Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.

Objective To explore the potential categories and influencing factors of dietary behavioral adherence trajectories in young and middle-aged patients with type 2 diabetes mellitus.Methods A convenience sampling method was used to investigate 277 young and middle-aged patients with type 2 diabetes mellitus admitted to the Department of Endocrinology of a tertiary A hospital in Huai'an City,China,from September 2022 to March 2023.The baseline data were collected using a general information questionnaire,the Dietary Behavioral Compliance Scale for Patients with Type 2 Diabetes Mellitus,the Diabetes Self-Efficacy Scale,the Diabetes Knowledge Text,the Health Beliefs Questionnaire,and the Family APGAR Index Questionnaire.The baseline information was collected on the patients'behavioral adherence trajectories a day prior to hospital discharge(T0),a week post-discharge(T1),a month post-discharge(T2),and 3 months post-discharge(T3)to assess the level of patients'dietary behavioral adherence,using latent variable growth mixed models to identify trajectory categories,and univariate and multivariate logistic regression to analyze the influences on dietary adherence trajectories.Results A total of 3 trajectories of dietary behavior adherence in young and middle-aged patients with type 2 diabetes mellitus were identified,namely,low adherence-fluctuating group(49.8%),high adherence-slowly regressing group(31.4%),and medium adherence-continuously rising group(18.8%),and the results showed that age,literacy level,self-efficacy,health beliefs,and family caring were the factors influencing potential categories of dietary behavioral adherence for young and middle-aged patients with type 2 diabetes mellitus.Conclusion There is heterogeneity in the adherence trajectories of young and middle-aged patients with type 2 diabetes mellitus,and healthcare professionals can develop targeted interventions according to the influencing factors of the trajectory categories in order to improve their adherence.

Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective Based on the bio-psycho-social model of functioning and health of International Classification of Function-ing,Disability and Health(ICF)framework,this paper systematically analyzes rehabilitation-related policy docu-ments of the World Health Organization(WHO)to explore the theoretical and policy principles,service systems,priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment. Methods Under literature research and policy analysis methods,this paper systematically reviewed the functioning and health framework of ICF,relevant WHO policy reports and American Speech and Hearing Association technical documents,analyzed the current status and needs of rehabilitation services in China,and proposed a theoretical framework,priority areas,and main policy and technical measures for constructing an ICF-based speech and lan-guage rehabilitation service system for children with hearing impairment. Results There were eight major principles for the development of speech and language rehabilitation for children with hearing impairment:child-centered and respect for individual differences,life-cycle support and promoting con-tinuous development,evidence-based practice,multidisciplinary collaboration,building family participation sup-port networks,promoting integrated education and social participation,focusing on cultural sensitivity,and tech-nology-empowered rehabilitation innovation.Five service systems were elaborated,including comprehensive ear-ly screening,diagnosis,and intervention system;family and social support system;multidisciplinary team servic-es system;comprehensive,multi-level speech and language rehabilitation service system;and digitally empow-ered services to build new rehabilitation service models.The priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment were also dis-cussed. Conclusion Based on the bio-psycho-social model of functioning and health of ICF,comprehensive,personalized,con-tinuous,high-quality and universally accessible speech and language rehabilitation services can be developed by implementing measures,such as strengthening policy support,improving service systems,cultivating multidisci-plinary professionals,promoting digital empowerment technologies and enhancing support system,to promote the overall development,social participation and quality of life for children with hearing impairment.

Background::Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients.Methods::The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.Results::A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram.Conclusions::We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

Objective:To investigate the current status of the teaching methods used in the integrated basic and clinical courses and the approaches for improving such teaching methods, and to improve the teaching quality of the integrated basic and clinical courses for "4+4" Medical Doctor Program in Peking Union Medical College.Methods:Students in the Class 2020 of "4+4" Medical Doctor Program who completed the integrated courses from September 2020 to August 2021 were enrolled as subjects. Questionnaire surveys and interviews were performed for the subjects in terms of class hours, integration effect, and self-learning methods. R4.0.0 software was used to perform a statistical analysis of data.Results:The mean weekly class hours of existing modules were (27.59±2.61) hours per week, which was higher than the expectation of students. There was a negative linear correlation between weekly class hours and mean satisfaction score of each module ( r=-0.71, P=0.022). The integration of basic and clinical medical courses had a mean satisfaction score of 2.652. The median preview time for case-based learning/problem-based learning was 30 minutes. Conclusions:In the reform of the integration of basic and clinical medical courses, it is crucial to select and apply proper teaching methods. In order to further improve teaching effect, it is advised to reduce the class hours of theoretical lectures and carefully design and prepare learning materials, and the teaching contents should be organized according to the internal logic of knowledge and the association between clinical knowledge and the knowledge learned during the stage of basic medicine.

Objective To explore the effect of multiparameter electroencephalogram(EEG)-guided anesthesia management on EEG burst suppression(BS)and postoperative delirium(POD)in elderly patients undergoing lower abdominal laparoscopic surgery.Methods A total of 100 elderly patients,48 males and 52 females,aged 65-85 years,BMI 18.5-28.0 kg/m2,and ASA physical status Ⅱ or Ⅲ,were enrolled for lower abdominal surgery under general anesthesia.Patients were randomly divided into two groups:multiparameter group and single parameter group,50 patients in each group.In multiparameter group,multiparameter EEG monitoring with patient statu index(PSI),spectral edge frequency(SEF),burst suppression ratio(BSR)and density spectral array(DSA)were used to guide the depth management of anesthesia.In single parameter group,single parameter PSI was used to guide the depth management of anesthesia.The total area under the hypotensive threshold of MAP(AUTMAP)was calculated,and the amount of anesthetic used during the operation and the use of vasoactive drugs,duration of anesthesia,extu-bation time,duration of PACU stay,and postoperative hospitalisation days were recorded.HR,MAP,PSI,and SEF were recorded before the induction of anesthesia,5 minutes after induction of anesthesia,5,30,and 60 minutes after incision,and at the end of surgery.The incidence,duration,and maximum BSR of in-traoperative BS,as well as the incidence of POD 1,2,and 3 days after surgery were recorded.Results There was no significant difference in AUTMAP values between the two groups.Compared with single parame-ter group,intraoperative propofol and remifentanil dosage were significantly decreased(P＜0.05),awak-ening time,PACU stay,and postoperative hospitalization time were significantly shorter in multiparameter group(P＜0.05),the PSI was significantly increased 5,30,and 60 minutes after incision and at the end of surgery,and the SEF was significantly increased 5 minutes after induction of anesthesia,5,30,and 60 minutes after induction and the end of surgery(P＜0.05).Compared with single parameter group,inci-dence of intraoperative BS was significantly decreased,duration of BS was significantly shorter,smaller maximum BSR was significantly decreased,and incidence of POD on 1 day after surgery in multiparameter group(P＜0.05).Conclusion Anesthesia management guided by multiparameter EEG can inhibit the oc-currence of BS,mitigate the degree of BS,and reduce the incidence of POD in elderly patients undergoing abdominal surgery.

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.