BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

BACKGROUND:Cistanoside A has the effects of anti-inflammation,antioxidation,antioxidation,reducing renal damage and anti-osteoporosis,but its effect on osteoclast differentiation,function and its underlying molecular mechanisms remain unclear. OBJECTIVE:To investigate the effect of Cistanoside A on osteoclast differentiation and bone resorption induced by receptor activator of nuclear factor kappa-B ligand(RANKL)in vitro and its mechanism. METHODS:Bone marrow macrophages were obtained from the femur and tibia of 4-6-week-old C57BL/6 mice.The cytotoxic effect of Cistanoside A(5,10,20,40,80,and 160 μmol/L)on bone marrow macrophage viability was examined using the cell counting kit-8 assay kit.Tartrate-resistant acid phosphatase staining was performed to observe the effect of different concentrations of Cistanoside A on osteoblast differentiation and its effective intervention concentration was determined.There was positive control group,Cistanoside A low,medium,and high dose groups(40,80,and 160 μmol/L).After cell attachment,50 ng/mL RANKL was added to induce osteoblast differentiation,and the corresponding dose of Cistanoside A was added to the Cistanoside A low,medium,and high dose groups,respectively.F-actin ring and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride staining were performed to detect the effects of Cistanoside A on the formation of osteoclasts.Toluidine blue staining of bone abrasion slices was used to observe the effects of Cistanoside A on bone resorption function of osteoclasts.The expression of upstream and downstream proteins of the JNK/MAPK pathway was detected by Western blot.The expression of genes related to osteoclast differentiation and bone resorption function such as tartrate-resistant acid phosphatase,DC-STAMP,Nfatc-1,Ctsk and c-Fos was detected by RT-qPCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining,F-actin ring staining and resorption pit assay showed that Cistanoside A significantly inhibited RANKL-induced osteoclast differentiation and bone resorption in a dose-dependent manner compared with the positive control group.The results of RT-qPCR showed that compared with the positive control group,both high and low dose groups of Cistanoside A could significantly downregulate the mRNA expression of tartrate-resistant acid phosphatase,DC-STAMP,Nfatc-1,Ctsk and c-Fos in a dose-dependent manner.The results of western blot assay showed that the high dose group of Cistanoside A significantly inhibited the expression of p-JNK protein at 10,20,30 and 60 minutes of intervention;compared with the positive control group,Cistanoside A significantly inhibited the expression of Nfatc1 and c-Fos proteins in a dose-dependent manner.To conclude,Cistanoside A could inhibit the formation and bone resorption of osteoclasts by reducing the level of p-JNK protein,inhibiting the activation of MAPK pathway and the expression of key genes in osteoclasts.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

BACKGROUND:Stem cell transplantation is a novel therapy for myocardial infarction,but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect.Exercise preconditioning is a way to induce endogenous protective effects through exercise,which can be used as a new strategy for prevention and treatment of cardiac rehabilitation. OBJECTIVE:To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis. METHODS:Six-week-old male SD rats were randomly divided into control group,modeling group,stem cell group,and stem cell plus exercise group.Acute myocardial infarction model was made by coronary artery occlusion,and sham operation was performed in control group.The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling,and adipose-derived stem cell transplantation was performed 30 minutes after modeling.The stem cell group performed only adipose-derived stem cell transplantation.One and seven days after stem cell transplantation,the expression levels of myocardial total Akt(t-Akt),phosphorylated Akt(p-Akt),vascular endothelial growth factor(VEGF),total endothelial nitric oxide synthase(t-eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein were measured by western blotting,and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated.At 4 weeks after stem cell transplantation,the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system.Myocardial infarction area was measured by TTC staining.Myocardial interstitial collagen deposition was examined by Masson staining.Myocardial capillary density was detected by immunofluorescence staining,and myocardial apoptosis was measured by TUNEL staining. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:Compared with control group,left ventricular shortening fraction,left ventricular ejection fraction,myocardial capillary density,and myocardial blood flow decreased(P<0.05),myocardial infarction area,collagen volume fraction,and apoptosis increased(P<0.05)in the modeling group.Compared with the modeling group,the above indexes(except for left ventricular fractional shortening and left ventricular ejection fraction)in the stem cell group improved(P<0.05).Compared with the stem cell group,the above parameters were further improved in the stem cell plus exercise group(P<0.05).(2)One day after stem cell transplantation:Compared with the control group,the protein expression of t-Akt,p-Akt,VEGF,t-eNOS,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group(P>0.05).Compared with the modeling group,there were no significant changes in the above indexes in the stem cell group(P>0.05),and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group(P<0.05).(3)Seven days after stem cell transplantation:Compared with the control group,the protein expression of p-Akt,VEGF,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group(P<0.05).Compared with the modeling group,there were no significant changes in all parameters in the stem cell group(P>0.05),and the protein expression of p-Akt,VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group(P<0.05).These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction,and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

BACKGROUND:The morphological indexes of ankle point may change after ankle fracture,and there is a certain correlation between the coronal angle change of ankle point and the functional recovery of ankle joint.Most previous studies have studied the height recovery of ankle point after surgery,so the correlation between the fluctuation of coronal angle of ankle point and the functional recovery of ankle joint after ankle fracture has certain reference significance. OBJECTIVE:To investigate the effect of coronal angle change of ankle point on joint function recovery after ankle fracture. METHODS:A total of 86 patients with ankle fracture who underwent surgical treatment were selected as the study objects,and were divided into excellent group(n=45)and poor group(n=41)according to the results of American Orthopaedic Foot&Ankle Society(AOFAS)hindfoot-ankle score during the last follow-up,and the general data of the two groups were compared.The morphological indexes of ankle points on the affected side and healthy side were compared after surgery based on ankle acupoints and lateral X-rays of the ankle joint,including the width and depth of ankle points,coronal angle and sagittal angle,and the difference of ankle points between the affected side and healthy side,and further comparison and analysis were conducted in each group.A joint model was constructed and Cox regression analysis was used to evaluate the relationship between coronal angle fluctuation and joint function recovery.Least absolute shrinkage and selection operator regression method and multivariate Logistic regression were used to analyze the risk factors affecting the recovery of joint function.The patients were divided into 5-quartile array(Q1-Q5)according to the angle of coronal position at ankle point from low to high.The clinical data characteristics of the five groups were compared,and the correlation between the change of coronal position at ankle point and the risk of poor recovery of joint function was analyzed by multivariate Logistic regression.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship.The prediction model of regression equation y=1-1/(1+e-z)was established and verified. RESULTS AND CONCLUSION:(1)The width and depth of ankle point on the affected side,coronal angle and sagittal angle were significantly higher than those on the healthy side(all P<0.05),and compared with the excellent group,the difference of ankle point width,depth difference,coronal angle difference and sagittal angle difference were greater in the poor group(P<0.05).(2)The combined model showed that the risk of poor joint function was increased by 3%for every 1? increase in coronal angle,regardless of whether the angle was within the normal range.(3)Least absolute shrinkage and selection operator regression and multivariate Logistics regression analysis showed that after adjusting for potential confounding factors,it was found that age,lack of functional exercise in early stage,no calcaneal traction,failure to remove internal fixation,postoperative complications,and increased ankle coronal angle were independent risk factors for joint function recovery(P<0.05).(4)The coronal angle within 3 months after surgery was independently correlated with the risk of poor joint function recovery(OR=1.57,95%CI:1.38-1.76,P=0.002),and the trend test of the coronal angle from low to high quintile in each postoperative period had statistical significance(Ptrend<0.001).(5)Restricted cubic spline model analysis showed that there was no nonlinear relationship between the coronal angle change of ankle point and the risk of poor joint function recovery in males or females.Through Bootstrap self-sampling,the prediction model has good differentiation and accuracy.(6)The reduction of coronal angle of ankle point after ankle fracture plays a significant role in promoting the recovery of joint function.Therefore,the detection of coronal angle of ankle point after ankle fracture is helpful to understand the recovery of joint function of patients.

Objective: To evaluate the accuracy of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) in screening true obesity among children, so as to provide a scientific basis for precise screening and early prevention and control of childhood obesity. Methods: A total of 1 322 children aged 10-15 years old were surveyed by the Huantai Children Cardiovascular Health Cohort in 2021. Fat mass percentage (FMP) and fat mass index (FMI) were measured by bioelectrical impedance analysis, with FMP or FMI values at or above the age and sex-specific 70th percentiles as the criteria for defining true obesity. BMI, WC and WHtR were used to define general obesity and central obesity. The accuracy of these measures in screening for true obesity was evaluated by calculating the missed diagnosis rate, misdiagnosis rate, area under the curve(AUC) for receiver operating characteristic and Kappa coefficient. Results: Boys had higher BMI [(21.79±4.56) kg/m 2], WC [(76.41±12.53) cm] and WHtR (0.47±0.07) than girls [(20.83±4.13) kg/m 2, (70.69±10.06) cm, (0.45±0.06)] ( t =4.02, 9.19, 6.63), while boys had lower FMP [(18.29±8.35)%] and FMI [(4.35±2.79) kg/m 2] than girls [(24.87±6.51)%, (5.44±2.53) kg/m 2] ( t =-16.10,-7.42) ( P <0.01). Using FMP as a reference standard, the diagnosis error rates of screening for true obesity based on BMI, WC and WHtR were 12.24%, 2.11% and 2.11%, respectively; the diagnosis error rates were 10.88%, 27.28% and 24.33%; the AUC values were 0.88, 0.85 and 0.87; the Kappa coefficients were 0.67, 0.48 and 0.52. Using FMI as a reference standard, rates of BMI, WC and WHtR screening for true obesity were 14.20%, 1.23% and 2.78%; the diagnosis error rates were 4.81%, 20.84% and 18.14 %; the AUC values were 0.90, 0.89 and 0.90; the Kappa coefficients were 0.81, 0.64 and 0.67. Conclusions BMI has a higher diagnosis error rate in screening for true obesity in children, while WC and WHtR have higher diagnosis error rates. It is recommended to promote body fat assessment in clinical practice, so as to achieve more accurate prevention and control of chronic diseases.

Background When live working line operators engage in upper limb operations, working for a long time with raising arms and the exposure to adverse ergonomic factors tend to increase muscle load, cause fatigue accumulation, and increase the risk of work-related musculoskeletal disorders (WMSDs). Objective To analyze work posture and associated muscle fatigue during executing breaking/connecting contact terminal, and identify adverse ergonomic factors of the work process. Methods This study recruited 10 volunteers to perform breaking/connecting contact terminal simulation. At a distance of 4.5, 3.5, and 2.5 m from the body to the wire, each performed the task 5 times. Visual 3D was used to analyze the kinematic data from motion capture. The surface electromyography (sEMG) signals of the deltoid, biceps, triceps, and brachioradialis were recorded during the simulation and analyzed for muscle fatigue using root mean square (RMS), median frequency (MF), and jointed EMG amplitude and spectrum analysis (JASA). After completion of each task, Borg scale was used to query the volunteers of their subjective fatigue. A 2-min rest was required between each distance. Results The kinematic data from motion capture showed that in the entire process of the task, the right upper limb was higher when lifting, with the right shoulder joint maintaining flexion and fluctuating periodically between abduction and adduction, external and internal rotation, the right elbow joint maintaining flexion and supination. The frequency of task cycle showed a significant effect on the Borg scale scores (P<0.001, partial \begin{document}$ {\eta }^{2} $\end{document}=0.464); the distance showed no significant effect on the Borg scale scores (P>0.05, partial \begin{document}$ {\eta }^{2} $\end{document}=0.002); their interaction effect was not significant (P>0.05, partial \begin{document}$ {\eta }^{2} $\end{document}=0.020). The results of the sEMG signals showed that at a distance of 4.5 m, the volunteers had the highest percentages of maximal voluntary electrical activation (MVE%) in the deltoid and right brachioradialis and the lowest MF values in the deltoid and left brachioradialis after completing 5 task cycles. The results of JASA showed that fatigue was observed in brachioradialis and deltoid after completing 5 task cycles at a distance of 4.5 m, the right deltoid and right brachioradialis at a distance of 3.5 m, in the brachioradialis, deltoid, and left bicep at a distance of 2.5 m. Conclusion The subjective fatigue of workers who engaged in breaking/connecting contact terminal elevates with more repetitive operations. Based on the sEMG and motion capture analysis, it can be found that improper distance between the workers and the target work area can increase the burden from poor posture and improper use of work equipment, and lead to muscle fatigue; the deltoid and brachioradialis are the key muscles of fatigue in this type of operation; changing the angle of the elbow joint and the shoulder joint during the process of the operation can affect the deltoid and brachioradialis exertion and loading.

Background Power grid is an important component of the national infrastructure. The occupational health issues among the workers in this industry are attracting great concern nationwide. Objective To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in neck and shoulder among the power distribution workers of power supply enterprises, and analyze the related influencing factors. Method In April 2023, a total of 1244 workers in 50 municipal power supply bureaus were randomly selected from the three provinces under China Southern Power Grid using cluster sampling method. The questionnaire used in the study was based on a revised Musculoskeletal Disorders Questionnaire and added ergonomic load of upper limb work. \begin{document}$ {\chi }^{2} $\end{document} test and logistic regression model were used to explore the influencing factors of neck pain and shoulder pain among the subjects. Results A total of 1244 valid questionnaires were recovered and the effective recovery rate was 90.87%(1244/1369). The positive rates of neck pain and shoulder pain were 45.5% (566 cases) and 36.3% (452 cases) respectively. The logistic regression analysis results showed that more than 20 years working age (OR=2.27, 95%CI: 1.39, 3.96; OR=2.56, 95%CI: 1.53, 4.26), often (OR=2.08, 95%CI: 1.35, 3.20; OR=2.40, 95%CI: 1.50, 3.58)/quite often (OR=2.96, 95%CI: 1.73, 5.04; OR=2.72, 95%CI: 1.49, 4.94) maintaining a forced posture, and working immediately after break (OR=1.72, 95%CI: 1.04, 2.85; OR=2.14, 95%CI: 1.19, 3.88) were associated with a higher positive rate of neck pain and shoulder pain respectively. Feeling sufficient rest (OR=0.61, 95%CI: 0.47, 0.80; OR=0.63, 95%CI: 0.50, 0.83) and opportunity to decide when to take breaks (OR=0.72, 95%CI: 0.53, 0.98; OR=0.62, 95%CI: 0.41, 0.93) were associated with a lower positive rate of neck pain and shoulder pain respectively. Conclusion The positive rates of neck pain and shoulder pain are high among power distribution workers. The main influencing factors included long working age, quite often maintaining a forced posture, and working immediately after break.

Irritable bowel syndrome (IBS) is an extremely common chronic intestinal disorder characterized by recurrent abdominal pain and altered bowel habits, significantly impacting patients' quality of life. The etiology of IBS remains incompletely understood. Research has identified low-grade intestinal inflammation and immune activation, primarily manifested as an imbalance between pro-inflammatory and anti-inflammatory cytokines, as key pathogenic mechanisms in IBS. Among these, interleukin-6 (IL-6), a core pro-inflammatory cytokine, is significantly elevated in IBS patients. IL-6 contributes to the pathogenesis of IBS through various mechanisms, including altering individual susceptibility to IBS, promoting gastrointestinal motility and secretion, activating the hypothalamic-pituitary-adrenal axis, inducing visceral hypersensitivity, and impairing intestinal mucosal barrier function. Furthermore, IL-6 levels are closely associated with the severity of IBS symptoms. This review summarizes the role and mechanisms of IL-6 in IBS, aiming to provide insights and references for clinicians and researchers investigating the etiology of IBS.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.