BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

OBJECTIVE To investigate the mechanism through which Danggui buxue decoction regulates neutrophil extracellular traps （NETs） to improve osteoporosis （OP） in rats with premature ovarian failure （POF）. METHODS Female SD rats were randomly divided into normal group， model group， calcitriol group， and Danggui buxue decoction low-dose， medium-dose and high-dose groups， with 9 rats in each group. Except for the normal group， all other groups were administered cisplatin via intraperitoneal injection on days 1 and 8 to establish a POF complicated with OP model. Each group received the corresponding drugs or normal saline intragastrically starting from day 5， once a day， for 4 consecutive weeks. After the last medication， serum levels of estradiol （E2）， NETs， 25-hydroxyvitamin D3 [25（OH）D3]， receptor activator of nuclear factor-κB ligand （RANKL）， and osteocalcin （BGP） were measured. The histopathological changes in bone tissue were observed. The expressions of vitamin D receptor （VDR）， myeloperoxidase （MPO）， neutrophil elastase （NE） and citrullinated histone H3 （CitH3） in bone tissue were detected； the protein expressions of 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1） and 1α，25-dihydroxyvitamin D3-24-hydroxylase （CYP24A1） were also determined. RESULTS Compared with the normal group， the bone tissue of rats in the model group showed a significant reduction in the number of trabeculae， which was thinner broken and poorly connected， with significant destruction of the reticular structure， and an enlarged marrow cavity. Serum levels of NETs and RANKL， the protein expressions of MPO， NE， CitH3 and CYP24A1 in bone tissue were significantly increased or upregulated， while serum levels of E2， 25（OH）D3 and BGP as well as protein expressions of VDR and CYP27B1 were significantly decreased or downregulated （P＜0.05）. Compared with the model group， the histopathological changes in the bone tissue of rats in each administration group showed some degree of recovery， with significant improvements observed in most quantitative indicators （P＜0.05）. CONCLUSIONS Danggui buxue decoction can restore the E2 level in POF complicated with OP rats， and improve OP. The mechanism may be related to its ability to upregulate VD level and inhibit the formation of NETs.

Objective:To investigate the effects of multidisciplinary small-class teaching on expertise and skill acquisition and learning experience in standardized residency training in general surgery.Methods:Sixty residents of grade 2021 rotating in general surgery from January to August 2023 were divided into multidisciplinary teaching group ( n=30) and traditional teaching group ( n=30, to receive tradition one-on-one teaching). All the residents underwent a theoretical examination and Mini-Clinical Evaluation Exercise (Mini-CEX) skill assessment before admission, and the scores were compared between the two groups. At the end of training, the two groups were compared in terms of theoretical and Mini-CEX skill assessment scores and the degree of satisfaction with teaching. Statistical analysis was conducted using SPSS 26.0. Results:There were no significant differences in the theoretical assessment and Mini-CEX skill assessment scores before admission between the two groups ( P>0.05). At the end of training, the multidisciplinary teaching group had a significantly higher theoretical examination score [(88.15±3.45) vs. (72.25±4.36), P<0.05] and a significantly higher Mini-CEX score [(86.35±2.24) vs. (76.28±3.92), P<0.05] compared with the traditional teaching group. According to the survey, the residents in the multidisciplinary teaching group were more satisfied with teaching and more likely to recognize the teaching effects. Conclusions:Multidisciplinary small-class teaching can help improve the quality of standardized general surgery residency training on gastrointestinal tumor treatment, which is a highly accepted and effective attempt at standardized residency training.

Objective:To evaluate the effects of different intervention measures on duration of mechanical ventilation and the length of intensive care unit (ICU) stay in critically ill patients using network Meta-analysis.Methods:Randomized controlled trial (RCT) on the effects of different intervention measures on duration of mechanical ventilation and the length of ICU stay in critically ill patients were systematically searched in PubMed, Embase, China Biomedical Literature Database, CNKI, and other databases. The search time limit was from the establishment of the database to November 2023. Literature screening, quality assessment, and data extraction were independently conducted by two researchers. Network Meta-analysis was employed to assess the effects of each intervention on duration of mechanical ventilation and the length of ICU stay, and funnel plots were generated.Results:A total of 37 RCTs were included, involving 3?977 severe patients, 2?041 in the intervention group and 1?936 in the control group. Thirteen types of interventions were analyzed, including usual care (UC), early activity (EA), early comprehensive rehabilitation (ECR), early pulmonary rehabilitation (EPR), cluster intervention strategy (CS), sedation, analgesia and cluster nursing (SACN), music therapy (MT), neuromuscular electrical stimulation (NMES), modified education and visitation (MV), virtual reality (VR), auricular point sticking (APS), acupoint acupuncture (AA), and concerted intervention (COR). Network Meta-analysis showed that MV significantly better than COR [standardized mean difference ( SMD) = -2.35, 95% confidence interval (95% CI) was -4.30 to -0.39], EPR ( SMD = -2.59, 95% CI was -4.81 to -0.37), and UC ( SMD = -4.10, 95% CI was -5.71 to -2.49) in improving duration of mechanical ventilation in critically ill patients. COR was significantly better than UC in shortened length of ICU stay ( SMD = -5.72, 95% CI was -10.07 to -1.37). The efficacy ranking results showed that for duration of mechanical ventilation, the surface under the cumulative ranking curve (SUCRA) was highest for MV (85.4%) and EA (85.4%), followed by AA (74.9%), NMES (63.1%), ECR (51.7%), CS (48.8%), SACN (34.3%), COR (29.4%), EPR (26.1%), and UC (0.7%). For the length of ICU stay, COR had the highest SUCRA (82.3%), followed by APS (79.7%), MV (77.7%), EPR (68.0%), NMES (57.6%), CS (54.4%), ECR (51.1%), SACN (41.9%), MT (39.8%), EA (39.3%), AA (33.0%), VR (15.4%), and UC (9.8%). The funnel plot results of ICU stay showed that the publication bias between studies were relatively small. Conclusions:MV and COR appear to be effective interventions for reducing mechanical ventilation time and ICU stay in critically ill patients. However, due to the number and quality of included studies, these findings require confirmation through additional high-quality research.

Objective:To explore the cost-effectiveness and cost-benefit of chronic obstructive pulmonary disease (COPD) screening and intervention based on family doctor contract services.Methods:From January 2023 to October 2023, using purposive sampling and a cross-sectional survey method, 1 040 individuals aged 60 to 75 years who underwent physical examinations at community health service centers in Shanghai Minhang district were selected as research subjects. The subjects were divided into a control group ( n=532) and a study group ( n=508). The control group received conventional community health education and participated in a COPD screening and intervention program provided by the examination center. The study group received COPD screening and intervention provided by contracted family doctors under a tightly integrated medical consortium. The screening content for both groups included initial and follow-up risk assessment questionnaires, pulmonary function tests, bronchodilator tests, and CT scans. A comparative analysis was conducted on the screening compliance rate, positive rate, and cost-effectiveness and cost-benefit between the two groups. Results:A total of 251 individuals at high risk for COPD and confirmed COPD patients were identified through initial and re-screening in both groups, accounting for 24.13% of the subjects, including 222 individuals at high risk (21.35%) and 29 confirmed patients (2.79%). The study group had significantly higher compliance rates in questionnaire-based initial screening, questionnaire-based re-screening+pulmonary function tests, bronchodilator experiments, diagnosis, and subsequent CT scans than the control group ( χ2=33.563, 41.425, 24.842, 17.363, all P<0.05).There were significant higher proportions of high-risk individuals and patients identified through screening in the study group than those in the control group ( χ2=44.880, all P<0.05). The study group had significantly higher positive rates of questionnaire-based initial screening, pulmonary function tests, bronchodilator experiments, and CT scans than the control group ( χ2=29.191, 11.313, 12.370, 4.429, all P<0.05). The overall costs of the screening in the control and study groups were 36 100 and 53 900 yuan, respectively. The cost of pulmonary function tests in the screening for the control and study groups was 1.44 million and 2.45 million yuan, respectively, accounting for 43.19% of the total cost, which was the highest proportion among all costs. The per capita cost for identifying one high-risk individual or patient with COPD was 358.46 Yuan, and the cost in study groups was significantly lower than that in the control group (322.75 vs. 429.45 yuan, χ2=20.396, P<0.05). The per capita net benefits and cost-benefit ratios for the overall subjects in the two groups were 0.37 million yuan and 43.50, respectively. The average net benefit of the study group and the control group was 0.49 million yuan and 0.26 million yuan respectively. The average net benefit of the study group was 0.23 million yuan higher than that of the control group. The cost-benefit ratio of the study group and the control group were 46.77 and 38.61, respectively. The cost-benefit ratio of the study group was 8.16 higher than that of the control group. Conclusion:The screening and intervention for COPD based on family doctor contract services have significant effectiveness, with a marked improvement in screening compliance and high cost-effectiveness, and can be used in community medical institutions with relatively sound family doctor and medical consortium services for targeted COPD screening.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

BACKGROUND:At present,lumbar interbody fusion is widely used in the treatment of a variety of lumbar diseases.However,how to reduce postoperative complications such as pseudarthrosis formation,screw loosening and fracture,and cage failure remains a serious challenge. OBJECTIVE:To analyze the effect of total lumbar range of motion on the stress or strain of bone grafts,cage,and screw-rod system,so as to better guide patients to carry out lumbar activities to reduce the risks of pseudarthrosis formation and instrumentation failure. METHODS:An intact human L1-S1 finite element model was constructed using Mimics,3-Matic,HyperMesh,and Abaqus software and the transforaminal lumbar interbody fusion was simulated.The average strain of the interbody bone grafts and the peak stresses of the cage and screw-rod system were compared before and after applying the bending moment,and the changing trend with the total range of motion was analyzed.The stress nephogram was drawn to observe the stress distribution. RESULTS AND CONCLUSION:(1)Compared with applying the vertical compression load alone,the average strain of the interbody bone grafts,peak stresses of the cage and screw-rod system after applying bending moment increased by 2.6%-55.3%,65.6%-166.8%,and 36.0%-353.4%,respectively.(2)With the increase of total range of motion,the average strain of the interbody bone grafts increased nonlinearly and produced the maximum value under left and right axial rotation,while the peak stresses of the cage and screw-rod system increased linearly and produced the maximum value under left and right lateral bending.(3)The stress distribution of the interbody bone grafts and cage was related to the loading condition.The stress of the screw-rod system was mainly concentrated in the interfaces of the screw-bone and screw-rod.(4)Therefore,increasing axial rotation activity after operation may reduce the risk of pseudarthrosis formation,while reducing lateral bending activity may reduce the failure of the cage and screw-rod system.