ObjectiveTo analyze the risk factors of dementia among healthy elderly individuals in the middle of their lives. MethodsA total of 175 participants aged 55 to 75 from two communities in Beijing were included from July, 2021 to April, 2023. Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) related risk factors and other demographic data were collected. According to the CAIDE assessment, participants with scores ≥ 9 were as high-risk group, and those with scores < 9 were as low-risk group. They were evaluated with Stroop Color Word Test (SCWT), two elements 1-back task paradigm and the revised Trail Making Test (TMT); measured the grip strength, 30 s forearm flexion tests and five sit-to-stand tests; the average step speed and step length of a 10-meter walk were recorded. ResultsThe average total score of CAIDE was 9.86 in the high-risk group, and was 4.95 in the low-risk group. There was no difference in age between two groups (P = 0.188). There were differences in the proportion of participants of male, less than seven years' education, systolic blood pressure > 140 mmHg, cholesterol > 6.5 mmol/L, body mass index > 30 kg/m², and lack of physical activity between two groups (χ² > 3.116, P < 0.05). The grip strength (t = -4.174), walking speed (t = -2.414), SCWT accuracy (Z = -2.684) were all worse in the high-risk group than in the low-risk group (P < 0.05). Logistic regression analysis showed that walking speed (OR = 25.483), grip strength (OR = 1.133) and SCWT accuracy (OR = 37.430) were independent influencing factors of dementia (P < 0.05). ConclusionWeaker grip strength, slower gait speed and worse inhibitory control might be independent influencing factors of dementia.

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective:To analyze the role of learning engagement and learning burnout in the relationship between supervisors' guidance and the personal ability of postgraduates in the Professional Master's Program in Clinical Medicine.Methods:A total of 4 016 postgraduates in the Professional Master's Program in Clinical Medicine from 61 colleges were surveyed in 2020. Common method bias was assessed using the Harman's single factor test and total score was determined by the entropy weight method. Causality and mediation effect were analyzed by linear regression, and mediation effect was tested by Bootstrapping.Results:The average scores of supervisors' guidance, learning burnout, learning engagement and personal ability were (4.13±0.87), (2.49±1.11), (3.88±0.83), and (3.71±0.78), respectively. Supervisors' guidance significantly and positively impacted learning engagement ( β=0.689, P<0.001) and personal ability ( β=0.504, P<0.001). Learning engagement played a partial mediating role (89.30% of mediation effect) between supervisors' guidance and personal ability. Learning burnout (interaction term β=0.078, P<0.001) positively regulated the relationship between supervisors' guidance and learning engagement. Conclusions:Learning engagement can mediate the effect of supervisors' guidance on the personal ability of postgraduates in the Professional Master's Program in Clinical Medicine, and learning burnout positively regulates the effect of supervisors' guidance on learning engagement. Strengthened supervisors' guidance, increased attention to students' learning burnout, and enhanced learning engagement can further improve the personal abilities of postgraduates in the Professional Master's Program in Clinical Medicine.

Objective:To investigate the "burnout-engagement continuum" status of postgraduate supervisors of the Professional Master's Program in Clinical Medicine and to identify key populations.Methods:From October to November 2023, an anonymous online questionnaire survey was conducted to determine the "burnout-engagement continuum" status of postgraduate supervisors of the Professional Master's Program in Clinical Medicine. The scores of different dimensions of job burnout are expressed as mean±standard deviation, and the distribution of supervisors of different status is presented in frequency and percentage. All data analyses were performed in R 4.3.1. Distribution of the five profiles among supervisors of different status was compared using the chi-square test and compared pairwise using the Bonferroni method.Results:A total of 2 664 valid questionnaires were collected. The scores of emotional exhaustion, cynicism and personal accomplishment were（2.46±0.95),（1.74±0.89), and（4.23±0.90), respectively. The prevalence of job engagement, inefficacy, overexertion, disengagement, and burnout among the supervisors were 42.76%（1 139/2 664), 43.54%（1 160/2 664), 33.03%（880/2 664), 14.71%（392/2 664), and 13.66%（364/2 664), respectively. In terms of demographics, the distribution of the "burnout-engagement continuum" was significantly different by age, sex, marital status, and highest education level（ P<0.05). In terms of work-related characteristics, the distribution of the "burnout-engagement continuum" was significantly different by income, professional title, administrative position, and working hours on weekdays and holidays（ P<0.05). The distribution of engagement, inefficacy, and overexertion was significantly different between the eastern and western regions（ P<0.05). Conclusions:There is a high percentage of individuals with burnout among postgraduate supervisors of the Professional Master's Program in Clinical Medicine, and inefficacy is a common negative state. Supervisors who work in the western regions, are under 45 years of age, are male, are married, have a doctorate degree, hold associate senior professional title, have lower relative income, are not holding administrative duties, and work more than 10 hours on workdays and more than 4 hours on holidays are key populations that require increased attention. The psychological state of supervisors can be improved by providing them with more resources, work benefits, and incentives.

Objective:To investigate the current status of and relationship between practice efficacy, professional identity, and anxiety among public health master's graduates.Methods:From a national survey on the satisfaction with education of fresh medical master's graduates conducted from June to July, 2022, we selected 461 master's graduates of public health with internship experience from 49 institutions. With the use of SPSS 21.0, we compared the scores of practice efficacy, professional identity, and self-rated anxiety by personal characteristics through t-tests and analysis of variance; and explored the mediating role of anxiety in the relationship between practice efficacy and professional identity through stratified regression analysis. Results:The public health master's graduates scored (3.47±1.23) points for anxiety, (3.92±0.88) points for practice efficacy, and (4.33±0.77) points for professional identity. The score of anxiety differed significantly by sex, the degree of being affected by public health emergencies/major outbreaks, and internship initiative (all P<0.05). The score of practice efficacy was significantly different by sex, the type of institution, the degree of being affected by public health emergencies/major outbreaks, and internship initiative (all P<0.05). The score of professional identity differed significantly by sex, the type of institution, major transfer, the degree of being affected by public health emergencies/major outbreaks, internship initiative, and internship duration (all P<0.05). Professional identity was positively correlated with practice efficacy ( r=0.652, P<0.01) and negatively correlated with anxiety ( r=-0.213, P<0.05). The stratified regression results showed that practice efficacy positively influenced professional identity ( β=0.782, P<0.001), and anxiety partially mediated the relationship between the two ( β=-0.104, P<0.05). Conclusions:Anxiety plays a mediating role in the relationship between practice efficacy and professional identity, suggesting that reducing anxiety can help enhance practice efficacy to promote the professional identity of public health master's graduates.

Objective:To investigate the enrollment scale and distribution of Master's Degree in Pediatrics programs in China, and to provide a reference for promoting pediatric education and disciplinary development.Methods:Data on colleges and universities authorized to award Master's Degree in Pediatrics in 2023 were collected, sorted, and analyzed for the number, structure, distribution, and enrollment scale and direction of these institutions using descriptive statistics.Results:Among the 117 clinical medicine academic master's degree programs in China, 72 enroll pediatric academic master's degree candidates, with an enrollment of 260 students. Among the 120 master's degree programs in clinical medicine, 104 enroll professional master's degree candidates, enrolling 1 195 students. Enrollment is mainly concentrated in East China, "non-double first-class" colleges and universities, medical colleges and universities with subject level B, and enrollment is carried out in the direction of secondary disciplines.Conclusions:The number of colleges and universities authorized to award Master's Degree in Pediatrics was small, and the distribution of these colleges and universities was unbalanced. The enrollment scale was small and the orientation of Professional Master's Degree was not reasonable. Some colleges and universities were authorized to award Master's Degree in Pediatrics, but did not enroll any students. It is suggested to increase the number of colleges and universities authorized to award Master's Degree in Pediatrics and strengthen the staffing of pediatric departments. The aim is to expand the enrollment scale of candidates for Master's Degree in Pediatrics, improving the differential training of candidates for Academic Master's Degree and Professional Master's Degree, and attach importance to the construction of pediatrics.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

ObjectiveTo visually analyze the research hotspots and future development trends in the field of rehabilitation of chronic respiratory diseases domestic and overseas in the last decade. MethodsLiteratures about rehabilitation of chronic respiratory disease from 2011 to 2021 were retrieved. The Physiotherapy Evidence Database (PEDro) was used to access the quality of the literatures, and CiteSpace 5.8.R3 was used to analyze the number of publications and keywords. ResultsA total of 2 477 English articles and 3 308 Chinese articles were included. The overall volume of literature published in the field of rehabilitation of chronic respiratory diseases domestic and overseas showed a fluctuating increase. A total of 63 English articles met the requirement of medium-high quality with a score of four to nine on the PEDro scale, and the overall average score was 5.44. A total of 78 domestic articles scored five to eight, and the overall average score was 5.21. Domestic research in this field mainly focused on the pulmonary rehabilitation methods for patients with chronic obstructive pulmonary disease (COPD) and their effects on patients' quality of life and lung function, the process of development of heart-related diseases complicated by COPD, and the effects of nursing interventions, community rehabilitation and health education for chronic respiratory diseases, and exploration of precise pulmonary rehabilitation assessment, etc. In contrast, foreign countries mainly studied the physical activity and exercise capacity of patients with chronic respiratory diseases, emphasizing the self-management of patients, and focused on the cross-sectional research of other diseases such as combined aortic stenosis, and made "physical activity" and "exercise" as the frontier of research. ConclusionOverseas pulmonary rehabilitation programmes involve a wide range of chronic respiratory diseases, requiring multidisciplinary teamwork, strengthening patient self-management at home and focusing on changes in physical activity, motor function and quality of life after exercise, while the focus is on pulmonary rehabilitation in hospitalized COPD patients, also including the role of traditional Chinese exercise in China.

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals ; Berberine/therapeutic use* ; Fatty Liver ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Necrosis