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 explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective To analyze the etiological characteristics of children with pneumonia and provide a reference for regional pneumonia prevention and control.Methods A retrospective analysis was conducted on the clinical data of 864 children with pneumonia admitted to this hospital from January to December 2023.The disease types,common pathogen infections,and drug-resistant Mycoplasma pneumoniae infections in dif-ferent age groups were analyzed.Results Among the 864 children with pneumonia,there were 466 cases(53.94%)of bronchopneumonia,290 cases(33.56%)of asthmatic bronchopneumonia,and 108 cases(12.50%)of lobar pneumonia.The infections were caused by Mycoplasma pneumoniae in 470 cases(54.40%),Haemophilus influenzae in 196 cases(22.69%),Streptococcus pneumoniae in 172 cases(19.91%),Moraxella catarrhalis in 143 cases(16.55%),Staphylococcus aureus in 142 cases(16.43%),Re-spiratory syncytial virus in 54 cases(6.25%).The drug resistance rate of Mycoplasma pneumoniae was 20.00%(94/470),and that of Staphylococcus aureus was 7.75%(11/142).Among 864 children with pneumo-nia,there was 1 case(0.12%)of drug-resistant of Mycoplasma pneumoniae infection in the 0-<1 year age group,29 cases(3.36%)in the 1-<4 years age group,39 cases(4.51%)in the 4-<7 years age group,21 cases(2.43%)in the 7-<10 years age group,and 4 cases(0.46%)in the 10-<15 years age group.Conclu-sion Mycoplasma pneumoniae is the main pathogen in children with pneumonia,and its drug resistance rate is relatively high.

The purpose of this survey was to understand the occurrence of hypocalcemia in dairy cows in large-scale pasture and its relationship with production performance,disease and culling.Eighty-one large-scale pastures were selected in China to carry out a questionnaire survey on the lactation performance,reproductive performance,disease status and culling situations of dairy cows,and analyzed the production data of dairy farms by SPSS software.The survey results show that the incidence of hypocalcemia in dairy cows in pasture was different,the subclinical type was nearly twice as high as the clinical type,and the incidence rate of hypocalcemia was higher in about 30％of pasture.Hypocalcemia has no obvious effect on the lactation performance of dairy cows on dairy farms.However,a high incidence rate can reduce the conception rate,increase the incidence of subclinical mastitis,ketosis,and other common internal diseases,and raise the annual culling rate and culling rate of adult cows.Clinical,subclinical and total incidence of hypocalcemia have differ-ent effects on reproduction and diseases such as mastitis and ketosis,but clinical hypocalcemia is more harmful.Hypocalcemia is still an important metabolic disease that harms the health and pro-duction of dairy cows in large-scale pastures in China.For farms with a high incidence rate,it is recommended to conduct regular monitoring of blood calcium levels in dairy cows before and after calving,and to conduct in-depth investigations into the related pathogenic factors.This will provide a scientific basis for improving the prevention measures for hypocalcemia,reducing the incidence of the disease,increasing reproductive efficiency,and reducing culling rates.

The purpose of this survey was to understand the occurrence of hypocalcemia in dairy cows in large-scale pasture and its relationship with production performance,disease and culling.Eighty-one large-scale pastures were selected in China to carry out a questionnaire survey on the lactation performance,reproductive performance,disease status and culling situations of dairy cows,and analyzed the production data of dairy farms by SPSS software.The survey results show that the incidence of hypocalcemia in dairy cows in pasture was different,the subclinical type was nearly twice as high as the clinical type,and the incidence rate of hypocalcemia was higher in about 30％of pasture.Hypocalcemia has no obvious effect on the lactation performance of dairy cows on dairy farms.However,a high incidence rate can reduce the conception rate,increase the incidence of subclinical mastitis,ketosis,and other common internal diseases,and raise the annual culling rate and culling rate of adult cows.Clinical,subclinical and total incidence of hypocalcemia have differ-ent effects on reproduction and diseases such as mastitis and ketosis,but clinical hypocalcemia is more harmful.Hypocalcemia is still an important metabolic disease that harms the health and pro-duction of dairy cows in large-scale pastures in China.For farms with a high incidence rate,it is recommended to conduct regular monitoring of blood calcium levels in dairy cows before and after calving,and to conduct in-depth investigations into the related pathogenic factors.This will provide a scientific basis for improving the prevention measures for hypocalcemia,reducing the incidence of the disease,increasing reproductive efficiency,and reducing culling rates.

Objective To investigate the risk factors and preventive strategies of pancreaticoduodenectomy postoperative hemorrhage.Methods A total of 208 patients who underwent pancreaticoduodenectomy in the Department of Hepatobiliary Surgery of the 904th Hospital of Joint Logistics Support Force,PLA from January 2017 to December 2021 were enrolled.Twenty-one patients with postoperative hemorrhage were retrospectively analyzed.Results Univariate analysis indicated that postoperative hemorrhage was mainly associated with pancreatic leakage,biliary leakage,abdominal infection,hypoproteinemia,diabetes,improper use of ultrasound knife,skeletonization,intraoperative blood loss,preoperative jaundice,etc.(P<0.05),but not gender and age(P>0.05).Among the 21 patients with postoperative hemorrhage,4 cases recovered after conservative treatment such as hemostasis and blood transfusion,6 cases underwent interventional treatment,11 cases underwent abdominal exploration,and 2 cases died of postoperative multiple organ failure.Pancreatic leakage(OR=3.963,95%CI:1.120-14.025),biliary leakage(OR=4.013,95%CI:1.173-13.734)and abdominal infection(OR=7.545,95%CI:1.833-31.051)were independent risk factors for postoperative hemorrhage.Conclusions The improvement of anastomotic manipulation,reduction of anastomotic leakage,and control and prevention of abdominal infection are important to prevent postoperative hemorrhage of pancreaticoduodenectomy.Surgical treatment should be performed as soon as possible for the patients with poor conservative treatment effect.

Objective To investigate the relationship between serum chemokine C-X-C-motif ligand 16(CXCL16),CC chemokine ligand 20(CCL20)and inflammatory factors and mucosal healing in patients with ulcerative colitis(UC).Methods A total of 170 UC patients admitted to Chengdu Shuangliu District First People's Hospital/West China Airport Hospital of Sichuan University from January 2021 to October 2022 were selected as the study group,and 100 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.The levels of serum CXCL16,CCL20 and inflamma-tory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-17(IL-17),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in the two groups were compared.The correlation between serum CX-CL16,CCL20 and inflammatory factors in UC patients was analyzed.According to the prognosis of mucosal healing after treatment,UC patients were divided into good healing group and poor healing group.Serum CX-CL16 and CCL20 levels of patients with different prognosis were compared.Univariate and multivariate Logis-tic regression analysis models were used to analyze the risk factors of poor mucosal healing in UC patients af-ter treatment,and the predictive value of serum CXCL16 and CCL20 in poor mucosal healing in UC patients after treatment was analyzed by receiver operating characteristic(ROC)curve.Results The levels of serum CXCL16,CCL20,IL-1β,IL-6,TNF-α,IL-17 and CRP in the study group were significantly higher than those in the control group,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum CX-CL16 and CCL20 were positively correlated with IL-1β,IL-6,TNF-α,IL-17 and CRP in UC patients,respec-tively(P＜0.05),and serum CXCL16 was positively correlated with CCL20(P＜0.05).The levels of CX-CL16 and CCL20 in poor healing group were significantly higher than those in good healing group,and the difference was statistically significant(P＜0.05).Multifactor Logistic regression analysis showed that in-creased CXCL16 level,CCL20 level,drinking history,severity of disease classification,erythrocyte sedimenta-tion rate(ESR)level and CRP level were risk factors for poor mucosal healing in UC patients after treatment(P＜0.05).ROC curve results showed that the combined detection of serum CXCL16 and CCL20 predicted a larger area under the curve(AUC)for poor mucosal healing after treatment in UC patients,and the combined detection of serum CXCL16 and CCL20 with ESR and CRP predicted the largest AUC for poor mucosal heal-ing after treatment in UC patients.Conclusion The serum levels of CXCL16 and CCL20 in UC patients are closely related to inflammatory factors,and the combined detection have high predictive value for poor muco-sal healing in UC patients after treatment.

Abrin,the most lethal plant-derived toxin known today,has attracted widespread attention from both the International Chemical Weapon Convention and the Biological and Toxin Weapons Convention.There is an urgent demand for the development of efficient detection and detoxification countermeasures against Abrin to adress its potential threats to human health and public safety.This review,based on clustering analysis of literature and on knowledge of the structures of various subtypes of Abrin,provides an overview of the analysis and detection techniques,the mechanism of toxicity,and detoxification countermeasures against Abrin.It concludes with an examination of the challenges and emerging trends in this field.The main analysis and detection techniques of Abrin include affinity-based analysis,physico-chemical-based analysis,and activity-based detection techniques.The challenges and developments in this field are also outlined.There is a pressing need to establish sensitive,specific,and accurate methods of measurement that are tailored to the structure and activity of Abrin in order to precisely assess and mitigate the toxin threat.Unfortunately,no effective antidotes have been deployed so far,with medical treatments confined to symptomatic care.Research and development of neutralizing antibodies remain stands as the most promising strategy for counteracting Abrin intoxication.

Background: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.