AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P＜0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P＜0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P＜0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0～80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P＜0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.

BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0～40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P＜0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P＜0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P＜0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Background Hand arm vibration disease (HAVD) is one of the legal occupational diseases in China, and its pathogenesis is not clear. Operators exposed to electric vibration tools for a long time have an increased risk of HAVD. Objective To conduct a systematic evaluation of the effects of vibration operations on workers' upper limb nerves, blood vessels, and muscles. Methods Relevant studies on the effects of hand-transmitted vibration on HAVD were searched and collected from the China Knowledge Infrastructure, Wanfang, and PubMed databases, and the literature was published from January 1974 to April 2021. The quality of cohort and case-control studies was assessed by the Newcastle-Ottawa Scale (NOS), and the quality of cross-sectional studies was by the evaluation criteria recommended by the Agency for Healthcare Quality and Research (AHRQ). Statistical analyses of outcome indicators (OR) in the included literature were performed using RevMan 5.4.1 software, effect sizes in the literature on vibration-induced white finger and neurosensory impairment were combined using a random-effect model, those that included carpal tunnel syndrome were combined using a fixed-effect model, and subgroup and publication bias analyses were also performed. To explore sources of study heterogeneity, meta-regression was performed using Stata 16.0 software, and sensitivity analyses were performed on the included literature. Results A total of 716 papers were retrieved from the databases, and 18 articles were retrieved by manual searching. A total of 34 papers were included after excluding those not meeting the criteria. Of the papers, 11004, 7270, and 1722 subjects related to vibration-induced white finger, neurosensory impairment, and carpal tunnel syndrome, respectively. The results of meta-analysis showed that compared with the control group, the combined ORs of hand-transmitted vibration exposure were 4.25 (95%CI: 2.72−6.65) for vibration-induced white finger, 4.03 (95%CI: 2.46−6.61) for neurosensory impairment, and 2.44 (95%CI: 1.61−3.71) for carpal tunnel syndrome. Heterogeneity was identified in the original studies related to vibration-induced white finger (I²=81%, P < 0.001) and neurosensory impairment (I²=90%, P < 0.001), except carpal tunnel syndrome (I²=23%, P < 0.001). The results of sensitivity analysis showed that the combined effect sizes (ORs) were stable and reliable. The results of meta-regression showed that the factors contributing to high heterogeneity of combined vibration-induced white finger and neurosensory impairment were time of publication (t=−2.10, P=0.049) and working age (t=−2.40, P=0.032), respectively. Conclusion Hand-transmitted vibration is a risk factor for vibration-induced white finger, neurosensory impairment, and carpal tunnel syndrome in operators.

Objective To study the effect of gender and maneuvers on anterior cruciate ligament (ACL) injury risk factors for volleyball players. Methods Sports biomechanics data of volleyball players during stop-jump, drop landing and sidestep cutting were collected. The ACL injury rate and biomechanical parameters of simulated injured jumps were obtained with Monte Carlo simulation. The influence of gender and maneuvers on ACL injury risk factors was validated by 2×3 mixed designed two-way ANOVA. Results Sidestep cutting was the highest risk maneuver of ACL injury for both genders (P＜0.001). Compared with male players, female players had a greater risk of ACL injury during sidestep cutting and stop-jump (P＜0.001), while male players were more prone to have ACL injury than female players during drop landing (P＜0.001). The risk factors of ACL injury obtained by simulation were significantly influenced by gender and maneuvers (P＜0.001). Conclusions Male players were more likely to increase ACL load due to smaller knee flexion, forward leg tilt and heel landing than female players during sidestep cutting, while female players owned larger ground reaction force (GRF) and knee extension moment. Smaller knee flexion angle during stop jump was the major risk factor for both genders, however more characteristics contributed to the males. Female players with large GRF, knee valgus and extension moment, and heel-landing were likely to have ACL injury, while the small knee flexion angle was the key risk factor for male players. The results can provide evidences for evaluation of volleyball players’ ACL injury risk, individualized injury prevention protocols, and clinical treatment and rehabilitation directions.

Objective: To explore the correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students. Methods: 22 628 middle school students in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang were enrolled by multistage cluster sampling method from November 2015 to January 2016. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and Multidimensional Sub-health Questionnaire of Adolescents (MSQA) were applied to acquire basic characteristics, health literacy, mobile phone use dependence and psychopathological symptoms of subjects. Subjects were classified into three groups, low level (<P₂₅), medium level (P₂₅-P₇₅) and high level (>P₇₅), according to the percentile of the questionnaire score. Multivariate logistic regression model was used to analyze the correlation of health literacy, mobile phone with psychopathological symptoms. Results: The students were (15.4±1.8) years old with 10 990 boys (48.6%). The score of health literacy of students were (104.1±18.7) points. The rate of mobile phone use dependence was 25.4% (5 752/22 628) and the rate of psychopathological symptoms was 29.1% (6 581/22 628). Compared with high health literacy level, medium and low health literacy levels were related to psychopathological symptoms, with OR (95%CI) about 2.30 (2.10-2.52) and 5.40 (4.89-5.97), respectively. Compared with mobile phone use independence, mobile phone use dependence was related to psychopathological symptoms, with OR (95%CI) about 3.60(3.37-3.85). The highest rate of psychopathological symptoms occurred in students with mobile phone use dependence and low health literacy level [68.0% (1 345/1 977)], with OR (95%CI) about 19.59 (17.07-22.48). Conclusion Health literacy and mobile phone use dependence are related factors of psychopathological symptoms in middle school students.

Objective: To explore the association between co-consumption of takeaway fast foods and sodas with depressive symptoms among Chinese adolescents, and to provide a reference for reducing the occurence of depression among adolescents. Methods: A multi-center population-based survey was conducted in 32 schools in 4 provinces across China. A total of 14 500 adolescents completed eligible questionnaires. Depressive symptoms were assessed by using Children’s Depression Inventory(CDI), while consumption of takeaway fast foods and sodas was collected using the semi-quantitative Food Frequency Questionnaire(FFQ). Results: 27.26%(3 952/14 500) of adolescents were reported of depressive symptoms. The low, middle, and high-frequency consumption of takeaway fast foods (a OR=1.12, 1.73, 1.56, P<0.05) and sodas (a OR=1.64, 2.17, 3.54, P<0.01) were associated with depressive symptoms, and dose-response relationships were observed in all association(P<0.01). Meanwhile, positive additive interactions were observed in the association(a OR=2.46, P<0.01). The relative excess risk, attribution ratio and the interaction index of synergy was 0.45(0.12-0.77), 0.18(0.06-0.30) and 1.44(1.10-1.89), respectively. Conclusion Co-consumption of takeaway fast foods and sodas significantly associates with depressive symptoms by synergistic effect among Chinese adolescents.

Objective: The present study aimed to determine the prevalence of childhood abuse and examined its correlation with inflammatory factor IL-6 level in middle schools students. Methods: A total of 911 junior and high school students from a middle school in Shenyang were enrolled in this study to investigate the experience of childhood abuse and its association with IL-6 level in fasting blood samples in December 2017. Results: The prevalence of childhood maltreatment was 21.0%, the prevalence of physical, emotional and sexual abuse was 21.8%, 20.3% and 9.5%, respectively. Physical abuse, emotional abuse and total abuse were associated with high levels of IL-6 in junior high school boys, χ2 values were 3.88, 6.78, and 9.10, respectively (P<0.05). There was no significant correlation between abuse experiences with IL-6 levels among junior high school girls and senior high school students. Regression analysis showed that physical abuse, emotional abuse and total abuse were positively associated with IL-6 concentration among junior high school boys(OR=2.23, 3.49, 1.58, P<0.05). Conclusion Physical and emotional abuse in childhood associates with the increase of IL-6 level among junior school boys. Abnormal inflammatory factor level might be potential mechanism linking childhood abuse with adverse health outcomes.