BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

OBJECTIVE To explore the mechanism by which Cuscuta chinensis flavonoids （CCF） promote decidualization and improve recurrent spontaneous abortion （RSA）. METHODS HTR-8/SVneo cells in logarithmic growth phase were randomly divided into blank group， lipopolysaccharide （LPS） group， CCF group， SGK2 inhibitor （GSK650394， abbreviated as “GSK”） group and CCF+GSK group. Each group was treated with the corresponding agents accordingly. HTR-8/SVneo cells with SGK2 knockdown were randomly divided into small interfering RNA of SGK2 （siSGK2） group and siSGK2+CCF group； additionally， blank group and LPS group were established； each group was treated with the corresponding agents accordingly. The cell survival rate， expression levels of WNK signaling pathway- and decidualization-related proteins and mRNAs， as well as mitochondrial membrane potential levels， were assessed in each group before and after SGK2 knockdown. RSA mice model was constructed and randomly divided into model group， CCF low-dose group， CCF high-dose group， GSK group， and combined dosing group， with 4 mice in each group. Other 4 normal pregnant female mice were selected as the control group. The number of implanted embryos， viable fetuses， and lost embryos in mice was recorded. The morphological changes of endometrium and decidualization were observed， and WNK signaling pathway- and decidualization-related proteins and mRNAs expressing levels as well as mitochondrial membrane potential levels were all detected. RESULTS Compared with the blank group， the cell survival rate， as well as the protein and mRNA expression levels of SGK2， WNK1， WNK4， prolactin， insulin-like growth factor- binding protein-1， oxidative stress responsive kinase 1， and Ste20-like proline-/alanine-rich kinase were significantly reduced in the LPS group （P＜0.05）； compared with the LPS group， the cell survival rate and the expression levels of the above- mentioned proteins and mRNAs were significantly increased in the CCF group， while the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly decreased in the GSK group （P＜0.05）； compared with the CCF group， the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the CCF+GSK group （P＜0.05）. After knocking down SGK2， compared with the LPS group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the siSGK2 group （P＜0.05）； compared with the siSGK2 group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly increased in the siSGK2+CCF group （P＜0.05）. The in vivo experimental results showed that CCF treatment can significantly improve the number of implanted embryos and viable fetuses in RSA model mice and reduce lost embryos， the expression levels of the above-mentioned proteins and mRNAs in endometrial tissue were significantly increased， and the red/green fluorescence intensity ratio was significantly increased （P＜ 0.05）； the combined dosing group could reverse the effect of CCF （P＜0.05）. CONCLUSIONS CCF can activate SGK2， up- regulate the WNK signaling pathway， promote endometrial decidualization， and improve RSA.

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.

Objective To explore the longitudinal trajectories of symptom clusters in patients with rectal cancer within 6 months after laparoscopic anal preservation surgery,and analyze the predictive factors of each trajectory subgroup.Methods A longitudinal survey was conducted to select 128 patients who underwent laparoscopic anal preservation surgery for rectal cancer at the Department of Gastrointestinal Surgery,a tertiary hospital in Nanchong from November 2021 to April 2022.The general information questionnaire,Chinese version of Anderson Symptom Inventory for Gastrointestinal Cancer and Charlson Comorbidity Index were used to conduct follow-up surveys of the selected patients at 2 weeks,1 month,3 months and 6 months after surgeiy.The symptom cluster were extracted by exploratory factor analysis,and the latent category growth model was constructed to identify the trajectory subgroups of each symptom cluster.The predictive factors of each trajectory subgroup were analyzed by Mplus statistical software.Results There were 4 symptom clusters within 6 months after laparoscopic anus preserving surgeiy for rectal cancer,which were named as sickness symptom cluster,psychological-sleep symptom cluster,gastrointestinal symptom cluster,and psychological-treatment-related symptom cluster.The variance contribution rates were 65.173％,66.225％,62.421％,and 60.492％,respectively.The latent class growth model identified that there are 4 to 5 trajectory subgroups in the symptom cluster.Gender,education level,Charles Comorbidity Index,clinical T stage,medical cost burden,and treatment method were the predictors of high-risk trajectory subgroups in the symptom cluster(P＜0.05).Conclusion There are 4 symptom clusters within 6 months after laparoscopic anus preserving surgeiy for rectal cancer.The gastrointestinal symptom cluster is a specific symptom cluster for this type of patients with the heaviest symptom burden.The overall trajectory of each symptom cluster shows a dynamic decline trend,but individual trajectoiy subgroups still have an exacerbation trend.There are differences in predictive factors for different symptom clusters.Clinical medical staff should pay attention to the management of symptom clusters in patients with female patients,low education level,high Charles Comorbidity Index,high clinical T stage,heavy medical cost burden,and patients whose treatment method is chemotherapy plus surgery.High-risk groups should be timely identified;corresponding intervention methods were dynamically adjusted;the quality of precision nursing was improved.

Objective To investigate the best evidence application of exercise prescription in patients with chronic heart failure in clinical practice and evaluate its effectiveness.Methods The best evidence of exercise prescription for patients with chronic heart failure was summarized,and the evidence-based practice plan was developed,and it was implemented in the cardiology department of a tertiary hospital in Zhejiang Province from August to October,2022.Nurses'exercise prescription knowledge-attitude-practice level,implementation rate of review indicators,the length of hospital stay,exercise endurance,daily living ability and grip strength of both groups before and after the intervention were compared.Results After the application of the best evidence,the score of knowledge dimension was(9.34±0.98)points;the score of attitude dimension was(63.29±1.37)points;the score of practice dimension was(25.49±1.51)points,which were statistically significant compared with the scores before the application of evidence(P<0.05).After the application of the best evidence,the implementation rate of 16 review indicators was higher than that before the application of evidence(P<0.001).The length of hospital stay in the evidence application group was shorter than that in the baseline examination group(Z=-2.610,P<0.001).After intervention,the exercise endurance,daily living ability and grip strength of patients in the evidence application group were improved compared with the baseline review group,and the difference was statistically significant(P<0.05).Conclusion After the application of the best evidence of exercise prescription in patients with chronic heart failure,it can improve the level of knowledge,attitude and practice of nurses on exercise prescription,standardize the compliance of nurses'exercise prescription,reduce the number of days in the hospital,and improve patients'exercise endurance,daily living ability and grip strength.

Objective:To identify the differentially expressed proteins that caused hippocampal damage after liver ischemia-reperfusion (I/R) in rats.Methods:Eighteen clean-grade healthy juvenile male Sprague-Dawley rats, aged 2 weeks, weighing 20-30 g, were divided into 2 groups ( n=9 each) using a random number table method: sham operation group (S group) and liver I/R group (IR group). A rat model of liver I/R injury was prepared by restoring perfusion after 1 h of liver ischemia. The rats were sacrificed after being anesthetized at day 3 of reperfusion, and the hippocampal tissue was isolated and analyzed to obtain gene expression profiles. Differentially expressed genes were identified using the R software, and further protein interaction networks were constructed through Cytoscape and Kyoto Encyclopedia Genes and Genomes pathway analysis to determine the differentially expressed proteins. Quantitative real-time polymerase chain reaction and Western blot were used for validation. Results:A total of 45 differentially expressed proteins were identified by the proteomic analysis of hippocampal tissues, including 36 significantly up-regulated proteins and 9 significantly down-regulated proteins. The proteins with significant expression related to injury were identified from the PPI network complex using the CytoHubBA plug-in cystscape: Ras-related C3 botulinum toxin substrate (RAC2), HRAS, phosphatidylinositol-3-kinase inhibitor phosphatase and tensin homologue (PTEN), and N-methyl-D-aspartate ionotropic glutamate receptor 2b (GRIN2b). The results of quantitative real-time polymerase chain reaction and Western blot showed that the expression of RAC2, HRAS, PTEN, and GRIN2b in the hippocampal tissue was significantly up-regulated in IR group compared with S group ( P<0.05). The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that differentially expressed proteins were significantly enriched in the expression of PD-L1 and its checkpoint pathway, long-term potentiation, and regulation of the Wnt signaling pathway in cancer. Conclusions:The mechanism by which liver I/R induces hippocampal injury may be related to the up-regulation of the expression of RAC2, HRAS, PTEN and GRIN2b in rats.

Objective:To explore the effect of esketamine on inflammatory cytokines and myocardial injury markers in children undergoing living-donor liver transplantation (LT).Methods:Considering the inclusion criteria, 50 children with biliary atresia were selected for living donor LT. They were equally randomized into two groups of control (C) and esketamine (E) (25 cases each). Esketamine 0.5 mg/kg was administered to group E during induction and continued at a dose of 0.5 mg·kg –1·h -1 after an induction of anesthesia. Group C provided the same dose of 0.9% sodium chloride injection during induction and then continued to pumping until the end of the procedure. Basic profiles of two groups were recorded. Hemodynamic parameters, such as heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP), were monitored at 5 min of anesthesia induction (T 0), 30 min of anhepatic phase (T 1), immediately after repercussion (T 2), 30 min of neohepatic phase (T 3) and end of surgery (T 4) in both groups. Central venous blood samples were collected at T 0, T 1, T 3 and T 4. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB) ,tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured. The incidence of adverse cardiac events, postoperative mechanical ventilation time, ICU stay and hospitalization length were compared. Results:As compared with T 0, mean arterial pressure (MAP) at T 2 declined markedly in group E [(48.6±12.7) mmHg (1 mmHg=0.133 kPa) vs (55.6±10.7) mmHg, P<0.001] and C [(39.3±8.0) mmHg vs (53.2±9.4) mmHg, P<0.001 ] ;As compared with T 0, the TNF-α and IL-6 spiked at T 3 in group C [169.0 (207.1) ng/L vs 43.8 (26.4) ng/L, (132.63±51.75) ng/L vs (51.79±17.83) ng/L, P<0.001] and E [78.5 (138.8) ng/L vs 43.8 (26.4) ng/L, (87.44±32.17) ng/L vs (51.79±17.83) ng/L, P<0.001 ] ; In group C, the concentration of myocardial injury markers CK-MB and cTnI rose at T 3/T 4 compared with T 0[T 3 vs T 0: 5.7 (5.4) μg/L vs 4.0 (3.5) μg/L, 0.09 (0.08) μg/L vs 0.02 (0.02) μg/L; T 4 vs T 0: 5.3 (5.0) μg/L vs 4.0 (3.5) μg/L, 0.07 (0.08) μg/L vs 0.02 (0.02) μg/L, P<0.001 ]. In group E, the levels of CK-MB and cTnI were higher at T 3/T 4 than those at T 0[T 3 vs T 0: 7.0 (5.0) μg/L vs 4.6 (2.1) μg/L, 0.06 (0.09) μg/L vs 0.03 (0.04) μg/L; T 4 vs T 0: 5.4 (4.9) μg/L vs 4.6 (2.1) μg/L, 0.03 (0.06) μg/L vs 0.03 (0.04) μg/L; P<0.001]. Compared with group C, the MAP of E rose at T 1/T 2/T 3 [(58.8±10.3) mmHg vs (53.3±8.6) mmHg, P=0.048; (48.6±12.7) mmHg vs (39.3± 8.0) mmHg, P=0.003; (55.8±7.4) mmHg vs (51.5±7.3) mmHg, P=0.044]. Compared with group C, TNF-α and IL-6 decreased in E at T 3/T 4[T 3: 78.5 (138.8) ng/L vs 169.0 (207.1) ng/L, P=0.010; (87.44±32.17) ng/L vs (132.63±51.75) ng/L, P=0.017. T 4: 62.3 (118.3) ng/L vs 141.3 (129.2) ng/L, P=0.001; (74.34±26.38) ng/L vs (100.59±30.40) ng/L, P=0.002]. Compared with group C, cTnI decreased in E at T 3/T 4[0.06 (0.09) μg/L vs 0.09 (0.08) μg/L, P=0.014; 0.03 (0.06) μg/L vs 0.07 (0.08) μg/L, P=0.003]. Compared with group C, the mechanical ventilation time in group E decreased [195 (120) min vs 315 (239) min, P<0.001]. Compared with group C, the incidence of severe hypotension [16%(4/25) vs 48% (12/25), P=0.015 ], bradycardia [12% (3/25) vs 36 % (9/25), P=0.047 ], myocardial ischemia [4 % (1 /25) vs 24 % (6/25), P=0.042 ] and premature ventricular contractions [0 vs 4 %(1/25), P=0.312 ] decreased in group E. Conclusion:Intraoperative dosing of esketamine may suppress inflammatory reactions and alleviate perioperative myocardial injury in children undergoing living-donor LT.

Objective:To analyze the research hotspots and trends in the field of emergency nursing safety management at home and abroad through bibliometrics, and to provide reference for the research and clinical practice of emergency nursing safety management in China.Methods:The relevant literature in the field of emergency nursing safety management in China National Knowledge Infrastructure and Web of Science databases were searched from January 1, 2014 to December 31, 2023. CiteSpace6.2.R7 software was used for keyword co-occurrence, clustering and mutation analysis, and the hotspot and development trend of the literature were analyzed.Results:A total of 883 literatures were included, including 665 Chinese literatures and 218 English literatures.Nursing safety management had attracted much attention in China, but there were few high-level studies.And the foreign related research had steadily increased. The content of foreign literature was different from that of domestic literature. Chinese literature focused on nursing risk, nursing quality, nursing management, application effectiveness, emergency triage, etc, and focused on critically ill patients.The English literature mainly focused on medical errors, risk management, organizational culture, maternal investment, emergency department, training, depression, emergency care systems,improvement, etc.Conclusions:The research on emergency nursing safety management in China is still in the initial stage. In the future, it is necessary to strengthen safety culture construction, adverse event management, emergency observation, establishment of safety management measures, drug safety management strategies, and patient satisfaction, etc.

Objective:To assess the performance of machine learning(ML),and integrate the clinical parameters with coronary artery calcium(CAC)score of computed tomography(CT)and quantification of automated epicardial adipose tissue(EAT),so as to predict the long-term risk of myocardial infarction(MI)and cardiogenic death in asymptomatic patients.Methods:A total of 1 058 subjects with cardiovascular risk factors and without symptoms of coronary heart disease who underwent physical examination at the Fifth Medical Center of Chinese PLA General Hospital from January 2013 to October 2015 were selected as this study subjects.A long-term follow-up was conducted on them after CAC score.EAT volume and density were quantified using a fully automated deep learning method.ML extreme gradient boosting was trained by using clinical data,risk score of atherosclerotic cardiovascular disease,CAC score and automated EAT measure,and the repeated 10-fold cross validation was used to verify the model.Results:During the 8-year follow-up period,61 cases of 1 058 subjects occurred events of MI and(or)cardiac death.The area under curve(AUC)value of ML was significantly higher than that of the atherosclerotic cardiovascular disease(ASCVD)risk and the predicting events of CAC score(ML:0.82,ASCVD:0.77,CAC:0.77).Compared with ML with only clinical variable,machine learning based on ASCVD,CAC and EAT had more predictive ability for MI and cardiac death[AUC 0.82(95%CI:77-87)vs.0.78(95%CI:0.72-0.84),P=0.02].The survival rate of subjects with high ML scores had a greater decline degree with the increasing of time,therefore,the subjects with higher ML scores were more likely to experience events.Conclusion:ML,which integrated clinical and quantitative imaging variables,can provide long-term risk prediction for patients with cardiovascular risk factors.