Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells， and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma， amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention， showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy， its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice， in order to provide new ideas for immunotherapy for liver cancer.

Objective: To analyze the trends in disease burden of tuberculosis among children under 5 years of age in China from 1990 to 2021, so as to provide insights for future tuberculosis control measures among children in China. Methods: Based on the Global Burden of Disease (GBD) 2021 datasets, the incidence, prevalence, mortality and disability adjusted life year(DALY) of tuberculosis of children under 5 years of age in China and globally were collected from 1990 to 2021. The incidence, prevalence, mortality and DALY rate of tuberculosis were compared by genders and types. In addition,the annual percent change(APC) and the average annual percent change(AAPC) of children s tuberculosis burden in China and globally from 1990 to 2021 were calculated by using the Joinpoint regression model, and the changing trends were analyzed. Results: The numbers of incident, prevalent and dead tuberculosis cases were 9 700, 8 477 800 and 200 among children under 5 years of age in China in 2021, and the DALY due to tuberculosis were 27 100 person years. There were significant reductions in incidence, prevalence, mortality and DALY rate of tuberculosis among children under 5 years of age in China ( AAPC =-5.45%, -1.14%, -12.37%, -11.34 %) and globally( AAPC =-2.38%, -1.41%, -4.66%, -4.56%), and the reductions in the incidence, mortality and DALY rate were more significant in China than globally ( P <0.05).In 1992 and later, the numbers of incident, prevalent and dead tuberculosis cases and the DALY of tuberculosis were higher among male than among female. In addition, the disease burden of drug susceptible tuberculosis appeared a tendency of downward in China from 1990 to 2021, while the incidence and prevalence of extensively drug resistant tuberculosis rose since 2015. Conclusions The disease burden of tuberculosis remarkably reduced among children under 5 years of age in China from 1990 to 2021. However, the burden of disease due to multidrug resistant tuberculosis appeared an upward trend recently. Increased attention is required to be paid to the prevention and control of tuberculosis among children and improved diagnosis and treatment of drug resistant tuberculosis are recommended.

Objective To investigate the effect of high definition transcranial direct current stimulation(HD-tDCS)at different stim-ulation timings(online and offline)on finger motor skill learning in healthy adults. Methods From March to November,2022,31 right-handed male participants were recruited from Shenyang Sport Uni-versity and randomly assigned to three groups,who received online,offline or sham HD-tDCS respectively dur-ing the three-day sequential visual isometric pinch task learning process.The daily motor skill learning gains,to-tal motor skill learning gains and speed-accuracy function(SAF)were observed. Results The daily motor skill learning gains increased in all the groups,and it was the best in the online group(F=24.692,P<0.001);the learning gains were better in the online group than in the offline group(t=4.732,P<0.001)and the sham group(t=3.839,P=0.004)on the third day.The total motor skill learning gains were ranked as the online group=the offline group>the sham group.SAF data indicated that the online group outper-formed both the offline and sham groups. Conclusion HD-tDCS can promote the finger motor skill learning in healthy adults,and online HD-tDCS is more effec-tive.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To analyze the clinical application of different diagnostic methods for heart failure with preserved ejection fraction (HFpEF) in maintenance hemodialysis (MHD) patients.Methods:It was a single-center retrospective cohort study. Uremia patients who underwent hemodialysis at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2020 to June 2021 were enrolled. The demographic characteristics, laboratory indicators, and echocardiography parameters were collected. The 2016 European Society of Cardiology (ESC) criteria, H 2FPEF score [composite score based on weighted scores of heavy (H), hypertensive (H), atrial fibrillation (F), pulmonary hypertension (P), elder (E), and filling pressure (F)], and Heart Failure Association (HFA) -PEFF score [including pre-test assessment (P), echocardiography and natriuretic peptide score (E), functional testing (F) and final aetiology (F)] were used to diagnose HFpEF, respectively, and the difference of three diagnostic methods was compared. The association between HFpEF diagnosed by the three methods and poor outcomes (all-cause death, cardiovascular death) was analyzed. Results:A total of 160 MHD patients were included, whose age was (58.5±13.4) years, median dialysis age was 5.0 (2.3, 9.6) years, median H 2FPEF score was 2 (1, 3), median HFA-PEFF score was 4 (3, 5), and 92 (57.5%) were males. Of these patients, 118 patients (73.8%) met the 2016 ESC criteria for diagnosis of HFpEF, 4 (2.5%) met H 2FPEF score for diagnosis of HFpEF, and 56 (35.0%) met HFA-PEFF score for diagnosis of HFpEF. The consistency of three methods in diagnosing HFpEF was poor with κ values of 0.018 between ESC criteria and H 2FPEF score, 0.322 between ESC criteria and HFA-PEFF score, and 0.056 between H 2FPEF score and HFA-PEFF score. After a median follow-up of 2.6 years, 20 (12.5%) of the 160 MHD patients died. The Kaplan-Meier survival analysis showed a significant difference in mortality between patients diagnosed with HFpEF and those without using the H 2FPEF score (Log-rank test, χ2=6.95, P=0.008). After adjusting for demographic and clinical parameters, multivariate Cox regression analysis showed that HFpEF diagnosed by HFA-PEFF score was associated with all-cause mortality ( HR=2.73, 95% CI 1.07-6.98, P=0.036) and cardiovascular mortality ( HR=4.77, 95% CI 1.31-17.30, P=0.018). Conclusions:The 2016 ESC criteria, H 2FPEF score, and HFA-PEFF score have high heterogeneity and poor consistency in diagnosing HFpEF in MHD patients. Among the three diagnostic methods, only the diagnosis based on HFA-PEFF score is associated with the prognosis of MHD patients. The HFA-PEFF score can be used to assess the risk of HFpEF in MHD patients, and more clinical studies are needed to further verify it in the future.

Objective:This study aimed to assess the awareness of trainees in physician standardized training towards the consequences of scientific misconduct and identify the main influencing factors, additionally, to provide targeted suggestions.Methods:A questionnaire survey was conducted among 6 200 trainees from 17 National standardized training bases for residencies in Guangxi. The cognitive status of the consequences of scientific misconduct were analyzed and factors affecting trainees' cognition were examined in terms of grade, education level, research experience, publication experience, research integrity training experience, and research integrity knowledge level.Results:The findings indicated that the awareness of trainees towards the consequences of scientific misconduct requires improvement. Notably, trainees from the 2020 and 2021 grade cohorts, with a master′s degree or above, having led research projects, having participated in research integrity training, and with a high level of research integrity knowledge scored higher on the cognitive assessment of the impact of research misconduct.Conclusions:Training bases should prioritize the education of research integrity among trainees, enhance their identification with scientific research integrity, raise their awareness of the seriousness of the consequences of scientific misconduct, and uphold the belief of adhering to the bottom line of academic ethics.

Objective:To analyze the correlation between cuproptosis genes and immune infiltration during the occurrence and development of multiple sclerosis(MS),and to predict the traditional Chinese medicine,to provide theoretical basis for the mecha-nism study of cuproptosis in MS immune infiltration and Chinese medicine to intervene in immune regulation.Methods:The gout chip of MS was downloaded from the GEO database and standardized;based on the processed data,immune cells and functions were ex-tracted and quantified,and the correlation and differences of immune cells and functions were analyzed;at the same time,cuproptosis genes related to MS were screened out,a risk model was constructed,and enrichment analysis was carried out;the prediction of cu-proptosis genes and immune-related biological processes were carried out.Results:① Among immune cells,T follicular helper cell and B cell showed the strongest positive correlation;among the immune functions,parainflammation and typeⅠIFN reponse showed the strongest positive correlation;②B cell,T helper cell and human leukocyte antigen were lowly expressed in MS patients,while major histocompatibility complex class Ⅰ,parainflammation and typeⅠIFN response were significantly expressed;③ The cupropto-sis genes associated with MS were SLC31A1,PDHA1,NLRP3,MTF1,GLS and DBT,of which DBT was the most likely risk factor for MS;④The occurrence and development of MS involves biological processes such as IL-4 production,T-helper cell differentiation,and acute inflammatory response,which were related to pathways such as arginine biosynthesis,citrate cycle,and propanoate metabo-lism;⑤Banxia,Danshen,Jianghuang and other traditional Chinese medicines may be used as potential molecular drug sources.Con-clusion:The expression of cuproptosis gene is closely related to MS-related immune cells and functions,which can provide support for the basic research of MS.