Objective: To analyze the epidemiological characteristics and changing trends of non suicidal self injury (NSSI) behaviors among middle school students in Jiading District of Shanghai, from 2015 to 2023, so as to provide a basis for the development of NSSI prevention and control measures among students. Methods: Using a stratified cluster random sampling method, a total of five times for Shanghai Adolescent Health Risk Behavior Surveys were conducted for every two years in Jiading District of Shanghai from 2015 to 2023. A total of 5 231 middle school students from junior high schools and senior high schools were selected for questionnaire surveys. Intergroup comparisons were performed using the x 2 test or the χ 2 trend test, and the JointPoint 5.0 software was used to analyze the changing trends, with the annual percent change (APC) used for evaluation. A binary Logistic regression model was employed to analyze the related factors of NSSI behavior among middle school students. Results: In 2023, the reported NSSI rate among middle school students in Jiading District was 14.2%. The rate was significantly higher among junior high school students (17.1%) than that among senior high school students (11.1%), and higher among females (19.2%) than that among males (10.0%) ( χ 2=10.04, 23.21, both P <0.01). From 2015 to 2023, the overall reported NSSI rate showed an increasing trend, rising from 8.6% in 2015 to 14.2% in 2023 ( χ 2 trend =22.25), with an APC of 6.64% ( t =3.49), and the APC for girls was 9.79 % ( t =3.20) (all P <0.05). Among students reporting NSSI, the proportion experiencing ≥6 episodes increased from 10.8% in 2015 to 19.2% in 2023 ( χ 2 trend =6.57, P <0.05). Multivariate Logistic regression analysis indicated that girls, junior high school students, those with insomnia, depressive emotion and drinkers had higher risks of NSSI, compared to boys, senior high school students, those without insomnia, non depressive emotion students and non drinkers ( OR =1.71, 1.96, 3.44, 4.76, 1.77, all P < 0.05 ). Conclusions The reported rate of NSSI among middle school students in Jiading District of Shanghai, increased annually from 2015 to 2023, and the proportion of repeated NSSI also showed an upward trend. Early intervention measures targeting middle school students, especially junior high school students and females, should be implemented to prevent and control its occurrence and development.

Objective: To investigate the association between occupational stress and health-related quality of life (HRQoL) among grassroots medical personnels, so as to provide the reference for improving their physical and mental well-being. Methods: From March to May 2024, medical staff from nine street community health service centers in Liangxi District, Wuxi City, Jiangsu Province were selected by a convenient sampling method. Basic information was collected through questionnaire surveys. Occupational stress was assessed using the Core Occupational Stress Measurement Scale. Health utility value and the Visual Analog Scale (EQ-VAS) score were investigated using the European Quality of Life Five-Dimension Five-Level (EQ-5D-5L) questionnaire. The association between occupational stress and HRQoL was analyzed using multiple linear regression model. Results: A total of 909 individuals were surveyed, including 141 males (15.51%) and 768 females (84.49%). The average occupational stress score was (24.41±9.45) points. The average health utility value was (0.96±0.07), with 372 individuals (40.92%) experiencing health problems in at least one dimension. The primarily problems were pain/discomfort and anxiety/depression, with 249 (27.39%) and 265 (29.15%) individuals, respectively. The average EQ-VAS score was (86.62±13.84) points. Multiple linear regression analysis revealed that occupation (nurses, β'=0.101; pharmacists, β'=0.101; medical technicians, β'=0.090), professional title (intermediate, β'=-0.079; associate senior, β'=-0.081; senior, β'=-0.101), and occupational stress (β'=-0.288) were influencing factors for health utility value. Occupation (nurses, β'=0.087; pharmacists, β'=0.146; medical technicians, β'=0.073) and occupational stress (β'=-0.226) were influencing factors for EQ-VAS score. After adjusting for variables such as gender, age, educational level, occupation, professional title, work experience, and monthly income, grassroots medical personnels with higher occupational stress score had lower health utility values (β'=-0.296) and EQ-VAS score (β'=-0.237). Conclusions Occupational stress can reduce the HRQoL among grassroots medical personnels. It is recommended to regularly assess occupational stress levels and intervene early to address their psychological and physical health issues.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

Trastuzumab has improved survival rates in human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC),but drug resistance leads to treatment failure.Natural killer(NK)cell-mediated antibody-dependent cell cytotoxicity(ADCC)represents an essential antitumor immune mechanism of trastuzumab.Traditional Chinese medicine(TCM)has been used for centuries to treat diseases because of its capacity to improve immune responses.Xianling Lianxia formula(XLLXF),based on the principle of"strengthening body and eliminating toxin",exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC.Notably,this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC,as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo inter-vention experiments.Mechanistically,the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible Src homology 2(SH2)containing protein(CISH)expression,which in turn activates the Janus kinase 1(JAK1)/signal transducer and activator of transcription 5(STAT5)pathway.Collectively,these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing pa-tients with HER2-positive BC to trastuzumab.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.

Objective To investigate the progress of two-dimensional echocardiographic parameters in patients with different severity of aortic stenosis.Methods A retrospective analysis was per-formed on 96 patients diagnosed with aortic stenosis with at least 2 times of transthoracic echo-cardiography(interval ≥1 year)in Department of Cardiology,Fourth Medical Center of Chinese PLA General Hospital from March 2017 to December 2023.According to aortic stenosis severity,they were divided into a mild group(72 cases),a moderate group(14 cases)and a severe group(10 cases).Peak pressure gradient(PPG)across aortic valve,Vmax,mean aortic valve pressure gradient(ΔPm),pulmonary artery systolic pressure(PASP)were collected,and the changes and annual progress of these echocardiographic parameters at baseline and before and after follow-up were analyzed.Results The values of IVST,LVPWT,Vmax,aortic valve PPG and ΔPm were sig-nificantly increased in the mild,moderate and severe stenosis groups in turn(P＜0.05,P＜0.01).The values of Vmax,PPG and ΔPm were significantly lower in the mild stenosis group than the moderate and severe stenosis groups,and the LVPWT value was obviously lower in the mild ste-nosis group than the severe stenosis group(P＜0.05).The aortic valve PPG and ΔPm values at follow-up were significantly higher than those before the follow-up in the three stenosis groups(P＜0.05,P＜0.01).After follow-up,the Vmax values in mild and moderate stenosis groups were notably higher than before(P＜0.01).The PASP value at follow-up was significantly higher than before in the severe stenosis group(P＜0.05).The annual progression rate of Vmax,PASP,LVEF were gradually increased in the mild,moderate,and severe stenosis groups(P＞0.05).The annual progression rate of ΔPm was gradually increased in the three groups in turn(2.30±1.77 mm Hg/year vs 2.40±1.18 mm Hg/year vs 6.08±1.70 mm Hg/year,P＜0.05).Conclusion As the severity of baseline aortic stenosis increases,obvious changes are observed in cardiac structure and function.Before and after follow-up,the serious the aortic stenosis severity is,the faster the annual progression rates of Vmax,PPG,LVEF and PASP are.

Objective:To investigate the co-infection and phylogenetic analysis of human rhinovirus (HRV) in 2019 novel coronavirus (2019-nCoV) positive samples.Methods:Ten common respiratory viruses, including HRV were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR) in 7 213 samples of 2019-nCoV positive cases and the co-infection characteristics were analyzed. The VP4/VP2 gene fragment of HRV was amplified and sequenced.Phylogenetic trees were constructed.Results:HRV accounted for 1.34% of the 2019-nCoV positive samples (97/7 213), followed by common coronavirus (0.50%, 36/7 213). The co-infection rate of HRV in 2019-nCoV positive samples was significantly different from that of other viruses ( χ2=318.09, P<0.001). There was significant difference in HRV co-infection rate among different age groups ( χ2=36.77, P<0.001), the peak was in<18 years age group. The co-infection rate of HRV had no significant difference in different seasons. The VP4/VP2 gene fragments of 39 HRV strains (40.21%, 39/97) were successfully sequenced and made phylogenetic analysis. There were 10 strains of HRV-A, 9 strains of HRV-B and 20 strains of HRV-C. Seventeen subtypes were identified, of which B6 (66.67%, 6/9) and C15 (70%, 14/20) were the most prevalent and other subtypes were scattered. Conclusions:The co-infection rate of HRV in patients with 2019-nCoV infection was the highest. The highest co-infection rate was in<18 years age group. Group A, B, and C of HRV were found in 2019-nCoV positive samples, and serotypes present diversity.

Objective:To investigate the relationship between heart rate variability(HRV), deceleration capacity(DC) and cardiovascular metabolic disease(CMD) in children and adolescents with normal weight obesity(NWO).Methods:A total of 200 children and adolescents aged 6-17 who underwent normal physical examination in Chengdu Women′s and Children′s Central Hospital from December 2022 to June 2023 were included in this retrospective case-control study.They were divided into the NWO group, normal weight lean(NWL) group, and overweight-obesity(OW-OB) group according to their body mass index(BMI) and body fat percentage(BF%).Fifty children were enrolled into the NWO group; fifty-one children were enrolled into the NWL group; and 99 children were enrolled into the OW-OB group.All the subjects received 24-hour heart monitoring, and their HRV indexes, such as the standard deviation of N-N interval in normal sinus(SDNN), the standard deviation of the mean value N-N intervals every 5-minute(SDANN), the mean of the standard deviations of all N-N intervals for each 5-minute segment of 24 hours(SDNNindex), the root mean square of successive N-N interval difference(rMSSD), the proportion of N-N 50(the successive N-N interval differences>50 ms) in the total number of N-N intervals(pNN50), and DC were automatically calculated.Blood pressure, fasting blood glucose and blood lipids were measured, and the cardiometabolic risk score(CRS) was obtained through the accumulation of relevant factors.The general data, SDNN, SDANN, SDNNindex, rMSSD, pNN50, DC and CRS of the three groups were compared by variance analysis.Spearman correlation and multivariate Logistic regression were used to analyze the risk factors affecting CRS.Results:There was no significant difference in age, gender and other general information among the three groups(all P>0.05).SDNN in the NWO, NWL, and OW-OB groups were(120.88±16.36) ms, (129.07±16.36) ms, and(109.29±16.38) ms, respectively( F=26.231, P<0.001); SDANN were(64.44±11.61) ms, (66.25±8.34) ms, and(61.70±6.85) ms, respectively( F=5.048, P=0.007); rMSSD were(27.02±3.87) ms, (27.51±5.92) ms, and(25.12±6.78) ms, respectively( F=3.328, P=0.038); pNN50 were(12.62±4.04)%, (13.39±2.26)%, and(11.22±2.93)%, respectively( F=9.099, P<0.001); DC were(4.83±0.20) ms, (4.94±0.33) ms, and(4.63±0.28) ms, respectively( F=23.496, P<0.001)and CRS was 0.94±0.87, 0.69±0.19 and 1.57±1.07, respectively( P<0.01).The differences between the three groups were statistically significant.Spearman correlation analysis showed that BMI( r=0.211, P=0.003) and BF%( r=0.558, P<0.001) were significantly positively correlated with CRS, while SDNN( r=-0.258, P<0.001) and DC( r=-0.499, P<0.001) were significantly negatively correlated with CRS.Multivariate Logistic regression analysis showed that BF%(95% CI: 0.098-0.265, P<0.001) and DC(95% CI: -3.962--1.391, P<0.001) were independent risk factors for predicting CMD. Conclusions:Increased BF% and decreased DC are independent risk factors for CMD.Analysis of body composition and HRV in children and adolescents can help to identify potentially high-risk groups more accurately, intervene early, and reduce the risk of CMD.

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.