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.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

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 study the application value of refined centralized management combined with scientific preventive maintenance in the standardized management of clinical ventilators.Methods:The ventilator failure information wad collected,a ventilator information management database was established,the refined and centralized management and scientific preventive maintenance measures for ventilators was developed in terms of planning,implementing,and updating the ventilator management system as well as training and assessment.119 ventilators in clinical use in People's Hospital of the Xinjiang Uygur Autonomous Region from 2021 to 2022 were selected,the conventional management mode(referred to as conventional mode,50 units)and the refined centralized management combined with scientific preventive maintenance mode(referred to as joint mode,69 units)were adopted respectively for management.The maintenance status of ventilators in the two modes and the total amount of work in 2021 and 2022 were compared.Results:There were 85 ventilator failures in 2021 and 58 ventilator failures in 2022 in conventional mode.34 ventilator failures in 2021 and 44 ventilator failures in 2022 in joint mode.The number of failures,maintenance time and satisfaction of clinical department with the ventilators of the joint mode in 2021 were(3.25±1.06)times/month,(12.57±10.31)days and(91.50±1.73)% respectively,the number of failures and maintenance time were less than those of conventional mode,satisfaction of clinical department was higher than that of the conventional mode,the difference was statistically significant(t=14.458,2.501,2.563,P<0.05).The number of failures of ventilators of joint mode in 2022 was(3.08±2.02)times/month,which was less than that of conventional mode,the difference was statistically significant(t=4.655,P<0.05).The number of failures,number of times to contact the equipment department,consumable costs,adverse events,and number of terminal disinfections for 119 ventilators of the two modes in 2021 were(10.25±2.34)times/month,(16.75±6.54)times/month,and CNY(44,000±49,300)/month,(2.49±0.92)pieces/month and(382.58±83.67)times/month,which were higher than those in 2022,the equipment completeness rate and frequency of clinical training were(88.27±1.29)% and(3.42±1.51)times/month,respectively,which were lower than those of 2022,the difference was statistically significant(t=5.124,6.103,4.099,7.884,1.980,5.607,3.564,P<0.05).Conclusion:Refined centralized management combined with scientific preventive maintenance can effectively reduce the number of ventilator failures,maintenance time and costs,etc.,and improve the quality of standardized management of clinical ventilators.

Objective:To investigate the application value of intraoperative motor nerve monitoring in cervical neurogenic tumor surgery.Methods:The efficacy of intraoperative neuromonitoring (IONM) was analyzed retrospectively in 18 patients, including 6 males and 12 females, aged from 15 to 74 years, treated in Affiliated Drum Tower Hospital, Medical School of Nanjing University from June 2019 to September 2022 who underwent total cystectomy of cervical neurogenic tumors under intraoperative nerve monitoring.Results:All 18 patients had complete tumor removal, including 8 patients with tumors from the vagus nerve and 10 patients with tumors from the brachial plexus nerve. Postoperative nerve functions were normal in patients with tumors from brachial plexus nerve, and incomplete vocal cord paralysis occurred in 2 patients with tumors from vagus vagus nerve. The total incidence of motor nerve injury was 11.1% (2/18). All patients were followed up for 6 to 45 months, with no tumor recurrence.Conclusion:Intraoperative neuromonitoring has significant values in surgery of cervical neurogenic tumors, which is helpful to remove completely the tumors on the basis of protecting the nerve functions to the maximum extent.

Telemedicine,particularly during the COVID-19 pandemic,has rapidly evolved and been widely adopted worldwide,notably enhancing epilepsy patient management.Literature review reveals effective remote consultations and treatments via phone,video,and apps by global healthcare professionals.Promising future directions include platforms for chronic epilepsy management,regional multicenter collaboration,extensive epilepsy database sharing,real-time patient monitoring,and online analytics.Despite its growth,telemedicine faces challenges such as the need for technological advances,regulatory improvements,and increased patient engagement to ensure both healthcare accessibility and quality are maintained.

Objective:To study the incidence and risk factors of early hyperglycemia in extremely preterm infants (EPIs).Methods:From January 2018 to December 2021, EPIs with gestational age (GA) <28 w born in our hospital and admitted to the neonatal department were retrospectively studied. According to the occurrence of early hyperglycemia (within 1 w after birth), the infants were assigned into hyperglycemia group and non-hyperglycemia group. Univariate and logistic regression were used to analyze the risk factors of early hyperglycemia in EPIs.Results:A total of 218 cases of EPIs were enrolled, including 70 (32.1%) in the hyperglycemia group and 148 (67.9%) in the non-hyperglycemia group. The incidence of early hyperglycemia in EPIs with GA<25 w was 10/20 and 11/16 in EPIs with birth weight (BW) ≤700 g. The GA and BW of the hyperglycemia group were significantly lower than the non-hyperglycemia group ( P<0.05). More infants in the hyperglycemia group had 1-min and 5-min Apgar≤7 than the non-hyperglycemia group ( P<0.05). Logistic regression analysis showed that increased BW ( OR=0.995, 95% CI 0.993~0.997, P<0.05) was a protective factor for early hyperglycemia in EPIs, while male gender ( OR=2.512,95% CI 1.232~5.123, P<0.05), vasoactive drug use during the first week of life ( OR=2.687, 95% CI 1.126~6.414, P<0.05), maternal hypertension during pregnancy ( OR=14.735, 95% CI 1.578~137.585, P<0.05) were risk factors for early hyperglycaemia in EPIs. Conclusions:Early hyperglycemia are common among EPIs. Low BW, male gender, vasoactive drug use during the first week of life and maternal hypertension during pregnancy may increase the risk of early hyperglycemia.

Objective:To analyze the current situation of researches on the fear of disease progression at home and abroad, and sort out the research hotspots and development context.Methods:The relevant literature about fear of disease progression published by China National Knowledge Infrastructure (CNKI) and Web of Science core collection database were systematiclly searched, and the search period was from January 1, 2002 to June 24, 2022. CiteSpace 5.8.R3 software was used for visual analysis of relevant literature.Results:A total of 340 articles were retrieved from CNKI and 1 199 articles were retrieved from Web of Science core collection database. The countries and institutions with the highest number of international publications were Germany, Technical University of Munich and The University of Sydney, with close cooperation among authors and poor inter-institutional cooperation. Domestic research focused on the influencing factors of fear of disease progression and its relationship with depression, anxiety, social support and quality of life, while foreign research focused on breast cancer and its survivors, depression, anxiety, quality of life, reliability and validity of the questionnaire and the feasibility of intervention.Conclusions:The number of articles published at home and abroad is generally on the rise. Compared with foreign countries, there is still a certain gap in the research on fear of progression in China. In the future, China should timely pay attention to the development trends and hot frontiers in this field internationally, so as to promote the research and development of fear of disease progression in China.

Objective:To retrieve and summarize evidence on non-pharmacological sleep management in adult critically ill patients, providing reference for sleep intervention by ICU medical and nursing staff.Methods:The literature on non-pharmacological sleep management in adult critically ill patients was systematically searched in domestic and foreign databases and guideline websites. The search period was from the establishment of the database to February 2023. After screening the literature based on inclusion and exclusion criteria, two evidence-based trained researchers independently evaluated the quality of the included literature, extracted and summarized evidence.Results:A total of 13 articles were included, including 3 clinical guidelines, 9 systematic reviews, and 1 randomized controlled trial. A total of 21 best pieces of evidence were summarized, covering 5 aspects, including strengthening nurse education and training, improving ward environment, reducing sleep interruption, selecting mechanical ventilation modes reasonably, and promoting physical and mental relaxation.Conclusions:The evidence summarized can provide reference for the development of non-pharmacological sleep management plans for adult critically ill patients. ICU medical and nursing staff should carefully apply evidence in clinical practice based on evidence, fully consider the human resources and actual situation of the department, and combine it with the needs of patients.