The severity of sepsis-induced hepatic injury severely impacts disease progression and prognosis. Hence, this study investigates the role of adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSCs-exo) in mitigating hepatic injury during sepsis. An in vitro model of sepsis-induced hepatic injury was established by stimulating HepG2 cells with lipopolysaccharide (LPS). ADSCs were either co-cultured with LPS-injured HepG2 cells or used to isolate exosomes for subsequent treatment. The characteristics of ADSCs-derived exosomes were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. ADSCs-exo uptake by hepatocytes was assessed via PKH67 labeling. Cell viability, apoptosis, and lactate dehydrogenase (LDH) release were evaluated using Cell Counting Kit-8, flow cytometry, and commercial assays, respectively. The involvement of the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was further investigated. Both ADSCs and ADSCs-exo notably attenuated LPS-induced hepatocyte injury, as evidenced by lowered LDH release, enhanced cell viability, and suppressed apoptosis. ADSCs-exo were internalized by HepG2 cells. Treatment with ADSCs-exo led to a notable downregulation of phosphorylated JAK2 and STAT3. Moreover, pharmacological activation of the JAK2/STAT3 pathway partially reversed the protective effects of ADSCs-exo. Collectively, ADSCs-exo alleviate LPS-induced hepatocyte injury by inhibiting activation of the JAK2/STAT3 signaling pathway. These findings underscore the potential of ADSCs-exo as a promising cell-free therapeutic strategy for sepsis-associated liver injury.

Sepsis, a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection, exhibits profound pathobiological heterogeneity, hindering the development of effective therapies. Current subtyping approaches, often reliant on single-omics data or unsupervised clustering, yield poorly reproducible and therapeutically misaligned classifications. Here, we introduce a goal-directed subgroup identification (GD-SI) framework that optimizes patient stratification for differential treatment responses, integrating longitudinal multi-omics data (transcriptomic, proteomic, metabolomic, phenomic) from 1327 subjects across 43 hospitals. While supervised multi-omics integration frameworks (e.g., DIABLO) effectively capture shared biological signals, our approach anchors subgroup discovery directly to treatment-effect optimization. This strategy achieves substantial cross-omic concordance and, crucially, generalizes to predict differential treatment response across international critical care databases. Patients stratified by GD-SI-derived benefit scores for restrictive versus liberal fluid resuscitation exhibited marked survival differences, with similar advantages observed for ulinastatin immunomodulation. External validations in MIMIC-IV and ZiGongDB confirm prognostic generalizability. This framework reconciles biological heterogeneity with clinical actionability, offering a scalable infrastructure for precision trial design and personalized sepsis management. Our findings underscore the translational potential of omics-driven, goal-directed stratification to overcome decades of therapeutic stagnation in critical care.

Background Baseline sarcopenia has been linked to cognitive decline in older adults; however, the impact of longitudinal changes in sarcopenia status on cognitive trajectories remains unclear. Objective This aims to examine the association between 2-year transitions in sarcopenia status and subsequent 5-year cognitive trajectories among middle-aged and older adults in China. Methods We analyzed data from 8189 participants (median age 58, IQR y; n=432952.9% female) in the China Health and Retirement Longitudinal Study. Sarcopenia status was determined in 2011 and 2013 according to the 2019 Asian Working Group for Sarcopenia criteria, and participants were classified into 7 transition groups based on status changes. Cognitive function was assessed from 2013 to 2018 using standardized z scores for executive function and episodic memory. Linear mixed-effects models were applied to evaluate associations between sarcopenia transitions and cognitive trajectories, adjusting for demographic, lifestyle, and health-related covariates. Results Progression from a nonsarcopenic state was associated with greater cognitive decline compared to stable nonsarcopenia (β=–0.016, 95% CI –0.026 to –0.007; P<.001), with greater decline observed among those progressing from possible sarcopenia to sarcopenia (β=–0.027, 95% CI –0.054 to –0.001; P=.04). In contrast, regression from possible sarcopenia was associated with improved cognitive performance (β=0.028, 95% CI 0.015-0.041; P<.001). No significant improvement was observed among individuals regressing from established sarcopenia. Subgroup analyses showed consistent benefits of regression from possible sarcopenia across sex, age, residence, and education groups, except among urban residents (P=.05). Conclusions Progression in sarcopenia status was independently associated with accelerated cognitive decline, whereas regression from possible sarcopenia predicted cognitive benefit. These findings highlight possible sarcopenia as a clinically actionable and potentially reversible stage and underscore the importance of early identification and intervention to preserve cognitive health in aging populations.

BackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.MethodsThis longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.ResultsHigher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000–0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002–0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.ConclusionHigher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.

Background Lung adenocarcinoma (LUAD) has high incidence and mortality rates. Efferocytosis is involved in the progression of various cancers. The current work set out to develop a prognosis signature using efferocytosis-related genes (ERGs) for LUAD. Methods Public databases were accessed to obtain bulk and single-cell data of LUAD. Molecular subtyping of LUAD was performed using ConsensusClusterPlus, and efferocytosis-related candidate genes were screened by weighted gene co-expression network analysis (WGCNA) in combination with differential analysis. Subsequently, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to construct a prognostic RiskScore model, followed by evaluating the relationship between the RiskScore, immune infiltration, and drug sensitivity. Single-cell transcriptomic profiling of LUAD was performed with the Seurat package to elucidate the cellular origins of the key genes. The expression and potential function of the representative genes were verified by reverse transcriptional quantitative polymerase chain reaction (qPCR) (RT-qPCR), Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays. Results Two molecular subtypes of LUAD with different outcomes and clinical features were identified. Candidate ERGs were mainly enriched in inflammatory and immune-related pathways. Subsequently, seven key genes (CD200R1, BTN2A2, STAP1, DNASE2B, SAMD9, SEMA7A, BIRC3) associated with efferocytosis in LUAD were identified to establish a RiskScore model, which exhibited high robustness in predicting patient prognosis. Notably, high-risk group had lower immune scores and more unfavorable prognosis than low-risk group. Moreover, eight drugs were closely linked to the RiskScore, and low-risk group was more sensitive to Doramapimod_1042. Single-cell atlas of LUAD showed that the prognostic ERGs were mainly expressed in mast cells. In vitro experiments revealed that most of the seven ERGs were overexpressed in LUAD cells, and that SEMA7A knockdown could suppress LUAD cell proliferation, migration and invasion. Conclusions Our results provided novel insights for the prognosis prediction and personalized treatment of LUAD.

Sepsis is a life-threatening condition with high mortality, underscoring the urgent need for effective therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) analysis using plasma protein data from the FinnGen, UKB-PPP, and deCODE cohorts to identify proteins causally associated with sepsis. The analysis included 16,074 cases and 363,227 controls in FinnGen and 11,643 cases and 474,841 controls in the UK Biobank, spanning four exposure-outcome combinations. Proteins were prioritized based on a false discovery rate <0.05 in one combination and p < 0.05 in another. Colocalization and phenome-wide association studies (PheWAS) were performed to evaluate causality and potential off-target effects. Three proteins─dual specificity phosphatase 13 (DUSP13), inhibin beta C chain (INHBC), and toll-like receptor 1 (TLR1)─showed strong evidence of colocalization with sepsis risk. PheWAS confirmed broader disease associations for DUSP13 and TLR1, while INHBC showed no significant adverse associations and is considered druggable. TLR1 is currently under clinical investigation. ELISA-based experimental validation in 20 sepsis patients and 20 controls demonstrated elevated serum levels of DUSP13 and INHBC and reduced levels of TLR1 in sepsis. These findings identify DUSP13, INHBC, and TLR1 as promising therapeutic targets for sepsis, supported by genetic, phenotypic, and experimental evidence.

The relationship between possible sarcopenia and mortality remains ambiguous within Asian populations. To clarify this, we investigated the association in older adults residing in Chinese communities. Utilizing data from the China Health and Retirement Longitudinal Study, this population-based cohort study included individuals aged >= 60 years, followed from 2011 to 2012 through 2020. Possible sarcopenia was defined in accordance with the Asian Working Group on Sarcopenia 2019 criteria, and Cox proportional hazards regression was used to analyze its impact on mortality, while exploratory analyses were conducted to investigate the associations of possible sarcopenia with chronic diseases, functional independence, and hospitalization frequency. The study encompassed 5,160 participants (median age: 66 years), nearly half of whom (48.8%) were identified with possible sarcopenia. Over a 9-year follow-up period, there were 1216 recorded deaths. Analysis indicated that individuals with possible sarcopenia faced a significantly elevated mortality risk compared to their counterparts (HR: 1.79, 95% CI: 1.58-2.03; P < 0.001). Further, subgroup analyses confirmed a strong association between possible sarcopenia and all-cause mortality across various subgroups, including those related to sex, obesity status, and living environment. Additionally, exploratory analyses revealed that possible sarcopenia was significantly associated with an increased likelihood of heart disease (OR = 1.18, 95% CI: 1.03-1.34, P = 0.014) and stroke (OR = 1.41, 95% CI: 1.19-1.68, P < 0.001), as well as reduced functional independence (beta = -0.17, 95% CI: -0.24--0.10, P < 0.001). Possible sarcopenia was also associated with a higher frequency of hospitalizations at baseline (Exp(beta) = 1.50, 95% CI: 1.25-1.81, P < 0.001), although this association was no longer significant during the follow-up period. In conclusion, in Chinese community-dwelling older adults, possible sarcopenia was associated with an increased risk of all-cause mortality, several chronic diseases, and functional dependence. Thus, alleviating or preventing possible sarcopenia may improve health outcomes and extend the lifespan of these individuals.

Background: The Asian Working Group for Sarcopenia (AWGS) introduced the concept of "possible sarcopenia" in 2019. However, the association between possible sarcopenia and hip fracture is not well characterized. Hence, we conducted a study to explore this association in older Chinese adults.Methods: This was a population-based cohort study based on nationally representative data from the China Health and Retirement Longitudinal Study. Individuals aged >= 60 years with no history of hip fracture at baseline (2011-2012) were included and followed up until September 2018. Possible sarcopenia was defined based on the AWGS 2019 criteria during the study period, and the occurrence of hip fractures was monitored. The association between possible sarcopenia and hip fractures was assessed using Cox proportional hazards regression models.Results: A total of 4,011 participants were included, of whom 44.8 % had possible sarcopenia. During the 7-year follow-up, 197 individuals experienced hip fractures. Individuals with possible sarcopenia had a significantly higher risk of hip fractures than those without possible sarcopenia (hazard ratio: 2.00, 95 % confidence interval: 1.46-2.75; P < 0.001). The association was consistently observed across various subgroups based on age, sex, and overweight status.Conclusions: This study identified possible sarcopenia as a significant risk factor for hip fractures in older Chinese adults. These findings underscore the importance of addressing possible sarcopenia as a preventive measure to reduce the incidence of hip fractures.

The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine Noxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor beta 1 (TGF-beta 1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE(- /-) mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAOinduced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-beta 1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2 alpha-ATF4-CHOP or the PERk-eIF2 alpha-ATF3-TGF-beta signalling pathways.

Background:Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods:We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results:The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions:Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

The prevention and control of human immunodeficiency virus and sexually transmitted infections (HIV/STI) face challenges worldwide, especially in China. Prediction tools, which analyze medical data and information to make future predictions, were once mainly used in HIV/STI research to help make diagnostic or prognostic decisions, has have now extended to the public as a freely accessible tool. This article provides an overview of the different roles of prediction tools in preventing and controlling HIV/STI from the perspectives of individuals, healthcare providers, and policymakers. For individuals, prediction tools serve as a risk assessment solution that assess their risk and consciously improve risk reception or change risky behaviors. For researchers, prediction tools are powerful for assisting in identifying risk factors and predicting patients’ infection risk, which can inform timely and accurate intervention planning in the future. In order to achieve the best performance, current research increasingly underscores the necessity of considering multiple levels of information, such as socio-behavioral data, in developing a robust prediction tool. In addition, it is also crucial to conduct trials in clinical settings to validate the effectiveness of prediction tools. Many studies only use theoretical parameters such as model accuracy to estimate its predictive. If these improvements are made, the application of prediction tools could be a potentially inspiring solution in the prevention and control of HIV/STI, and an opportunity for achieving the World Health Organization’s agenda to end the HIV/STI epidemic by 2030.

Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1

目的 探讨坎地沙坦改善血管紧张素Ⅱ导致的内皮损伤的机制.方法 (1)先用血管紧张素Ⅱ(AngⅡ)干预培养人脐静脉内皮细胞(HUVEC)构建氧化应激细胞株,再用氯沙坦或坎地沙坦对氧化应激的细胞株进行干预,最后用WB法检测eNOS、P-eNOS内皮功能蛋白,P38/P-P38、NF-KB/P-NF-KB炎症通路蛋白及血管紧张素转化酶2(ACE2)蛋白的表达情况.(2)先用AngⅡ和坎地沙坦干预HUVEC细胞构建模型细胞株,再用ACE2的小干扰RNA(siRNA)和ACE2激动剂(DIZE)干预模型细胞株,最后用WB法检测ACE2蛋白,P38/NF-KB通路中P-P38和P-NF-KB蛋白的表达情况.结果 (1)氯沙坦或坎地沙坦干预后,坎地沙坦组和氯沙坦组的P-eNOS蛋白较AngⅡ组的表达含量上升;坎地沙坦组和氯沙坦组P-P38及P-NF-KB的蛋白表达含量较AngⅡ干预组下降,且坎地沙坦组的下降趋势更加明显.(2)予DIZE干预后,HUVECs的ACE2蛋白表达升高,P-NF-KB蛋白的表达下降;予ACE2小干扰RNA干预后,HUVECs的ACE2表达下降;P-NF-KB蛋白的表达上升.结论 坎地沙坦除了可以通过拮抗AngⅡ的受体通路阻断P38/NF-KB炎症通路表达保护内皮细胞功能之外,还可以通过促进内皮细胞分泌ACE2抑制NF-KB炎症通路从而起到保护内皮细胞的作用.

ObjectiveThe aim of this study was to retrospectively explore the relationship between serum sodium and in-hospital mortality and related factors in critically ill patients with spontaneous subarachnoid hemorrhage (SAH).MethodsData were collected from the Medical Information Mart for Intensive Care IV database. Restricted cubic splines were used to explore the relationship between serum sodium and in-hospital mortality. Receiver operating characteristic analysis was used to calculate the optimal cutoff value of sodium fluctuation, and decision curve analysis was plotted to show the net benefit of different models containing serum sodium.ResultsA total of 295 patients with spontaneous SAH were included in the retrospective analysis. The level of sodium on ICU admission and minimum sodium in the ICU had a statistically significant non-linear relationship with in-hospital mortality (non-linear P-value < 0.05, total P-value < 0.001). Serum sodium on ICU admission, minimum serum sodium during ICU, and sodium fluctuation were independently associated with in-hospital mortality with odds ratios being 1.23 (95% confidence interval (CI): 1.04–1.45, P = 0.013), 1.35 (95% CI: 1.18-1.55, P < 0.001), and 1.07 (95% CI: 1.00–1.14, P = 0.047), respectively. The optimal cutoff point was 8.5 mmol/L to identify in-hospital death of patients with spontaneous SAH with sodium fluctuation, with an AUC of 0.659 (95% CI 0.573-0.744).ConclusionAmong patients with spontaneous SAH, we found a J-shaped association between serum sodium on ICU admission and minimum sodium values during ICU with in-hospital mortality. Sodium fluctuation above 8.5 mmol/L was independently associated with in-hospital mortality. These results require being tested in prospective trials.

OBJECTIVE:To compare the predictive value of Oxford acute severity of illness score (OASIS) and simplified acute physiology score II (SAPS II) for in-hospital mortality in intensive care unit (ICU) patients with sepsis. METHODS:A retrospective cohort study was conducted using the data in the Medical Information Mart for Intensive Care-IV 0.4 (MIMIC-IV 0.4). Based on Sepsis-3 diagnostic criteria, the basic information of ICU adult sepsis patients with infection and sequential organ failure assessment (SOFA) score ≥ 2 within 24 hours of ICU admission admitted for the first time in the database was extracted, including gender, age, vasopressor drugs, sedative drugs, mechanical ventilation, renal replacement therapy, length of ICU stay, OASIS, SAPS II scores, etc. The primary outcome was in-hospital mortality. A receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to compare the prognostic value of OASIS score and SAPS II score. RESULTS:A total of 11 098 adult ICU sepsis patients were enrolled in the final analysis, of which 2 320 died and 8 778 survived in hospital, with a mortality of 20.90%. Compared with the survivors, the non-survivors were older [years old: 71 (60, 81) vs. 67 (56, 78)], had longer length of ICU stay [days: 6.95 (3.39, 13.07) vs. 4.23 (2.19, 9.73)] and higher proportions of using vasopressor drugs, sedative drugs, mechanical ventilation and renal replacement therapy [vasopressor drugs: 50.65% (1 175/2 320) vs. 33.05% (2 901/8 778), sedative drugs: 58.53% (1 358/2 320) vs. 48.41% (4 249/8 778), mechanical ventilation: 89.57% (2 078/2 320) vs. 81.66% (7 168/8 778), renal replacement therapy: 11.98% (278/2 320) vs. 6.57% (577/8 778), all P < 0.01]. Moreover, the non-survivors had higher OASIS score [43 (36, 49) vs. 35 (29, 41), P < 0.01] and SAPS II score [49 (40, 60) vs. 38 (31, 47), P < 0.01] as compared with the survivors. ROC curve analysis showed that the AUC of OASIS score and SAPS II score for predicting in-hospital death of ICU patients with sepsis was 0.713 [95% confidence interval (95%CI) was 0.701-0.725] and 0.716 (95%CI was 0.704-0.728), respectively, and the Delong test showed no significant difference in AUC between the two scoring systems (P > 0.05). CONCLUSIONS:OASIS score has a good predictive value for in-hospital mortality in sepsis patients, which is similar to SAPS II score. OASIS score is simpler and has a broader clinical application prospect than SAPS II score.

Atherosclerosis, the pathophysiological basis of most malignant cardiovascular diseases, remains a global concern. Transcription factors play a key role in regulating cell function and disease progression in developmental signaling pathways involved in atherosclerosis. Activated transcription factor (ATF) 3 is an adaptive response gene in the ATF/cAMP response element binding (CREB) protein family that acts as a transcription suppressor or activator by forming homodimers or heterodimers with other ATF/CREB members. Appropriate ATF3 expression is vital for normal physiological cell function. Notably, ATF3 exhibits distinct roles in vascular endothelial cells, macrophages, and the liver, which will also be described in detail. This review provides a new perspective for atherosclerosis therapy by summarizing the mechanism of ATF3 in atherosclerosis, as well as the structure and pathophysiological properties of ATF3. KEY MESSAGES: • In endothelial cells, ATF3 overexpression aggravates oxidative stress and inflammation. • In macrophages and liver cells, ATF3 can act as a negative regulator of inflammation and promote cholesterol metabolism. • ATF3 can be used as a potential therapeutic factor in the treatment of atherosclerosis.

目的 应用加权发病率综合征联合抗菌药物算法(WISCA)分析胆道感染(BTI)病原菌分布和耐药情况.方法 收集宁波市医疗中心李惠利医院2015年1月1日至2020年9月30日首次送检结果阳性的934例BTI患者的胆汁,标本培养分离后得到病原菌1251株,采用法国生物梅里埃公司的VITEK-2 Compact进行细菌鉴定及药物敏感试验,统计分析细菌分布及耐药率,再应用WISCA计算各药物的加权敏感性.结果 1251株病原菌中革兰阴性杆菌812株(64.9％),革兰阳性球菌363株(29.0％),真菌76株(6.1％);革兰阴性杆菌中位列前4位的是大肠埃希菌(31.3％)、肺炎克雷伯菌(10.6％)、铜绿假单胞菌(4.2％)、阴沟肠杆菌(3.8％);革兰阳性球菌中位列前4位的是粪肠球菌(10.1％)、鹑鸡肠球菌(4.4％)、铅黄肠球菌(4.3％)、鸟肠球菌(2.6％);最常见的真菌是白假丝酵母(3.4％)、光滑假丝酵母(2.1％).大肠埃希菌和肺炎克雷伯菌对三代头孢菌素的耐药率以头孢曲松最高,分别是68.2％和33.6％,对左氧氟沙星的耐药率分别为54.0％和24.4％,对亚胺培南的耐药率为1.5％和6.1％;铜绿假单胞菌对头孢哌酮/舒巴坦、哌拉西林他唑巴坦和亚胺培南的耐药率分别为16.7％、22.0％和42.3％;鹑鸡肠球菌和铅黄肠球菌对万古霉素耐药率分别为86.4％和91.7％.抗菌药物中对革兰阴性杆菌加权敏感性超过80.0％有阿米卡星(93.0％)、亚胺培南(83.0％);对革兰阳性球菌加权敏感性超过80.0％有替加环素(81.0％)、青霉素(80.2％);对真菌加权敏感性超过80.0％有两性霉素B(100.0％)、伏立康唑(86.8％)、氟康唑(82.9％);联合治疗加权敏感性超过80.0％的有亚胺培南联合替加环素(83.2％)、厄他培南联合环丙沙星(82.5％)、哌拉西林他唑巴坦联合环丙沙星(81.9％)、哌拉西林他唑巴坦联合替加环素(80.9％)、亚胺培南联合利奈唑胺(80.0％).结论 亚胺培南仍是胆道感染经验性用药的良好选择,替加环素可作为联合用药首选.

目的 比较序贯器官衰竭评分(SOFA)、牛津急性疾病严重程度评分(OASIS)和简化急性生理学评分(SAPS)II预测ICU患者院内死亡的价值,以期为临床选择疾病严重程度评分系统提供理论证据.方法 提取重症监护医学信息数据库IV(MIMIC-IV)中成年ICU患者的基本信息、SOFA、OASIS、SAPSⅡ等,以院内死亡为主要结局指标,采用多因素logistic回归评价各评分是否是院内死亡的独立危险因素;绘制ROC曲线,计算并比较AUC的差异以评价各评分系统对预后的预测效能.结果 共纳入52184例ICU成年患者,其中存活组46597例,死亡组5587例,院内死亡率为10.71％.与存活组比较,死亡组患者3种评分分值均高(均P<0.01).多因素logistic回归分析显示,SOFA(OR=1.330,95％CI:1.315～1.344,P<0.001)、OASIS评分(OR=1.117,95％CI:1.112～1.122,P<0.001)和SAPSⅡ(OR=1.063,95％CI:1.061～1.066,P<0.001)均是院内死亡的独立危险因素.ROC曲线分析显示SOFA、OASIS和SAPSⅡ3种的AUC分别为0.768(95％CI:0.762～0.775)、0.776(95％CI:0.770～0.783)和0.775(95％CI:0.768～0.781),Delong检验显示SAPSⅡ和OASIS的AUC值比较差异无统计学意义(P>0.05),但两者均优于SOFA(均P<0.05).结论 SOFA、OASIS和SAPSⅡ对ICU患者院内死亡都具有良好的预测价值,但SAPSⅡ和OASIS的预测价值优于SOFA,更加简便的OASIS可能有更广阔的临床应用前景.

Objective: There is a paucity of published data to evaluate the efficacy and safety of imipenem (IPM) and piperacillin-tazobactam (PT) dosing regimens in the treatment of septic patients acquiring continuous renal replacement therapy (CRRT). Methods and Materials: Critically-ill patients were grouped into short-stay and long-stay intensive care unit (ICU) patients. Pathogens were isolated from bloodstream infections in these patients. Minimum inhibitory concentration (MIC) value was determined by agar dilution method. Population PK models were introduced in this study, and differences in the likelihood of achieving efficacious and toxic exposures of IPM and PT for critically-ill patients were assessed. Results: A total of 86 K. pneumoniae bloodstream infection associated isolates were collected, and the MIC50 and MIC90 for short-stay ICU patients were 0.5/4 mg/L and 32/128 mg/L, respectively. IMP 0.5g q8h reached 90% probability of target attainment (PTA) against isolates with MICs <= 2 mg/L and was recommended to empirically treat short-stay ICU patients during CRRT based on the target of 40% integral T>MIC. However, based on a more aggressive target of 100% integral T>MIC, all the simulated IMP regimens except for IMP 1g q6h failed to achieve >80% cumulative fraction of response (CFR) in such patients. Unfortunately, the risk of drug-related toxicity for IMP 1g q6h was relatively high (50-85%). For PT, even the regimen of 4/0.5g q6h failed to provide sufficient antimicrobial exposure in short-stay ICU patients acquiring CRRT. Conclusion: No dose adjustment was required for the conventional IMP and PT regimens in the critically-ill population acquiring CRRT. Empirical treatment of IMP 0.5g q8h/q6h, not for PT, may provide sufficient antimicrobial exposure for short-stay ICU patients during CRRT. PT should be used in the knowledge of MIC results.

This study aimed to investigate the prevalence of T2DM and its risk factors in rural areas in Yinzhou District of Ningbo, China. A cross-sectional study with 4832 participants aged 18 years or older was conducted during the period of March 2013 to May 2013. Among the participants, 4760 completed a self-administered survey and physical examinations. Data collected included demographic characteristics, lifestyle, medical history, anthropometric measurements, and clinical assessment. After an overnight fasting of at least 10 h, participants also underwent an oral glucose tolerance test (OGTT) for diagnosing T2DM. Logistic regression analysis was performed to determine the risk factors associated with T2DM. The area under the receiver operating characteristic curve (AUROC) was used to assess the prediction ability of the models. The age-standardized prevalence of T2DM was 7.86% (95% confidence interval (95% CI = 7.10–8.62%), and the crude prevalence was 15.36%. In multivariate logistic regression models, age (≥ 65), obesity, and hypertension were the common risk factors of T2DM for both males and females. The AUROC of the T2DM model was 0.735 (95% CI = 0.709–0.762), indicating the accuracy of the model in predicting T2DM. Old age, obesity, hypertension, and elevated triglycerides and LDL-C were the risk factors for T2DM. And the predictive power of ROC curve we established for predicting T2DM had a good accuracy. Therefore, diabetes health education and early screening programs should be developed and strengthened for the prevention of T2DM in rural areas.