N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

BACKGROUND:The more vertical the femoral neck fracture line,the more shear force the femoral neck fracture may bear,so it may be prone to internal fixation failure,nonunion,or necrosis of the femoral head.At present,there is controversy as to which hollow nail fixation mode is ideal. OBJECTIVE:To evaluate different configurations and numbers of cannulated screw configurations to learn more about the biomechanical differences in vertical fractures of the femoral neck using finite element analysis. METHODS:Femoral CT data were collected from a 24-year-old healthy male volunteer and imported into Mimics software to build a three-dimensional geometric model of the femur.Model refinement and surface fitting processing were carried out in Geomagic software and imported into SolidWorks software to establish a vertical fracture model of the femoral neck.Six cannulated screw models were established,including three triangle configuration,three inverted triangle configuration,three double-plane double-support configuration(F scheme),three transverse configuration,four diamond configuration and four Alpha configuration.The peak stress,strain and displacement of internal fixation and femoral fracture models under different loads(350,700,1 400,and 2 100 N)were compared among different configurations. RESULTS AND CONCLUSION:(1)Under four kinds of loads,screw stress conditions were as follows:biplanar double-supported configuration(F scheme)>transverse configuration>inverted triangle configuration>positive triangular configuration>Alpha configuration>rhombus configuration.The peak value of Von mises stress was concentrated in the screw close to the fracture line.(2)Under four kinds of loads,the screw displacement was Alpha configuration>inverted triangle configuration>positive triangular configuration>biplanar double-supported configuration(F scheme)>rhombus configuration>transverse configuration,and the peak displacement was mainly concentrated on the hollow screw head.(3)Under four kinds of loads,the stress conditions of the proximal femoral bone block were biplanar double-supported configuration(F scheme)>transverse configuration>inverted triangle configuration>Alpha configuration>positive triangular configuration>rhombus configuration,and the stress peak mainly concentrated in the lower neck of femur.(4)Under 350 N load,the displacement of the proximal femur bone block was transverse configuration>biplanar double-supported configuration(F scheme)>positive triangular configuration>Alpha configuration>inverted triangle configuration>rhombus configuration.In the other three loads,the peak displacement of the inverted triangle configuration was smaller than that of the rhombus configuration.The peak displacement was mainly concentrated in the head.(5)The rhombus configuration was the most dispersed in the stress distribution of the proximal femoral bone.The rhombus configuration was the smallest in the peak displacement of the femur.The stress,displacement and peak displacement of the fracture end of each internal fixed model increased gradually with the increase of load.(6)The biomechanical performance of the four diamond-shaped models in the internal fixation of vertical femoral neck fractures is better than that of other groups of models.The four rhomboid models have stable fixation,small displacement value of fracture end and dispersed stress,which can help resist shear force and prevent varus collapse and create a good mechanical environment for fracture healing.

Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.

Objective: To analyze the application of digital games for interventions to reduce risky sexual behavior among adolescents, so as to provide a reference for reducing adolescent risky sexual behavior. Methods: The study used PubMed, Web of Science, Cochrane Library, Scopus, Embase, China Biomedical Database, CNKI, Wanfang Database and VIP to carry out a literature search of the application of digital games for interventions aimed at reducing risky sexual behavior among adolescents covering the time period up until February 2024. Results: A total of 10 English articles were included, involving a total of 3 063 adolescents aged 10-24 years old. The publication time spanned from 2013 to 2023. The development and design of the digital games were mostly based on cognitive behavior theory and authentic decision making situations and dialogues. The game participants were divided into single party and multi party categories, mainly using virtual role playing, interactive narrative, and adventure challenges, and there were some differences in content. Digital game intervention had good feasibility and acceptability, which could improve adolescents sexual health knowledge, attitudes, self efficacy, and risk perception, so as to reduce the occurrence of risky behavior. Conclusion As an intervention aimed at reducing risky sexual behavior in adolescents, digital show has significant advantages and can serve as a new prevention and control strategy.

Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.

Objective:To assess the efficiency of modified enrichment method for cell-free fetal DNA (cffDNA) through purified superparamagnetic beads during non-invasive prenatal testing (NIPT).Methods:A total of 26 252 pregnant women undergoing NIPT at the Maternal and Child Health Care Hospital of Haidian District from December 2017 to September 2022 were recruited and randomly assigned into the conventional group ( n = 10 573) and the modified enrichment group ( n = 15 679), who were then subjected to the screening and enrichment of the cffDNA using a conventional and modified technique, respectively. High-risk pregnant women detected by NIPT were subjected to invasive prenatal diagnosis. All women were followed up for their pregnancy outcomes, and the detection efficacy of the two methods was compared in terms of fragment size, concentration of cffDNA, duplicate detection rate, and indices of clinical laboratory tests. Results:The fragment size of the main peak of the cell-free DNA library of the modified enrichment group was significantly lower than that of the conventional group [267 (264, 269) bp vs. 294 (292, 296) bp, P<0.01], while the concentration of cffDNA was significantly higher [21.86% (17.61%, 26.36%) vs. 9.08% (6.87%, 11.87%), P<0.01]. In addition, the duplicate detection rate (0.740% vs. 2.02%, χ2=83.90, P<0.01) and detection failure rate (0.006% vs. 0.057%, P<0.05) in the modified enrichment group were significantly lower than those of the conventional group. The combined positive predictive value (PPV) in both high-risk (64.3% vs. 76.1%) and low-risk (35.3% vs. 45.5%) pregnant women from the modified enrichment group was slightly lower than those from the conventional group, though no significant difference was detected. There was one false negative case for trisomy 21 among the high-risk pregnant women from the conventional group, and no false negative case was found in the modified enrichment group. Conclusion:The modified technique to screen and enrich the cffDNA has significantly enhanced the relative concentration of cffDNA and reduced the failure and duplication detection rate of NIPT, which has significantly reduced the incidence of false negative cases due to the low concentration of cffDNA, and greatly increased the overall detection efficacy of NIPT.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.