Objective: To analyze the association between drinking behaviors and anxiety symptoms, with the mediating role of insomnia symptoms among college freshmen, so as to provide a reference basis for reducing the occurrence of anxiety symptoms in college freshmen. Methods: From October to December 2021, 31 856 freshmen were selected by the purposive sampling method in 22 colleges across 11 provinces (Fujian, Jiangsu, Guangdong, Henan, Anhui, Hubei, Shanxi, Jiangxi, Shaanxi, Yunnan, Chongqing) in China. The Semi quantitative Food Frequency Questionnaire was used to investigate college freshmen drinking behaviors. The Depression Anxiety Stress Scale 21 and the Insomnia Severity Index were used to assess anxiety symptoms and insomnia symptoms in college freshmen. The generalized linear model was employed to analyze the association between drinking behaviors and anxiety symptoms in college freshmen, and the structural equation modeling was used to assess the mediating effect of insomnia symptoms on the association. Results: The detection rate of anxiety symptoms among college freshmen was 28.2%, the detection rates of the mild, moderate, severe and extremely severe were 6.6%, 15.9%, 3.2% and 2.6%, respectively. While 23.6% of college freshmen reported drinking in the past month, the rates were 39.8% among boys and 15.9% among girls. After adjusting for demographic variables (ethnicity, education, major, etc.) and confounding variables (self evaluation of learning burden, number of close friends, screen time, etc.), the results of generalized linear model analysis showed that beer consumption was associated with anxiety symptoms in college freshmen( β =0.09, 95% CI =0.04-0.14), girls( β =0.14, 95% CI =0.07-0.21) and those aged 19-20 years ( β =0.12, 95% CI =0.05-0.19)(all P <0.05). Red wine consumption was associated with anxiety symptoms in male students ( β =0.13, 95% CI =0.02-0.24, P <0.05). Alcohol and beer consumption were associated with insomnia in college freshmen[ β (95% CI ) =0.22(0.08-0.36),0.31(0.23-0.39),both P <0.01]. Insomnia symptoms partially mediated the association between drinking behaviors and anxiety symptoms among college freshmen with a mediating effect value of 0.05, accounting for 50.49% of the total effect. Conclusions Insomnia symptoms partially mediates the association between drinking behaviors and anxiety symptoms in college freshmen. Measures should be taken to simultaneously intervene in the drinking behaviors and insomnia symptoms of college freshmen to prevent the occurrence of their anxiety symptoms.

The active components in traditional Chinese medicine （TCM） generally have problems such as poor solubility and low bioavailability， which seriously restrict their clinical efficacy. In recent years， TCM nano-self-assembly based on the non-covalent interactions between molecules has become the research frontier in this field because it can spontaneously form an orderly structure and improve the insoluble components in the body. Moreover， TCM nano-self-assembly has shown unique advantages in the treatment of fibrosis， inflammatory and immune diseases， infectious diseases， and cancer. This article summarizes the research context， structural system， and potential as a pharmacological substance basis of TCM nano-self-assembly by reviewing recent published studies， with focuses on the application of TCM nano-self-assembly in the treatment of diseases from single components to complex systems. In addition， this article summarizes its advantages， mechanism characteristics， and main challenges faced. At present， this field still faces issues such as insufficient mechanism research， a lack of in-depth understanding of the competitive assembly rules of multiple components， difficulty in quality control， unclear in vivo processes and safety， and obstacles to clinical translation. To address these issues， this article proposes a series of solutions， including introducing molecular dynamics simulation and artificial intelligence to predict assembly behavior， using experimental techniques to analyze non-covalent interactions， establishing a comprehensive evaluation system with multiple indicators， using isotope labeling and in vivo imaging techniques to dynamically track in vivo processes， conducting standardized safety evaluation， promoting the filing of hospital preparations and new drug applications， and strengthening early communication between research and regulation. Finally， this article points out the future development directions， aiming to provide reference for subsequent research and clinical translation.

The active components in traditional Chinese medicine （TCM） generally have problems such as poor solubility and low bioavailability， which seriously restrict their clinical efficacy. In recent years， TCM nano-self-assembly based on the non-covalent interactions between molecules has become the research frontier in this field because it can spontaneously form an orderly structure and improve the insoluble components in the body. Moreover， TCM nano-self-assembly has shown unique advantages in the treatment of fibrosis， inflammatory and immune diseases， infectious diseases， and cancer. This article summarizes the research context， structural system， and potential as a pharmacological substance basis of TCM nano-self-assembly by reviewing recent published studies， with focuses on the application of TCM nano-self-assembly in the treatment of diseases from single components to complex systems. In addition， this article summarizes its advantages， mechanism characteristics， and main challenges faced. At present， this field still faces issues such as insufficient mechanism research， a lack of in-depth understanding of the competitive assembly rules of multiple components， difficulty in quality control， unclear in vivo processes and safety， and obstacles to clinical translation. To address these issues， this article proposes a series of solutions， including introducing molecular dynamics simulation and artificial intelligence to predict assembly behavior， using experimental techniques to analyze non-covalent interactions， establishing a comprehensive evaluation system with multiple indicators， using isotope labeling and in vivo imaging techniques to dynamically track in vivo processes， conducting standardized safety evaluation， promoting the filing of hospital preparations and new drug applications， and strengthening early communication between research and regulation. Finally， this article points out the future development directions， aiming to provide reference for subsequent research and clinical translation.

OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae （CRKP） infection， develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae （CSKP） during the same period as the modeling group. Using the same criteria， data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis， LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling， and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic （ROC） curves and calibration plots. RESULTS A total of 530 patients were enrolled， with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection （P＜0.05）. The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations， respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Alzheimer's disease(AD)is an age-related neurodegenerative disease that mainly manifests clinically as progressive functional impairments in cognition,memory,and language.With the accelerated transition toward an older population in China,the number of people suffering from AD in China is increasing.The exact pathogenesis of AD remains unclear,with current therapeutic strategies mainly limited to symptomatic treatments.Animal models are important tools for preclinical research,enabling explorations of molecular mechanisms,behavioral functions,and treatment strategies of diseases.Future mechanistic research and drug development of AD should involve the establishment of animal models that are consistent with clinical pathological characteristics.This review summarizes the AD animal models commonly used in research,providing details on the strains,age,modeling method and doses.It also discusses research on traditional Chinese medicine(TCM)components and their pharmacodynamic mechanisms in related AD animal models,aiming to provide references for the development of new animal models and in-depth exploration of the specific pharmacological activities,targets,metabolic pathways,and clinical applications of each TCM component.

Objective:To investigate the characteristics of clinical manifestations and parameters of 24 hour multichannel intraluminal impedance and pH monitoring (24 h MII-pH) in patients with low mean nocturnal baseline impedance (MNBI) of proximal esophagus.Methods:From November 4, 2014 to February 18, 2024, 308 patients who underwent 24 h MII-pH at Peking University First Hospital due to typical gastroesophageal reflux disease symptoms and(or) extra-esophageal symptoms were retrospectively enrolled. MNBI at 17 or 15 cm above the lower esophageal sphincter (LES) < 2 292 Ω was defined as low proximal esophageal impedance (LPEI), both MNBI at 17 and 15 cm above the LES ≥ 2 292 Ω was defined as normal proximal esophageal impedance (NPEI). The 24 h MII-pH parameters were compared between patients with LPEI and patients with NPEI, as well as the incidence of extra-esophageal symptoms. And the 24 h MII-pH parameters were compared between patients with and without extra-esophageal symptoms. Independent sample t-test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among the 308 patients, 71 patients with LPEI, 236 patients with NPEI, and 1 patient was excluded due to missing the 24 h MII-pH data; and there were 215 patients with extra-esophageal symptoms and 93 without extra-esophageal symptoms. The proportion of extra-esophageal symptoms in the LPEI patients was higher than that in the NPEI patients(81.7% (58/71) vs. 66.1% (156/236)), the times of postprandial total reflux, postprandial acid reflux detected by impedance, proximal total reflux, and proximal acid reflux in the LPEI patients were more than those in the NPEI patients (22.5 (22.8) vs. 17.0 (19.0), 10.5 (13.3) vs. 7.0 (13.0), 9.0 (12.0) vs. 5.0 (11.0), 5.0 (10.0) vs. 3.0 (7.0)), and the differences were statistically significant( χ2=6.28, Z=-1.99, -2.06, -2.26 and -2.44; all P<0.05). The times of weak acidic reflux at supine position, proximal total reflux, proximal acid reflux, and proximal non-acid reflux of the patients with extra-esophageal symptoms were more than those in patients without extra-esophageal symptoms (2.0(5.0) vs. 1.0(4.0), 6.0(13.0) vs. 4.0(10.0), 4.0(10.0) vs. 3.0(7.0), 2.0(4.0) vs. 1.0(3.0)), the MNBI at 15 cm above the LES in patients with extra-esophageal symptoms was lower than that in patients without extra-esophageal symptoms ((3 222.4±1 018.7) Ω vs. (3 512.3±1 032.1) Ω), and the differences were statistically significant ( Z=-2.32, -2.25, -2.00 and -2.13, t=-2.28; all P<0.05). Conclusions:LPEI patients have higher proportion of extra-esophageal symptoms, more times of proximal and postprandial acidic reflux. The proximal esophageal impedance and proximal reflux parameters should be emphasized in the diagnosis and treatment of patients with extra-esophageal symptoms.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Objective:To explore the expression of CD14 in peripheral blood monocytes to predict the prognosis of patients with severe COPD complicated with pulmonary infection.Methods:A total of 122 patients with severe COPD and pulmonary infection diagnosed and treated in East Lianyungang Hospital from January 2019 to February 2022 were selected as co-infection group,127 pa-tients with severe COPD were selected as COPD group,and 62 healthy subjects in physical examination during the same period were selected as control group.After 30 days of follow-up,patients in co-infected group were divided into death group(n=16)and survival group(n=106)according to prognosis during hospitalization.Membrane CD14(mCD14)related parameters of control group,COPD group and co-infected group were compared.Dynamic changes of mCD14 related parameters were compared between death group and survival group at day 1,3,5,7 and 14 after diagnosis.Cox proportional hazard regression was used to analyze the independent risk factors of death in patients with severe COPD complicated with pulmonary infection after 30 days.Predictive values of CD14%,CD14MFI and CD14IND on prognostic death were analyzed by ROC curve,and the area under the curve(AUC)was compared.Ka-plan-Meier method was used to draw survival curve to compare the survival of patients with different CD14IND levels.Results:Com-pared with control group,CD14%,CD14MFI and CD14IND in COPD group and co-infection group were significantly decreased;com-pared with COPD group,CD14%,CD14MFI and CD14IND in co-infection group were significantly decreased,the differences were statistically significant(P<0.05).Expression of mCD14 in survival group increased steadily during the whole monitoring process,while expression in death group fluctuated at a low level.COPD grade,forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC),forced expiratory volume in 1 second as a percentage of predicted value(FEV1%pred),CD14%,CD14MFI,CD14IND were all risk factors for death in patients with severe COPD complicated with pulmonary infection(P<0.05).CD14%,CD14MFI and CD14IND were negatively correlated with mortality and COPD grade in patients with severe COPD complicated with pulmonary infec-tion,while were positively correlated with FEV1%pred and FEV1/FVC(P<0.001).With CD14IND≤74.36 as cut-off value,the sensi-tivity and specificity of predicting death reached 91.22%and 95.51%respectively.The 30-day survival rate of high-risk group was 68.42%(26/38),which was significantly lower than 95.24%(80/84)of low-risk group(log-rank χ2=10.067,P=0.002).Conclusion:mCD14-related parameters are expected to be the prognostic markers of death in patients with severe COPD complicated with pulmo-nary infection,and the sensitivity and specificity of CD14IND are better than those of CD14%and CD14MFI.