BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

BACKGROUND:The specific molecular mechanisms underlying common degenerative bone diseases,such as osteoarthritis,osteoporosis,and intervertebral disc degeneration,are currently unclear and may involve endoplasmic reticulum stress.At present,research on the systematic role of endoplasmic reticulum stress in the pathogenesis of these common skeletal diseases and related therapeutic progress is relatively limited. OBJECTIVE:To review the role of endoplasmic reticulum stress in common degenerative bone diseases,explore the molecular mechanisms of these diseases in depth,and provide new ideas and perspectives for prevention and treatment of these diseases. METHODS:Relevant literature from 2000 to 2024 was searched in CNKI,WanFang,VIP,PubMed and Web of Science databases using the search terms of"endoplasmic reticulum stress,bone disease,unfolded protein response,osteoarthritis,osteoporosis,intervertebral disc degeneration,autophagy,apoptosis,ferroptosis,pyroptosis"in Chinese and English.After removal of duplicates and older literature,a total of 115 articles met the inclusion criteria. RESULTS AND CONCLUSION:Endoplasmic reticulum stress has a dual effect in regulating cell physiology.Mild endoplasmic reticulum stress promotes osteogenic differentiation and extracellular matrix synthesis;however,persistent excessive endoplasmic reticulum stress leads to cell death.Endoplasmic reticulum stress-induced cell autophagy and apoptosis are closely related to osteoarthritis,osteoporosis,and intervertebral disc degeneration.Aging,drug side effects,metabolic disorders,calcium imbalance,poor lifestyle habits and other reasons may lead to long-term activation of endoplasmic reticulum stress,which causes bone remodeling disorders,cartilage damage,nucleus pulposus cell death and other pathological manifestations,ultimately leading to the occurrence of osteoarthritis,osteoporosis and intervertebral disc degeneration.Intervention in the relevant mechanisms triggering endoplasmic reticulum stress is expected to play a role in the prevention and treatment of common degenerative bone diseases,such as osteoarthritis,osteoporosis and intervertebral disc degeneration.

BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

OBJECTIVE:High-intensity interval training(HIIT)and moderate-intensity continuous training(MICT)can improve the quality of life of patients with clinical chronic diseases,but their application effects and regulatory factors in adults with insufficient physical activity are still unclear.This study aimed to explore the application effects and regulatory factors of HIIT and MICT on the quality of life of adults with insufficient physical activity. METHODS:A systematic literature search was conducted in databases including Web of Science Core Collection,Medline(EBSCO Host),PubMed,and Cochrane Library.The search time limit was from the establishment of each database to September 2023.The types of included literature were randomized controlled trials,and the research subjects were physically inactive adults.RevMan 5.4 software and the GRADE evidence evaluation framework were used to assess the quality of the included literature.Main effects pooling of random effects models was performed using R Studio(version 4.2.0).Subgroup analyses,regression analyses,and sensitivity analyzes were used to explore the sources of study heterogeneity and moderators. RESULTS:(1)Thirty-two randomized controlled trials of moderate to high quality were included,involving 2 083 physically inactive adults(HIIT group n=474;MICT group n=708;control group n=901).(2)Compared with the non-training control group,HIIT[Hedges'g=0.61;95%confidence interval(CI):0.40-0.83;I2=45%]and MICT(Hedges'g=0.66;95%CI:0.25-1.08;I2=89%)significantly improved the quality of life.Direct comparison studies of HIIT and MICT found no significant differences in the quality of life(Hedges'g=-0.01;95%CI:-0.23-0.21;I2=0%).(3)Subgroup analysis showed that HIIT and MICT were more effective in improving the physical components of the quality of life(HIIT:Hedges'g=0.82 vs.0.75;MICT:Hedges'g=0.74 vs.0.55),while cycling had a better trend in improving overall quality of life(HIIT:Hedges'g=0.74 vs.0.36;MICT:Hedges'g=1.08 vs.0.52).(4)Additionally,regression analysis did not identify any significant moderators(P>0.05 for all factors).(5)None of the above meta-analyses found publication bias(Egger test P>0.05). CONCLUSION:(1)Moderate to high level evidence shows that both HIIT and MICT can improve the quality of life of adults with insufficient physical activity,and the intervention effects between the two are similar.Therefore,when choosing between these two options,it is necessary to comprehensively consider factors such as time economy,scheduling flexibility,and application feasibility to formulate a personalized exercise plan.(2)This study recommends that when applying HIIT,a low-volume protocol(for example,5 groups each time,1 minute each),3 times/week,and ride at 80%-95%of the maximum heart rate is used to achieve the theoretical best improvement effect.(3)Although MICT improves the quality of life,there is insufficient evidence that increasing exercise duration brings additional benefits.Therefore,this study recommends that when MICT is conducted,it should be carried out more than three times a week,with each training duration controlled between 25 and 60 minutes,and cycling at 50%-75%of the maximum heart rate,in order to achieve the theoretically expected best improvement effect.

Objective: To explore the relationship between visual acuity and physical fitness of university freshmen, so as to provide reference for myopia prevention and control for freshmen. Methods: From October to November 2022, 2 160 college freshman without majoring in public safety administration, selected from Guangxi Police College in 2022 by using the stratified cluster random sampling method, were reviewed for the results of visual acuity test and physical fitness scores. The physical fitness indices were evaluated by using the Z scores of physical fitness test scores, and the strength of association between the level of physical fitness index and myopia was analyzed by using Logistic regression model. Results: Among 2 160 college freshman without majoring in public safety administration, 917 (42.5%) students were diagnosed screening myopia, including 66 (3.1%) cases of high myopia, 383 (17.7%) cases of moderate myopia and 468 (21.7%) cases of mild myopia. The differences in the distribution of visual acuity tests among students with different physical fitness indices, body mass index, and gender were statistically significant ( Z/H=54.50, 49.53, 15.51, P <0.01). Low level and low middle level physical fitness indices were associated with screening myopia among freshmen[ OR (95% CI )=2.81(1.93-4.08),1.87(1.38-2.54)], and low level physical fitness indexes were associated with high myopia [ OR (95% CI )=7.22(2.33-22.32)] ( P <0.01). Conclusions Screening myopia among college freshman without majoring in public safety administration is related to physical fitness, and low level and low middle level physical fitness index are risk factors for myopia. Improving the level of physical fitness might be effective in preventing myopia.

Objective: To construct a scientific and perfect evaluation index system of infectious disease prevention and control ability in colleges and universities, so as to provide reference tools for colleges and universities to effectively respond to infectious disease. Methods: The initial framework of the evaluation index system of infectious disease prevention and control ability in colleges and universities was constructed by using literature analysis method. Experts familiar with infectious disease prevention and control or school health work were selected to conduct two rounds( n =16，18) of Delphi expert consultation for determining the evaluation index system. Analytical hierarchy process was used to calculate the index weights and combined weights. About 198 prevention and control personnel were conveniently selected from 3 universities in Inner Mongolia Autonomous Region to comprehensively evaluate the evaluation indicators by using fuzzy comprehensive evaluation method. Results: After two rounds of Delphi consultation questionnaire, the effective recovery rates were 80.0% and 90.0%, the expert authority levels were 0.89 and 0.86, the expert harmony coefficients for Kendall W were 0.166 and 0.310, and the variation coefficient of each index was <0.25. Finally, the evaluation index system of infectious disease prevention and control ability of colleges and universities included 4 first level indicators, 14 second level indicators and 75 third level indicators. The weights of prevention and monitoring and early warning, organizational system guarantee, emergency management, rehabilitation and summary were 0.176, 0.476, 0.268 and 0.080, respectively. The top 3 weights of the secondary indexes were 0.623 for infectious disease surveillance and early warning, 0.595 for loss assessment and 0.370 for emergency response. The score of fuzzy comprehensive evaluation of the index system of infectious disease prevention and control ability in colleges and universities was 79.148, suggesting a high level. Conclusion The established evaluation index system of infectious disease prevention and control ability in colleges and universities is scientific and reasonable, which is conducive to provide tool reference for the evaluation of infectious disease prevention and control ability in colleges and universities.

Background Prior epidemiological studies suggest that exposure to pyrethroid insecticides may adversely affect children’s respiratory health. However, only limited studies are currently available on this topic in China. Objective To explore the association between exposure to pyrethroid insecticides and pulmonary function in children in Shanghai. Methods From August 2019 to January 2020, a cross-sectional study was conducted, recruiting 163 healthy school-aged children (aged 5–12 years) from Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine. Basic information, including age, height, weight, and family income, was collected. Urine samples from the children were collected and were analyzed for the levels of three pyrethroid insecticide metabolites: 3-phenoxybenzoic acid (3-PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA). Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used for the analysis. Spirometry was used to assess pulmonary function and recorded following parameters: peak expiratory flow (PEF), forced expiratory flow between the 25th and 75th percentiles of forced vital capacity (FEF_25-75), forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC. Multiple linear regression and restricted cubic spline models were used to evaluate the associations between urinary pyrethroid insecticide metabolite levels and pulmonary function parameters. Results The study included 163 school-aged children, with an average age of (7.04 ± 2.08) years and an average body mass index (BMI) of (16.04 ± 2.72) kg·m⁻²; 75 (46.01%) of the participants were boys. The detection rates of 3-PBA, TDCCA, and CDCCA in urine were 85.28%, 17.79%, and 4.91%, respectively. The median creatinine-adjusted 3-PBA concentration was 0.150 μg·g⁻¹. After adjusting for confounders such as height, BMI, sex, age, delivery mode, annual family income, and maternal education level, the multiple linear regression model showed that urinary 3-PBA levels were negatively associated with both FVC [β=−0.030, 95% confidence interval (CI): −0.058, −0.003; P=0.031] and FEV₁ (β=−0.032, 95%CI: −0.064, 0.000; P=0.04998). The final restricted cubic spline model showed a nonlinear association between urinary 3-PBA levels and FVC, FEV₁, PEF, and FEF_25-75（P for nonlinear < 0.05；P for overall < 0.05）. Conclusion The level of pyrethroid insecticide exposure in school-aged children in Shanghai is relatively high. The urinary 3-PBA concentration is negatively associated with pulmonary function, indicating potential adverse effects of pyrethroid insecticide exposure on respiratory health of school-aged children.

Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

AIM: To analyze the prevalence, severity, types, and correction of astigmatism in children, and provide scientific evidences for the prevention and treatment of refractive errors.METHODS: This cross-sectional study included 29 153 children aged 6-12 years from Xi'an and Lantian County, Shaanxi Province, China. Visual acuity and non-cycloplegic refraction were measured. Astigmatism was defined as an absolute cylindrical power ≥0.5 D in the right eye. Differences in astigmatism severity, type distribution, and refractive correction were analyzed across age, gender, and region.RESULTS:The prevalence of astigmatism increased with age, peaking at 11 years old(62.88%). Boys(57.10%)had a higher prevalence than girls(54.86%), and the municipal areas(58.29%)had a higher prevalence than county areas(51.75%). Mild astigmatism was the most common(63.82%), with moderate astigmatism increasing with age. The highest prevalence of high astigmatism was observed in 11-years-old children(9.68%). Compound myopic astigmatism(59.28%)and mixed astigmatism(25.16%)were the most frequent types. With increasing age, compound myopic astigmatism increased, while simple myopic, simple hyperopic, and compound hyperopic astigmatism decreased. Mixed astigmatism increased from ages 6 to 7, but declined from ages 7 to 12. For astigmatic axis types, with-the-rule astigmatism was the most prevalent(81.06%)and increased with age, peaking at 11 years(85.74%). Against-the-rule astigmatism showed a declining trend, while oblique astigmatism remained relatively stable. Distribution differences in astigmatism types and axes by gender and region were observed. Significant differences in astigmatism severity, types, and axis types across different ages, genders, and regions were observed(all P<0.05). The overall refractive correction rate for children with astigmatism was only 40.18%.CONCLUSION: The overall prevalence of astigmatism among children aged 6-12 years in Shaanxi Province was 56.02%, with higher prevalence observed in boys and in municipal areas. Age, gender, and region significantly influenced the prevalence of astigmatism. Notably, less than half of the children with astigmatism received refractive correction, highlighting the need for increased attention from parents and relevant authorities.

AIM: To compare the application of two distinct suspension suture fixation techniques in intraocular lens implantation.METHODS: Retrospective study. A total of 60 patients(60 eyes)who underwent intraocular lens suspension surgery at ophthalmology department of our hospital between January 1, 2021, and December 1, 2023 were included. Patients were divided into two groups based on the suturing techniques: the control group(n=30)received sub-scleral flap suture fixation, while the intervention group(n=30)underwent Z-shaped suture fixation. A 6 mo postoperative follow-up was conducted to assess surgical duration, visual acuity and quality, ocular structure, clinical efficacy, postoperative expose rate of sutures, diopters and decentration of intraocular lens.RESULTS:The mean operative time was significantly longer in the intervention group(50.5±3.1 min)compared to the control group(40.9±2.8 min; P<0.01). At 6 mo postoperatively, both groups demonstrated significant improvements in uncorrected and best-corrected visual acuity compared to preoperative values(both P<0.01), and there were no statistically significant differences in the uncorrected and best corrected visual acuity between the two groups(all P>0.05); at 6 mo postoperatively, the visual quality of the intervention group was better than that of the control group(P<0.05). While both groups exhibited a significant reduction in corneal endothelial cell count postoperatively(both P<0.01), there was no significant difference between the groups(P>0.05). The overall efficacy rate and suture exposure rate were comparable between the groups at 6 mo postoperatively(P=0.542 and P>0.05, respectively). However, significant differences were observed in postoperative diopters and intraocular lens decentration between the two groups(both P<0.01).CONCLUSION:Although both suture fixation techniques yielded satisfactory clinical outcomes in intraocular lens implantation, the Z-shaped suture fixation demonstrated superior performance in terms of visual quality and preservation of ocular structural integrity.