Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

OBJECTIVE: To investigate the potential mechanisms of sepsis pathogenesis in intensive care unit (ICU), with a specific focus on the role of skin microbiota, and to evaluate the causal relationships between skin microbiota and ICU sepsis using Mendelian randomization (MR). METHODS: A two-sample MR analysis was performed using skin microbiota genome-wide association study (GWAS) summary data from German population cohorts as exposures, combined with ICU sepsis susceptibility and 28-day mortality GWAS summary data from the IEU OpenGWAS database as outcomes. The primary causal effect estimates were generated using the inverse variance weighted (IVW) method, supplemented by validation through MR-Egger and weighted median approaches. Heterogeneity and pleiotropy tests, along with sensitivity analyses, were conducted to evaluate the robustness of the results. RESULTS: Regarding risk of ICU sepsis, IVW analysis showed that order Pseudomonadales [odds ratio (OR) = 0.93, 95% confidence interval (95%CI) was 0.88-0.98], family Flavobacteriaceae (OR = 0.93, 95%CI was 0.90-0.96), and genus Acinetobacter (OR = 0.96, 95%CI was 0.93-0.99) were significantly negatively correlated with the risk of ICU sepsis (all P < 0.05). There was a significant positive correlation between the risk of ICU sepsis and the presence of β-Proteobacteria (OR = 1.05, 95%CI was 1.00-1.11) and Actinobacteria (OR = 1.05, 95%CI was 1.00-1.11), both P < 0.05. Regarding 28-day mortality of ICU sepsis, IVW analysis showed that phylum Bacteroidetes (OR = 0.92, 95%CI was 0.86-0.99), family Streptococcaceae (OR = 0.92, 95%CI was 0.85-0.98), family Flavobacteriaceae (OR = 0.90, 95%CI was 0.83-0.97), genus Streptococcus (OR = 0.92, 95%CI was 0.86-0.99), ASV016 [Enhydrobacter] (OR = 0.92, 95%CI was 0.87-0.98), and ASV042 [Acinetobacter] (OR = 0.92, 95%CI was 0.88-0.97) were significantly negatively correlated with the 28-day mortality of ICU sepsis (all P < 0.05); family Moraxellaceae (OR = 1.09, 95%CI was 1.00-1.18) and ASV008 [Staphylococcus] (OR = 1.08, 95%CI was 1.03-1.14) was significantly positively correlated with the 28-day mortality of ICU sepsis (both P < 0.05). Sensitivity analysis and MR-PRESSO showed no heterogeneity, pleiotropy, or horizontal pleiotropy between skin microbiota and ICU sepsis risk and 28-day mortality rate. Analysis of confounding factors showed that single nucleotide polymorphisms (SNPs) associated with relevant skin bacteria could independently and causally affect the risk of ICU sepsis or ICU sepsis related mortality rate, independent of other confounding factors. The Steiger test results indicated that the established causal relationship was not due to reverse causality. CONCLUSIONS Skin microbiota composition may influence both sepsis susceptibility and 28-day mortality in ICU settings. Family Flavobacteriaceae demonstrated protective effects against sepsis onset and mortality. These findings provide new perspectives for early detection and management strategies.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Mendelian Randomization Analysis ; Microbiota ; Skin/microbiology* ; Genome-Wide Association Study ; Risk Factors ; Skin Microbiome

Objective:To investigate the correlations between physical, psychological and social frailty in elderly patients with multimorbidity.Methods:This study utilized a mixed method. A questionnaire survey was conducted from February to June 2024, among elderly patients with multimorbidity attending 4 primary health care centers in urban Beijing selected by the convenience sampling method. The FRAIL Frailty Assessment Scale, WHO-5 Index of Well-Being Scale, and HALFT Scale were used to assess the patients′ physical, psychological, and social frailty, respectively. Spearman correlation analysis was used to analyze the correlation between different dimensions of frailty in elderly with multimorbidity. Logistic regression model was used to analyze the factors influencing physical, psychological and social frailty. The elderly with multimorbidity who were assessed to have at least 1 or more types of frailty in the quantitative study were selected for in-depth interviews in the form of online and offline combination. The topics of in-depth interview included the real experience of the different dimensions of frailty, the possible causes and the difficulties caused. The sample size was determined according to the principle of information saturation. Thematic analysis was used to summarize, code and analyze the interview data.Results:A total of 919 participants were included in the quantitative study, with a mean age of (74.09±6.03) years, 329(35.80%) were males and 590(64.20%) were females. The prevalence of physical, psychological, and social frailty was 17.85%(164/919), 21.44%(197/919), 11.21%(103/919), respectively. A total of 21 participants were included in the qualitative study, with a mean age (76.90±5.13)years, 5(23.81%) males and 16(76.19%) females. Spearman correlation analysis showed that physical and psychological frailty were moderately correlated ( r=0.311, P<0.001), psychological and social frailty were weakly correlated ( r=0.218, P<0.001), and physical and social frailty were weakly correlated ( r=0.267, P<0.001). Logistic regression analysis showed that the age, the number of multimorbidities, the psychological frailty and social frailty were the influencing factors for physical frailty (all P<0.05). The gender, number of multimorbidity, type of medication taken, physical frailty and social frailty were influencing factors of psychological frailty (all P<0.05). And age, number of multimorbidities, physical frailty and psychological frailty were influencing factors of social frailty (all P<0.05). A total of 3 themes were extracted through in-depth interviews, namely, "physical and psychological frailty are interrelated""physical and social frailty are interrelated", and "psychological and social frailty are interrelated". Conclusions:The physical, psychological, and social frailty in elderly patients with multimorbidity interacts with each other. Whereas the number of multimorbidities is a common risk factor for all three.

Objective:To analyze the current status, research hotspots, and development trends on the integration of primary care and prevention in China.Methods:This was a bibliometric analysis. Literature related to research on the integration of primary care and prevention in China was retrieved from CNIKI, Wanfang, VIP, Chinese Medical Journal Full Text Database, PubMed, and Web of Science for the period from January 1, 2015, to April 1, 2025. CiteSpace software was used to conduct a visual analysis of publication volume, authors and their collaborations, institutions, and keywords in the included literature.Results:A total of 292 domestic publications on the integration of primary healthcare and public health were analyzed. Research on primary healthcare-public health integration in China exhibited an overall upward trend from 2015 to 2025. Based on publication volume and temporal distribution, domestic research can be categorized into an exploratory phase (2015-2020) and a rapid development phase (2021-2025). The institutions publishing relevant research were predominantly universities and research centers, with a low institutional network density (0.013), indicating relative weak inter-institutional collaboration. The co-occurrence density among authors was 0.013 9. Collaboration predominantly occurred in small clusters, with limited cross-regional cooperation. Keywords that appeared frequently and had an intermediary centrality exceeding 0.1 included chronic diseases (0.40), public health (0.23),health management (0.18), and hypertension (0.17). Keyword clustering analysis showed that the top three categories mainly focused on public health, chronic diseases, and health management. Since 2024, emerging keywords with high burst intensity have included big data, health literacy, primary care hospitals, and infectious diseases.Conclusions:Research on the integration of medical and preventive care at the primary healthcare level in China has entered a stage of rapid development. Current research hotspots focus primarily on chronic disease management, the implementation status and barriers of primary healthcare and prevention integration models. Future research is expected to emphasize the application of intelligent technologies, and the enhancement of public health emergency response capacity.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.

Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P＜0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P＜0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P＜0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P＜0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P＜0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P＜0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P＜0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.

Objective:To investigate the correlations between physical, psychological and social frailty in elderly patients with multimorbidity.Methods:This study utilized a mixed method. A questionnaire survey was conducted from February to June 2024, among elderly patients with multimorbidity attending 4 primary health care centers in urban Beijing selected by the convenience sampling method. The FRAIL Frailty Assessment Scale, WHO-5 Index of Well-Being Scale, and HALFT Scale were used to assess the patients′ physical, psychological, and social frailty, respectively. Spearman correlation analysis was used to analyze the correlation between different dimensions of frailty in elderly with multimorbidity. Logistic regression model was used to analyze the factors influencing physical, psychological and social frailty. The elderly with multimorbidity who were assessed to have at least 1 or more types of frailty in the quantitative study were selected for in-depth interviews in the form of online and offline combination. The topics of in-depth interview included the real experience of the different dimensions of frailty, the possible causes and the difficulties caused. The sample size was determined according to the principle of information saturation. Thematic analysis was used to summarize, code and analyze the interview data.Results:A total of 919 participants were included in the quantitative study, with a mean age of (74.09±6.03) years, 329(35.80%) were males and 590(64.20%) were females. The prevalence of physical, psychological, and social frailty was 17.85%(164/919), 21.44%(197/919), 11.21%(103/919), respectively. A total of 21 participants were included in the qualitative study, with a mean age (76.90±5.13)years, 5(23.81%) males and 16(76.19%) females. Spearman correlation analysis showed that physical and psychological frailty were moderately correlated ( r=0.311, P<0.001), psychological and social frailty were weakly correlated ( r=0.218, P<0.001), and physical and social frailty were weakly correlated ( r=0.267, P<0.001). Logistic regression analysis showed that the age, the number of multimorbidities, the psychological frailty and social frailty were the influencing factors for physical frailty (all P<0.05). The gender, number of multimorbidity, type of medication taken, physical frailty and social frailty were influencing factors of psychological frailty (all P<0.05). And age, number of multimorbidities, physical frailty and psychological frailty were influencing factors of social frailty (all P<0.05). A total of 3 themes were extracted through in-depth interviews, namely, "physical and psychological frailty are interrelated""physical and social frailty are interrelated", and "psychological and social frailty are interrelated". Conclusions:The physical, psychological, and social frailty in elderly patients with multimorbidity interacts with each other. Whereas the number of multimorbidities is a common risk factor for all three.

Objective:To analyze the current status, research hotspots, and development trends on the integration of primary care and prevention in China.Methods:This was a bibliometric analysis. Literature related to research on the integration of primary care and prevention in China was retrieved from CNIKI, Wanfang, VIP, Chinese Medical Journal Full Text Database, PubMed, and Web of Science for the period from January 1, 2015, to April 1, 2025. CiteSpace software was used to conduct a visual analysis of publication volume, authors and their collaborations, institutions, and keywords in the included literature.Results:A total of 292 domestic publications on the integration of primary healthcare and public health were analyzed. Research on primary healthcare-public health integration in China exhibited an overall upward trend from 2015 to 2025. Based on publication volume and temporal distribution, domestic research can be categorized into an exploratory phase (2015-2020) and a rapid development phase (2021-2025). The institutions publishing relevant research were predominantly universities and research centers, with a low institutional network density (0.013), indicating relative weak inter-institutional collaboration. The co-occurrence density among authors was 0.013 9. Collaboration predominantly occurred in small clusters, with limited cross-regional cooperation. Keywords that appeared frequently and had an intermediary centrality exceeding 0.1 included chronic diseases (0.40), public health (0.23),health management (0.18), and hypertension (0.17). Keyword clustering analysis showed that the top three categories mainly focused on public health, chronic diseases, and health management. Since 2024, emerging keywords with high burst intensity have included big data, health literacy, primary care hospitals, and infectious diseases.Conclusions:Research on the integration of medical and preventive care at the primary healthcare level in China has entered a stage of rapid development. Current research hotspots focus primarily on chronic disease management, the implementation status and barriers of primary healthcare and prevention integration models. Future research is expected to emphasize the application of intelligent technologies, and the enhancement of public health emergency response capacity.

Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P＜0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P＜0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P＜0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P＜0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P＜0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P＜0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P＜0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.