BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

Objective To construct a module for drug-induced central nervous system adverse reactions(CNS-ADR)within the Clinical Adverse Drug Event Active Monitoring and Intelligent Assessment Alert System-Ⅱ(ADE-ASAS-Ⅱ),and to conduct a large-scale,real-world active monitoring and evaluation of CNS-ADR specifically related to imipenem/cilastatin.Methods Based on literature review,spontaneous report evaluation,and initial word set of CNS-ADR related descriptions in electronic medical records,text recognition technology was used to construct and optimize the condition settings of the CNS-ADR automatic monitoring module.Hospitalized patients using imipenem/cilastatin were retrospectively monitored from 2017 to 2021,and the positive patients which had CNS-ADR were statistically described in terms of the demographic characteristics,CNS symptoms,and hospital departments.Results Based on a repeated testing optimization using 1 185 manually monitored results,the best setting for the determined module includes 62 sets of keywords,with a positive predictive value(PPV)of 13.63％and a recall rate of 100％.Expanding the monitoring to 8 222 medication users using this module,281 cases of positive causality were identified,with an incidence rate of 3.42％.Among them,patients over 60 years old accounted for 50.17％,and the main manifestations of CNS-ADR were epileptic seizures,headaches,mania,and delirium.Conclusion The CNS-ADR automatic monitoring module established based on ADE-ASAS-Ⅱ provides fast and reliable text data mining support for conducting real-world research on CNS-ADR.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.

Objective:To evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Background With the increasing aging population in China, there is a significant shortage of labor force. Delaying retirement age has become a potential method to alleviate this labor shortage. Objective To estimate the healthy working life expectancy (HWLE) of individuals aged 50 years old in China. Methods This study was based on data from four waves (2011—2018) of the China Health and Retirement Longitudinal Study (CHARLS). HWLE was estimated for the overall sample of individuals aged 50 years old and above and stratified by sex, educational attainment, marital status, occupation, Hukou type, and region by using continuous-time multistate modelling. Results A total of 50991 person-times aged ≥ 50 years and older were included in the study. The average total life expectancy of the Chinese population aged 50 years old was 29.72 years (95%CI: 29.28, 30.12 years), with a HWLE of 14.05 years (95%CI: 13.76, 14.33 years). The remaining years lived in the states of healthy but not working, not healthy but working, and not healthy and not working were 8.82 years (95%CI: 8.53, 9.15 years), 2.54 years (95%CI: 2.41, 2.68 years),and 4.30 years (95%CI: 4.08, 4.54 years), respectively. The HWLE (95%CI) of individuals in the baseline states of healthy and working, healthy but not working, not healthy but working, and not healthy and not working were 14.97 (14.69, 15.23), 10.86 (10.52, 11.22), 11.73 (11.31, 12.09), and 9.51 (9.09, 9.97) years, respectively. Additionally, women had a higher total life expectancy (95%CI) than men [31.84 (31.10, 32.54) years vs 27.98 (27.35, 28.50) years], but a lower HWLE than men [12.47 (12.12, 12.82) years vs 15.62 (15.23, 15.98) years]. There was no difference in total life expectancy between rural residents and urban residents [29.43 (28.88, 29.97) years vs 30.31 (29.47, 31.02) years], but rural residents had a higher HWLE than urban residents [15.74 (15.39, 16.10) years vs 11.38 (10.97, 11.73) years]. Residents in East China [14.66 (14.22, 15.06) years] and Central China [14.15 (13.86, 14.43) years] had a higher HWLE than residents in West China [13.61 (13.27, 13.98) years] and Northeast China [13.06 (12.51, 13.63) years]. Conclusion The HWLE of Chinese residents supports the policy of raising the retirement age. There are differences in HWLE levels between urban and rural areas, as well as across different regions. Providing more flexible employment opportunities for older adults can help mitigate the labor shortages caused by population aging.