly reduced, serum creatinine and urea nitrogen levels were significantly reduced; the protein and mRNA levels of kidney injury molecule 1 in renal tissue also decreased significantly, and immunohistochemical examination showed that the distribution and quantity of kidney injury molecule 1 expression in renal tissue decreased significantly; the protein levels of Nox4, p65, and P-p65 were down-regulated; the mRNA levels of tumor necrosis factor-α, interleukin-6 and monocyte chemoattractant protein 1 were significantly reduced. To conclude, 605-1 has a preventive effect against renal ischemia-reperfusion injury in mice, and its mechanism is related to anti-oxidative stress and inhibition of inflammation.
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    Asperosaponin VI therapy for Achilles tendinopathy in rabbits
    Wang Kun, He Benxiang
    2022, 26 (2):  211-217.  doi: 10.12307/2022.035
    Abstract ( 465 )   PDF (1200KB) ( 40 )   Save
    BACKGROUND: In recent years, tendonopathy occurs frequently as a chronic orthopedic injury, and there is still a lack of effective treatment as yet. Dipsacus L. has the effect of tonifying the liver and kidney, strengthening bones, and sustaining broken injuries.
    OBJECTIVE: To analyze the repairing effect of Asperosaponin VI in a rabbit model of Achilles tendinopathy.
    METHODS: Forty-eight rabbits were randomized into a normal control group (n=8), a model group (n=32), and a noral saline group (n=8). In the model group, the model of tendinopathy was made at the left calcaneus attachment injected with prostaglandin E2, and the models were then randomized into four subgroups, which were treated with 0, 10, 20, and 40 mg/kg Asperosaponin VI, respectively. Treatments in each group were conducted once a day for 4 consecutive weeks. The study protocol was approved by the Animal Ethics Committee of Chengdu Sport University with an approval No. [2020]21 on November 4, 2019. 
    RESULTS AND CONCLUSION: Compared with the normal control group, the expression of matrix metalloproteinase-1 was significantly higher in the model group (P < 0.05). Compared with the model group, the expression of matrix metalloproteinase-1 was significantly reduced in the 20 and 40 mg/kg groups (P < 0.05). The expression of tissue inhibitor of matrix metalloproteinases 1 was significantly higher in the model group than the normal control group (P < 0.05), while the expression of tissue inhibitor of matrix metalloproteinases 1 was significantly reduced in the 10, 20 and 40 mg/kg groups compared with the model group (P < 0.05). The expression of transforming growth factor-β1 was significantly higher in the 10, 20 and 40 mg/kg groups compared with the model group (P < 0.05). The expression of plasminogen activator inhibitor 1 was significantly higher in the 40 mg/kg group than the model group (P < 0.05). Tendon fibers in the 40 mg/kg group were intact and arranged orderly, which were similar to normal tendon tissue. Therefore, Asperosaponin VI can inhibit vicious cycle of degeneration of collagen in the extracellular matrix, induce the proliferation of tenocytes and promote the healing. It may be a potential drug for the treatment of tendinopathy.
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    Pathological changes in rats with ischemic stroke induced by improved photochemical embolization
    Li Shulun, Hao Peng, Hao Fei, Duan Hongmei, Zhao Wen, Gao Yudan, Yang Chaoyang, Li Xiaoguang
    2022, 26 (2):  218-224.  doi: 10.12307/2022.036
    Abstract ( 862 )   PDF (1588KB) ( 54 )   Save
    BACKGROUND: A rat model of photochemical embolization can simulate ischemic stroke well, with the advantages of specific damage to the brain area, high reproducibility and low mortality. However, the choice of light source and the concentration of rose bengal injection have certain effects on the model. So, a detailed evaluation is needed to determine whether the animal model is established successfully.
    OBJECTIVE: To establish a stable model of ischemic stroke in rats that is less liable to recover spontaneously, and to explore the pathological changes in the infarct region and behavior changes in rats.
    METHODS: A total of 52 male Wistar rats were randomly divided into sham operation group (n=6) and photochemical embolization group (n=46). In the photochemical embolization group, 20, 40, and 80 mg/kg rose bengal was injected into the rat femoral vein to make photochemical embolization models, and meanwhile the optimal rose bengal concentration was screened out. The remaining 28 rats were subjected to photochemical embolization. Rats in the sham operation group were not irradiated with laser and were not injected with rose bengal dye. TTC staining was used to reveal the changes in infarct size at 1 day after injection with different concentrations of rose bengal. NeuN staining was used to observe neuronal death in the infarct region at 1, 3, 7, and 14 days after photochemical embolization. Iba-1, GFAP, and GLUT-1 staining were employed to observe the changes of inflammatory responses, glial scars and blood vessels in the infarct region after photochemical embolization. Cylinder experiment and grid error experiment were used to evaluate the behavioral changes of rats after photochemical embolization.
    RESULTS AND CONCLUSION: Injection with 80 mg/kg rose bengal caused the largest size of stroke cavity, resulting in a high reproducibility and a low animal mortality. A stable stroke cavity could be formed within 7 days after injection. Relatively stable glial scar zone formed at 7 days after photochemical embolization, but inflammatory reactions gradually aggravated in 1-14 days. Photochemical embolization reduced the area of blood vessels near the stroke cavity, and the area tended to be stable at 14 days. The rats experienced long-term decline in sensation and motor function after photochemical embolization. To conclude, the rat model of photochemical embolization is stable and not easy to recover spontaneously, which is suitable for studying the pathological changes after ischemic stroke.
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    Electroacupuncture intervenes with changes of mitogen-activated protein kinase pathway in a rat model of cerebral ischemia/reperfusion due to middle cerebral artery occlusion
    Lai Han, Wang Jiao, Dong Miaomiao, Luo Meng, Wang Wenhao, Zhou Guoping
    2022, 26 (2):  225-231.  doi: 10.12307/2022.037
    Abstract ( 532 )   PDF (986KB) ( 81 )   Save
    BACKGROUND: The mechanisms underlying the protection of electroacupuncture against cerebral ischemia/reperfusion injury in rats and its temporal efficacy have been less studied in the past.
    OBJECTIVE: To observe the effect of electroacupuncture on the expression of p-ERK, p-JNK and p-p38MAPK proteins in three signaling pathways of the MAPK family in rats with cerebral ischemia/reperfusion at different times, and to explore the specific mechanism underlying the cerebral protection of electroacupuncture.
    METHODS: 150 Sprague-Dawley male rats were randomly divided into sham-operated group, model group, and electroacupuncture group, with 50 rats in each group. Each group was then set up for ischemia 1.5 hours followed by reperfusion for 2 hours, 6 hours, 1 day, 3 days, and 7 days, with 10 rats in each subgroup. Single electroacupuncture treatment at Hegu, Shakuze, Zusanli, and Sanyinjiao was conducted at the given time, giving sparse waves at a frequency of 2 Hz, intensity of 1 mA, 20 minutes for one session. Rats in the model and sham-operated groups were grasped simultaneously for fixation at the same time of electroacupuncture, but no electroacupuncture intervention was performed. After anesthesia, the brains were decapitated at the corresponding time points, and neurological deficit scoring was used to observe the infarct area by TTC staining. The expression of p-ERK, p-JNK, and p-p38MAPK was detected by double immunofluorescence labeling method.
    RESULTS AND CONCLUSION: Compared with the sham-operated group, the model group had higher neurological deficit scores and larger infarct size in each subgroup in the same period (P < 0.05). Compared with the model group, there were significantly lower neurobehavioral scores and smaller infarct size in the electroacupuncture subgroups of 6 hours, 1 day and 3 days (P < 0.05). Compared with the model group, the electroacupuncture group had significant up-regulation of p-ERK expression at 1 and 3 days of reperfusion (P < 0.05), downregulation of p-JNK expression at 1 and 3 days of reperfusion (P < 0.05), and significant downregulation of p-p38MAPK expression at 6 hours and 3 days of reperfusion (P < 0.05). To conclude, electroacupuncture can reduce infarct size, alleviate neurological deficits, up-regulate p-ERK expression and down-regulate the expression of p-JNK and p-p38MAPK at the same time. The best effect of electroacupuncture is within 6 hours-3 days. Electroacupuncture promotes the repair of brain tissue damage caused by cerebral ischemia/reperfusion and exerts cerebral protection through the regulation of MAPK family signaling pathway.

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    Fasudil inhibits neuronal apoptosis via regulating mitochondrial dynamics in APP/PS1 mice
    Wei Wenyue, Wang Yuyin, Guo Minfang, Zhang Jing, Gu Qingfang, Song Lijuan, Chai Zhi, Yu Jiezhong, Ma Cungen
    2022, 26 (2):  232-238.  doi: 10.12307/2022.038
    Abstract ( 418 )   PDF (1311KB) ( 178 )   Save
    BACKGROUND: The pathogenesis of Alzheimer’s disease is closely related to abnormal mitochondrial dynamics. Our previous research demonstrated that Fasudil has neuroprotective effect. However, it is needed to explore whether Fasudil has beneficial effect on regulating mitochondiral dynamics. 
    OBJECTIVE: To investigate the effect and mechanism of ROCK inhibitor on cognitive function and neuronal apoptosis in Alzheimer’s disease mice. 
    METHODS: Amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice were randomly divided into the Fasudil group (25 mg/kg/d) and normal saline group (equivalent volume normal saline), and wild-type C57BL/6 mice at the same age and gender served as normal controls (same volume normal saline). Administration in each group was given via intraperitoneal injection once daily for 2 months. Spatial cognition of mice was detected by Morris water maze test and Y maze test. Nissl staining was used to observe and analyze the number and morphology of neurons. TUNEL staining was applied to observe neuronal apoptosis. The protein levels of NeuN, Bax, Bcl-2, Cleaved Caspase-3, dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), optic atrophic protein 1 (OPA1), mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2) in hippocampus tissue were determined by western blot test. The expression of NeuN and DRP1 was detected by immunofluorescence staining.
    RESULTS AND CONCLUSION: Fasudil ameliorated cognitive impairment and improved loss of learning, memory and exploration function in APP/PS1 mice.  Compared with the normal control group, the number of survived neurons was decreased, the apoptotic rate of neurons was increased, the expression of Bax and Cleaved Caspase-3 was increased, but the expression of NeuN and Bcl-2 was decreased in APP/PS1 mice. These changes were all strongly reversed by a 2-month treatment of Fasudil. Fasudil markedly down-regulated the expression of DRP1 and FIS1, but remarkably up-regulated the expression of OPA1, Mfn1, and Mfn2. These findings indicate that Fasudil significantly improves the spatial cognitive function in APP/PS1 mice, which may be related to restoring the mitochondrial fission and fusion imbalance so as to inhibit neuronal apoptosis.

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    Molecular network of miR-106b-5p regulating osteoporotic fracture in the elderly
    Wang Hailong, Li Long, Yilihamu Tuoheti, Liu Xu, Nacikedaoerji, Chen Hongtao, Cui Yong
    2022, 26 (2):  239-244.  doi: 10.12307/2022.039
    Abstract ( 408 )   PDF (1130KB) ( 92 )   Save
    BACKGROUND: Osteoporotic fractures are age-related diseases, with increasing incidence and prevalence due to the aging population. 
    OBJECTIVE: To identify whether miRNA is associated with osteoporotic fracture. 
    METHODS: The differential expression of miRNA (DEM) related to osteoporotic fracture in GSE93883 was analyzed by limma package. The target genes of differentially expressed miRNA were predicted by RAID database, and the key miRNAs and target genes were identified by protein-protein interaction network. Enrichment analysis identified the biological functions and signaling pathways involved in target genes. Finally, qPCR and western blot were used to verify the key miRNAs and signal pathways in bone tissue of five elderly patients with osteoporotic fractures and five elderly patients with non-osteoporotic fractures. 
    RESULTS AND CONCLUSION: A total of 21 differentially expressed miRNAs related to osteoporotic fracture were obtained and 530 target genes were predicted. MiR-106b-5p was identified as a key regulatory gene by protein-protein interaction network. The target genes were mainly related to the activation of MAPK activity, PI3K-Akt signaling pathway and transforming growth factor β signaling pathway. In addition, qPCR results confirmed significant downregulation of miR-106b-5p in elderly osteoporotic fracture (P < 0.05). Western blot results showed that PI3K-Akt and transforming growth factor β signaling pathways were significantly activated in elderly osteoporotic fractures. Therefore, miRNA is involved in elderly osteoporotic fracture and is associated with PI3K-Akt and transforming growth factor βsignaling pathways. MiR-106b-5p may inhibit the occurrence of osteoporotic fractures and become a potential marker and therapeutic target.
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    Potential molecular mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on network pharmacology and molecular docking
    Zhang Xiaoyun, Li Huanan, Chen Feng, Chai Yuan, Gan Bin, Li Song, Chen Dingpeng
    2022, 26 (2):  245-252.  doi: 10.12307/2022.040
    Abstract ( 517 )   PDF (1669KB) ( 188 )   Save
    BACKGROUND: Clinical studies have shown that Guizhi Shaoyao Zhimu Decoction is effective in treating gouty arthritis, but its pharmacological mechanism is not yet clear.
    OBJECTIVE: To explore the potential molecular mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on network pharmacology and molecular docking.
    METHODS: The active components and corresponding targets of Guizhi Shaoyao Zhimu Decoction was screened by TCMSP database. The related targets of gouty arthritis were obtained by the query results of Gene Cards, OMIM and DigSee databases. The potential targets of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis were obtained by mapping intersection by Venny platform. The network of “single drug-active target-potential target” and the protein interaction network of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis were constructed by Cytoscape software. The action targets of Guizhi Shaoyao Zhimu Decoction were analyzed by David database including the gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, molecular docking between key active ingredients and key targets was performed using Autodock software. 
    RESULTS AND CONCLUSION: There were 180 active components and 24 targets related to the treatment of gouty arthritis by Guizhi Shaoyao Zhimu Decoction. The key active components were quercetin, formononetin, luteolin, 3'-methoxyglabridin, taxifolin. The key targets were P53, neurotrophic receptor tyrosine kinase 1, Cullin3, estrogen receptor 1, and ubiquitin C. Molecular docking results showed that the key active components showed good binding activity with the key targets of gouty arthritis treatment. GO analysis showed that the key targets were mainly involved in many biological processes such as lipopolysaccharide reaction, bacterial derived molecules response, cell response to biological stimulation, oxidative stress response, regulation of inflammatory response, and response to reactive oxygen species. KEGG pathway analysis showed that Guizhi Shaoyao Zhimu Decoction mainly acted on interleukin-17 pathway, tumor necrosis factor pathway, AGE-RAGE pathway, NOD like receptor pathway, nuclear factor-κB pathway, and Toll like receptor pathway. To conclude, Guizhi Shaoyao Zhimu Decoction could reduce immune-inflammatory reaction, inhibit chondrocyte apoptosis and improve the ability of anti-oxidation stress response by multi-component, multi-target and multi-pathway, so as to play a role in the treatment of gouty arthritis. The protein scaffold drug delivery system can be used orally or locally in the future by screening of effective components, which is conducive to the remission of the disease.
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    Selection of key genes related to biological functions and regulation pathway in periodontal reconstruction
    Feng Dongfei, He Hongxu, Xie Qi, Zhang Lili, Zhou Hui, Li Wei
    2022, 26 (2):  253-259.  doi: 10.12307/2022.041
    Abstract ( 481 )   PDF (937KB) ( 76 )   Save
    BACKGROUND: In periodontal reconstruction tissue engineering, there is a wide range of options for biological signals which cannot be verified in sequence. Using bioinformatics methods, the relevant genes are integrated and analyzed, and the cascade regulatory pathways related to periodontal reconstruction are constructed, to find the key to open periodontal reconstruction.
    OBJECTIVE: To focus on periodontal reconstruction process and regulatory mechanism, aiming at screening out the key initiating genes in periodontal reconstruction and identify ideal gene targets for periodontal therapy.
    METHODS: GO function annotation system was used to analyze the genes of three biological functions including differentiation, osteogenesis, and fibrogenesis involved in periodontal reconstruction, and identify the intersection genes of each function. Integrated data from the major information databases of TRANSFAC, TarBase, TransmiR, miRTarBase and miRecords were collected to establish a "cascade regulatory pathway related to periodontal reconstruction," mapping all the genes in the biological process of periodontal reconstruction onto the regulatory network, to find out all the linear pathways in this subnet by breadth-first algorithm, and to seek the upstream regulatory genes. 
    RESULTS AND CONCLUSION: The intersection genes of the three biological functions of stem cell differentiation, osteoblast differentiation/osteoblast proliferation, and fibroblast proliferation are CDK6 and SFRP1. In the cascade regulatory pathway, there are three primary genes that can be used as the key genes for upstream regulation of periodontal reconstruction: bone morphogenetic protein 7, PAX2 and SMAD3, two secondary genes: RUNX2 and JUN, and two tertiary genes: ESR1 and GNAS. The upstream initiation genes are mostly involved in the process of osteoblast differentiation/ osteoblast proliferation. It is predicted that there are eight possible genes that play a key role in the periodontal reconstruction process: SFRP1, bone morphogenetic protein 7, PAX2, SMAD3, RUNX2, JUN, ESR1, GNAS. The periodontal reconstruction process is highly possible to start with cell osteogenesis, including osteoblast differentiation and osteoblast proliferation, followed by fibroblast proliferation.
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    Molecular mechanism by which miR-26b regulates fatty acid-binding protein 4-mediated adipocyte differentiation
    Na Risong, Sun Liang, Zhao Zhenqun, Liang Rong, Wang Xin
    2022, 26 (2):  260-265.  doi: 10.12307/2022.042
    Abstract ( 459 )   PDF (808KB) ( 58 )   Save
    BACKGROUND: The roles of miR-26b, PTEN-PI3K-AKT pathway and fatty acid-binding protein 4 (FABP4) in the process of adipocyte differentiation have been confirmed, but whether there is an interaction and their molecular mechanisms have not been reported yet.
    OBJECTIVE: To investigate the molecular mechanism by which miR-26b regulates FABP4-mediated adipocyte differentiation through the PTEN-PI3K-AKT pathway. 
    METHODS: 3T3-L1 preadipocytes were set as control group, 3T3-L1 cells maturely differentiated as differentiation group, 3T3-L1 cells transfected with miR-26b inhibitor as transfection group, and 3T3-L1 cells that were transfected with miR-26b inhibitor and then induced to differentiate were used as transfected differentiation group. Oil red O staining observed lipid droplets in mature adipocytes in the differentiation group and transfected differentiation group. Fluorescence quantitative PCR was used to detect the mRNA expression of miR-26b and FABP4, PTEN, PI3K and AKT in the cells. Western blot assay was used to identify the protein expression of FABP4, PTEN, PI3K and AKT in the cells. 
    RESULTS AND CONCLUSION: (1) The expression of miR-26b was significantly increased after 3T3-L1 cell differentiation (P < 0.05), suggesting that it may be involved in the regulation of cell differentiation. Inhibiting the level of miR-26b in the cells could inhibit the differentiation of 3T3-L1 cells into adipocytes and reduce the accumulation of intracellular lipid droplets. (2) The mRNA and protein expression of PI3K, AKT, and FABP4 in the 3T3-L1 cells increased significantly after differentiation (P < 0.01). Although PTEN mRNA expression increased (P < 0.05), the protein level did not change obviously (P > 0.05), suggesting that during the differentiation of 3T3-L1 cells, the PI3K-AKT pathway in the cells is activated and the level of FABP4 is increased. (3) Compared with normal differentiated cells, the mRNA and protein expressions of FABP4, PI3K, and AKT in differentiated cells in which the level of intracellular miR-26b was downregulated were significantly decreased (P < 0.01), while the mRNA and protein expressions of PTEN increased (P < 0.05), suggesting that inhibition of miR-26b significantly promoted mRNA and protein expression of PTEN, thereby inhibited PI3K-AKT pathway, reduced mRNA and protein expression of FABP4, and then inhibited 3T3-L1 cell differentiation.

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    N-6 methyladenosine RNA methylation regulates osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells
    Cao Wei, Mao Furong, Hu Xiaohua, Yang Xiaohong
    2022, 26 (2):  266-270.  doi: 10.12307/2022.043
    Abstract ( 383 )   PDF (759KB) ( 39 )   Save
    BACKGROUND: N-6 methyladenosine is one of the most common and abundant RNA modifications in eukaryotic mRNA. It modifies the base sites on gene fragments through methylation, affecting the biological functions of RNA such as translation, splicing, expression and degradation. Bone marrow mesenchymal stem cells, a kind of non-hematopoietic stem cells, have potential of multidirectional differentiation and show great application prospects in various bone-related diseases.
    OBJECTIVE: To summarize the functions and related mechanisms of various m6A modifying enzymes in osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells, and to briefly introduce the research methods and prospects of N-6 methyladenosine, so as to provide important reference for gene targeted therapy of bone metabolism-related diseases.
    METHODS: By searching several domestic and foreign literature databases, such as PubMed, Web of Science and CNKI. The key words were “m6A, bone marrow mesenchyml stem cell” both in English and Chinese. Finally, 46 articles were included for review. 
    RESULTS AND CONCLUSION: The occurrence of N-6 methyladenosine modification is mainly regulated by methyltransferase complex, demethylase and N-6 methyladenosine-specific protease. N-6 methyladenosine modifiers can affect the biological characteristics and functions of bone marrow mesenchymal stem cells at the gene level. There is a regulatory relationship between N-6 methyladenosine and signal transduction pathways related to osteogenic and adipogenic of bone marrow mesenchymal stem cells. N-6 methyladenosine has great potential in the field of bone marrow mesenchymal stem cells related regenerative medicine.  
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    Regulatory role of Keap1/Nrf2/ARE signaling pathway in bone homeostasis
    Wu Saixuan, Zhang Mi, Dong Ming, Lu Ying, Niu Weidong
    2022, 26 (2):  271-275.  doi: 10.12307/2022.044
    Abstract ( 964 )   PDF (646KB) ( 141 )   Save
    BACKGROUND: Recent studies have shown that the Keap1/Nrf2/ARE signaling pathway is closely related to the occurrence and development of bone destruction-related diseases. Targeted regulation of this signaling pathway can provide new ideas for clinical drug treatment of bone destruction-related diseases.
    OBJECTIVE: To review the research progress of Keap1/Nrf2/ARE signaling pathway in bone homeostasis.
    METHODS: WanFang and PubMed databases were searched for relevant articles published from January 1999 to October 2020. The retrieval key words were “Keap1/Nrf2/ARE signaling pathway, osteoclasts, osteoblasts, bone homeostasis” in Chinese and English, respectively. After removal of duplicate studies by reading the title and abstract, finally 50 articles were included in result analysis. 
    RESULTS AND CONCLUSION: Keap1/Nrf2/ARE signaling pathway is one of the important endogenous antioxidant defense mechanisms in cells. When activated, it can induce transcription of protective genes, maintain intracellular REDOX equilibrium, and protect cells and tissues from damage caused by oxidative stress. Activation of Keap1/Nrf2/ARE signaling pathway can inhibit osteoclast differentiation and bone resorption. The role of Keap1/Nrf2/ARE signaling pathway activation in osteoblasts remains controversial, which may be related to age and gender factors. This signaling pathway regulates bone homeostasis by mediating proliferation and differentiation of osteoclasts and osteoblasts.
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    The pivotal role of autophagy in bone cells: bone-related cell activity and bone metabolism
    Sun Youqiang, Ma Chao, Liang Mengmeng, Xin Pengfei, Zhang Hua, Xiang Xiaobing
    2022, 26 (2):  276-282.  doi: 10.12307/2022.045
    Abstract ( 597 )   PDF (720KB) ( 38 )   Save
    BACKGROUND: The importance of autophagy for maintaining cellular homeostasis and stress response has long been recognized. As a way for cells to selectively clear their damaged organelles to achieve the recycling of cellular components, autophagy has a pivotal role in bone metabolism. 
    OBJECTIVE: To review the role and possible mechanisms of autophagy in regulating bone-related cell activity and function among bone marrow mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. 
    METHODS: PubMed was searched for studies related to autophagy using the keywords of “autophagy; bone marrow mesenchymal stem cells; osteoblasts; osteocytes; osteoclasts.” 
    RESULTS AND CONCLUSION: We finally included 84 papers. Autophagy plays an important role in bone metabolism. Autophagy is involved in maintaining the balance between mineralization and absorption, and then maintaining bone homeostasis. An appropriate autophagy inducer may also benefit bone remodeling. Abnormal autophagy can lead to disorders of bone balance, leading to diseases such as osteoporosis. We may prevent or treat bone-related diseases by regulating the level of autophagy as its function in maintaining the balance of mineralization and resorption in bone homeostasis.
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    Expression and role of cannabinoid receptors during bone remodeling
    Fan Danyang, Fu Runze, Mi Jiajing, Liu Chunyan
    2022, 26 (2):  283-288.  doi: 10.12307/2022.046
    Abstract ( 497 )   PDF (733KB) ( 44 )   Save
    BACKGROUND: How cannabinoid receptors regulate the role of osteoblasts and osteoclasts and maintain the normal process of bone remodeling is of great significance for the normal development of bone, the maintenance of bone mass and the treatment of osteoporosis and periodontitis. 
    OBJECTIVE: To review the relationship between cannabinoid receptor and bone remodeling and its related factors, so as to provide ideas for the treatment of osteoporosis, periodontitis and other clinical applications.
    METHODS: We searched relevant articles published from July 2001 to July 2020 in PubMed, FMRS, CNKI, WanFang databases with the keywords of “endocannabinoid systems, the endocannabinoid receptors, osteoblasts, osteoclasts, bone mass, bone remodeling, oral health, osteoporosis, periodontitis” in Chinese and English, respectively. Finally, 77 articles met the criteria for review.
    RESULTS AND CONCLUSION: Bone remodeling depends on the interaction between osteoblasts and osteoclasts. The imbalance between bone resorption and bone formation will affect the process of bone remodeling and lead to bone inflammatory diseases such as osteoporosis and periodontitis. The endogenous cannabinoid system contains a variety of receptors, all of which belong to the G protein coupling superfamily. The two main receptors (cannabinoid type I and cannabinoid type II) are expressed in osteoblasts, osteoclasts and bone marrow mesenchymal stem cells and other bone-related cells. Under the action of natural ligands or synthetic agonists, cannabinoid receptors can produce specific physiological effects in vivo and in vitro through different metabolic pathways, thus regulating the generation and differentiation of osteocytes, and eventally affecting bone mass and bone metabolism. Further research on the mechanism of bone formation and bone loss has been a focus of current research, to provide new treatment ideas for the clinical work of bone-related diseases.
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    Mechanism of exercise improving bone metabolism in type 2 diabetics mellitus based on "Muscle-Bone" Crosstalk
    Zeng Xinyu, Chen Xianghe, Liu Bo, Lu Pengcheng, Jin Shengjie, Li Wenxiu, Tian Zhikai, Sun Changliang
    2022, 26 (2):  289-295.  doi: 10.12307/2022.047
    Abstract ( 532 )   PDF (733KB) ( 82 )   Save
    BACKGROUND: Type 2 diabetes mellitus is a disease caused by energy metabolism disorder. Muscles and bones participate in the body’s energy metabolism regulation through their endocrine function under the condition of exercise stimulation. Currently there are few studies on the mechanism of “Muscle-Bone” Crosstalk mediated exercise regulating bone metabolism in type 2 diabetes mellitus. 
    OBJECTIVE: By analyzing how exercise regulates the expression level of “Muscle-Bone” Crosstalk secretion-related factors and acting on the pathological reasons of bone tissue, to explore the mechanism of bone metabolism mediated by “Muscle-Bone” Crosstalk exercise in type 2 diabetes mellitus.
    METHODS: CNKI, WanFang, and PubMed were searched for relevant literatures published in recent 10 years. The keywords were “exercise, type 2 diabetes mellitus, bone metabolism, “Muscle-Bone” Crosstalk, muscle factor” in Chinese and English, respectively. After screening, 50 eligible articles were analyzed and discussed. 
    RESULTS AND CONCLUSION: Some of bioactive factors in muscles and bones act on the bones in an endocrine manner, such as myostatin, bone morphogenetic protein, musclin, etc., and the others act on the bones in a paracrine manner, such as insulin-like growth factor 1, interleukin 6, irisin, etc. These factors participate in the regulation of bone metabolism, balance the bone formation of osteoblasts and bone resorption of osteoclasts in bone tissue, and become the messenger factors of exercise-mediated musculoskeletal system. Exercise is an important means to regulate energy metabolism. Exercise-mediated internal stimulus changes can trigger the signal response of muscle cells and bone cells, activate Wnt, bone morphogenetic protein/Smads, transforming growth factor-β and other signal pathways, thereby regulating the endocrine function of the musculoskeletal system, promoting metabolic adaptation and influencing bone metabolism in type 2 diabetes mellitus. 

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    Greater trochanter pain syndrome: anatomy, pathology, differential diagnosis and treatment
    Zhang Chao, Lü Xin, Liu Jinyuan, Wang Xiaohu, Xu Xiaopei, Liu Zemin
    2022, 26 (2):  296-301.  doi: 10.12307/2022.048
    Abstract ( 1393 )   PDF (684KB) ( 138 )   Save
    BACKGROUND: Greater trochanter pain syndrome indicates a series of peritrochanteric space diseases that cause pain on the lateral side of the hip joint due to damage or pathological changes in the tissue structure around the greater trochanter of the femur. Although nonsteroidal anti-inflammatory drugs, corticosteroid injections, and physical therapy are effective in most patients, a significant number of patients still experience hip pain and functional limitations. 
    OBJECTIVE: To review the literature related to the anatomy, etiology, diagnosis and treatment of great trochanteric pain syndrome in recent years, providing evidence for clinical understanding and treatment of great trochanteric pain syndrome.
    METHODS: The databases of Medline and Embase were searched by compute using the keywords of “greater trochanteric pain syndrome, anatomy, etiology, diagnosis, imaging, treatment, surgical” in English. As per the inclusion criteria and exclusion criteria, 59 related literatures were finally included and summarized.
    RESULTS AND CONCLUSION: Greater trochanteric pain syndrome encompasses trochanteric bursitis, abductor tendinopathy (gluteus medius and gluteus minimus tendinopathy), and lliotibial tract friction syndrome. Abductor tendinopathy has been shown to be a major cause of pain. As a result, the efficacy of nonsteroidal anti-inflammatory drugs may be limited, while other non-surgical treatments, such as home exercise, extracorporeal shock wave therapy, and platelet-rich plasma, appear to be more effective. Non-surgical methods are the primary treatment for greater trochanteric pain syndrome. Open and endoscopic treatment options are available when nonsurgical treatment is unsuccessful.

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    Predictive value of blood biomarkers for brain injury after cardiac arrest
    Liu Xiaopeng, Zhang Sisen
    2022, 26 (2):  302-307.  doi: 10.12307/2022.049
    Abstract ( 396 )   PDF (673KB) ( 37 )   Save
    BACKGROUND: Neurological prognostication is crucial after cardiac arrest. To some extent, the blood biomarkers can help predict the neurological prognostication of brain injury after cardiac arrest.
    OBJECTIVE: To review the current advances in blood biomarkers of brain injury after cardiac arrest.
    METHODS: PubMed, CNKI, VIP and WanFang were searched for literatures related to the use of blood biomarkers for predicting brain injury after cardiac arrest. Keywords were “cardiac arrest, biomarkers, brain injury” in English and Chinese, respectively.
    RESULTS AND CONCLUSION: In recent years, various biomarkers have played an increasingly important role in the neurological prognostication of brain injury after cardiac arrest. Although many promising results have been achieved in new biomarkers, the thresholds for predicting poor outcomes of biomarkers vary greatly in different studies, indicating that no standardization requirements of these methods have been achieved. None of the measures assessed can predict adverse neurological outcomes with absolute certainty, and the multi-model approach still seems to be the most prudent prediction strategy. None of the evaluated indicators can be definitely absolute to predict adverse neurological outcomes, and the multi-modal approach still seems to be a prediction strategy that is most cautious. Conventional brain injury markers, such as neuron specific enolase and S100B, still have important advantages. Currently, further explorations on new blood biomarkers are warranted, and new breakthroughs can be achieved by more accurate outcome predictions in this field.
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    Guidelines for exercise during pregnancy in developed countries and revelation for the Healthy China Action
    Kan Jie
    2022, 26 (2):  308-314.  doi: 10.12307/2022.050
    Abstract ( 616 )   PDF (965KB) ( 110 )   Save
    BACKGROUND: A recent study on the relationship between regular exercise and maternal and newborn health variables found that regular exercise during pregnancy is negatively correlated with overweight fetuses, body mass of pregnant women at an older age, and pelvic pain. Observational studies on exercise during pregnancy have shown that its benefits include reduced gestational diabetes, cesarean section and surgical vaginal delivery, and postpartum recovery time.
    OBJECTIVE: To emphatically analyze the developmental history and characteristics of the guidelines for exercise during pregnancy in the United States, Canada, Australia and Britain and to provide references for promoting the establishment and implementation of China’s exercise guidelines for pregnancy based on actual conditions. 
    METHODS: CNKI, PubMed, ResearchGate and other databases were searched for relevant literatures using the following search terms: “pregnancy; exercise; guidelines; Healthy China; maternal and child health” for combined search. Finally, included literatures were categorized, analyzed and summarized.
    RESULTS AND CONCLUSION: After experiencing three stages of development and evolution in the 20th century and before, the early 21st century and after 2010, the guidelines for exercise during pregnancy in developed countries focus on physiological and anatomical changes during pregnancy and insist on the principle of disease prevention, take into consideration the situation multi-dimensionally, multi-levelly and multi-dimensionally, and use the method of evidence-based medicine to strengthen the guidelines scientifically, authoritatively, continually, roundly, accurately and timely. The revelations for the Healthy China Action are that: departments of government, health and sports should cooperate to develop and implement the guidelines for exercise during pregnancy for improving public awareness of exercise during pregnancy; from the view of the evidence-based medicine, information platform should be built to share, preach and train exercise prescription including pre-pregnancy, pregnancy and after delivery; develop the guidelines for exercise during pregnancy of varying health levels, exercise performance and ages, adding “avoiding sedentary behavior” and “increasing physical activity” as an important component of maternal and child health promotion action. 
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    Analgesic effect of adductor canal block versus femoral nerve block after autogenous bone-tendon-bone reconstruction of the anterior cruciate ligament: an updated Meta-analysis
    Diao Yulei, Zong Xiaorui, Deng Zhibo, Shu Han
    2022, 26 (2):  315-320.  doi: 10.12307/2022.051
    Abstract ( 582 )   PDF (723KB) ( 146 )   Save
    OBJECTIVE: Adductor canal block and femoral nerve block are common analgesic methods after anterior cruciate ligament reconstruction. This article systematically evaluates the analgesic effect of adductor tube block and femoral nerve block after anterior cruciate ligament reconstruction with autogenous bone-tendon-bone reconstruction.
    METHODS: A computer-based search was performed in PubMed, EMbase, Cochrane Library, Web of Science, Google Scholar, CNKI, WanFang, VIP and CBM databases for clinical  randomized controlled trials on the analgesic effect of femoral nerve block and adductor canal block from the establishment of the database to October 31, 2020 A randomized controlled clinical trial in analgesia after ligament reconstruction. The Cochrane risk bias table was used to assess the quality of the included literature. Meta-analysis was performed with RevMan 5.3 software, and the evaluation indicators included the main visual analog scale scores, opioid consumption and complications.
    RESULTS: A total of 6 randomized controlled trials involving 506 patients were included, 251 patients in the control group received femoral nerve block, and 255 patients in the intervention group received adductor tube block. The quality of the literature was higher. Meta-analysis showed that compared with the control group, the intervention group only had a slight advantage in reducing the visual analog scale score at 48 hours after surgery (mean difference=0.65, 95% confidence interval: 0.10-1.20, P < 0.05), but there was no significant difference between the two groups in terms of visual analog scores at 0, 6, 12, 18, and 24 hours postoperatively and morphine consumption at 0, 24, and 48 hours postoperatively (P > 0.05). Fewer complications, such as deep vein thrombosis, re-rupture of the anterior cruciate ligament, pain in the anterior knee area, defective knee extension function, decreased quadriceps muscle strength, and risk of falling, occurred in both two groups, indicating a high safety of two methods.
    CONCLUSION: There is basically no significant difference between femoral nerve block and adductor canal block in terms of postoperative analgesia, but large-sample randomized controlled trials are needed in the future to confirm the results. Adductor canal block is recommended in clinical practice due to its small inhibitory effects on the muscle strength of quadriceps muscle and no obvious complications.

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    Exercise improves pain induced by sciatic nerve injury in animal models: a Meta-analysis
    Sun Xinzheng, Chen Xiaoke, Wang Chenghao, He Hui
    2022, 26 (2):  321-328.  doi: 10.12307/2022.052
    Abstract ( 460 )   PDF (1230KB) ( 134 )   Save
    OBJECTIVE: Drug therapies have limited effect on neuropathic pain and result in many side effects. Comparatively speaking, exercise is a good way to relieve pain. Here, we systematically evaluate the interventional effect of exercise on neuropathic pain induced by sciatic nerve injury in rats and mice. 
    METHODS: WanFang, CNKI, PubMed, Embase and Web of Science databases were retrieved before April 2020. A series of studies regarding the effect of treadmill, swimming, wheel and other exercises on neuropathic pain induced by sciatic nerve injury in rats and mice were collected. According to the inclusion criteria, two researchers independently completed literature screening, data extraction and conducted methodological quality evaluation using SYRCLE’ s risk of bias tool for animal studies. RevMan 5.3 and STATA 12.0 analysis software were used for statistical analysis. 
    RESULTS:A total of 12 literatures regarding controlled animal studies were included, and there were 133 rodents in the exercise group and 135 rodents in the sedentary group. Meta-analysis showed that exercise could significantly increase paw withdrawal mechanical threshold [standard mean difference (SMD)=0.84, 95% confidence interval (CI): 0.28-1.40, P=0.003] and paw withdrawal thermal latency (SMD=1.54, 95% CI: 0.93-2.15), P < 0.000 01) in rats and mice after sciatic nerve injury. Subgroup analyses were performed for duration of exercise, indicating a significant reduction in heterogeneity. Postoperative exercise duration ≤ 3 weeks could significantly elevate paw withdrawal mechanical threshold (SMD=1.04, 95% CI: 0.62-1.46, P < 0.000 01). Postoperative exercise duration ≤ 4 weeks could significantly improve paw withdrawal thermal latency (SMD=1.93, 95% CI:1.19-2.67, P < 0.000 01).
    CONCLUSION: Exercise can effectively improve mechanical and thermal hypersensitivity caused by sciatic nerve injury in rats and mice. Pain models, exercise start point, exercise forms, and species are not the main factors of exercise-induced hypoalgesia, while postoperative exercise duration has an important influence on exercise-induced hypoalgesia.
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