Objective To investigate the risk factors associated with mortality in patients undergoing surgical treatment for myocardial infarction complicated by ventricular septal rupture, and to establish a prediction model. Methods A retrospective analysis was conducted on clinical data of patients who underwent surgical treatment of myocardial infarction with ventricular septal rupture at Beijing Anzhen Hospital from 2008 to 2022. Patients were followed up and divided into a survival group and a death group based on perioperative and follow-up outcomes. Univariate analysis was performed for all variables, followed by least absolute shrinkage and selection operator (LASSO) regression to screen risk factors affecting postoperative mortality. A Cox regression model was constructed and a Nomogram was developed. Results A total of 83 surgical patients were included, comprising 49 males and 34 females, with a mean age of (64.4±7.7) years. There were 13 perioperative deaths, and among the 70 surviving patients, 6 additional deaths occurred during follow-up. Consequently, 64 patients were assigned to the survival group and 19 to the death group. Univariate analysis revealed statistically significant differences between groups in age, culprit vessel patency status, intra-aortic balloon pump use, Killip classification, time from myocardial infarction to surgery, and time from perforation to surgery (all P<0.05). LASSO regression identified three independent predictors: age [HR=1.092, 95%CI (1.005, 1.187), P=0.039], Killip classification [HR=2.024, 95%CI (1.009, 4.059), P=0.047], and culprit vessel patency [HR=0.110, 95%CI (0.014, 0.869), P=0.036]. The Nomogram based on these variables demonstrated good discriminative ability, with area under the receiver operating characteristic curve of 0.907 at 1 month and 0.876 at 1 year postoperatively. Follow-up revealed cumulative survival rates of 78.2%, 78.2%, 74.6%, and 74.6% at 2, 5, 8, and 10 years postoperatively for all patients, and 92.7%, 92.7%, 88.5%, and 88.5% for perioperative survivors. Conclusion Patients with myocardial infarction complicated by ventricular septal rupture demonstrate favorable mid-to-long-term prognosis after surgical repair. Age, Killip classification, and culprit vessel patency are independent predictors of postoperative mortality, and the established prediction model shows satisfactory prognostic performance.

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO₂) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO₂ (ΔScvO₂) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO₂ and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO₂ (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO₂, with R² = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO₂ (R² = 0.245, p < 0.001). ΔScvO₂ had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION ΔScvO₂ served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO₂. In stable hemoglobin conditions, the absolute value of ScvO₂ could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans ; Shock, Septic/blood* ; Male ; Female ; Middle Aged ; Prospective Studies ; Oxygen Saturation ; Aged ; Fluid Therapy ; Oxygen/blood* ; Oxygen Consumption ; Adult

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To explore the efficacy and safety of sivelestat sodium in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU).Methods:Sixty patients with ARDS admitted to the ICU of the Fuyang Hospital Affiliated to Anhui Medical University from August 1, 2023 to November 1, 2024 were selected and divided into the control group (conventional treatment, 30 cases) and the sivelestat sodium group (treated with sivelestat sodium in addition to conventional treatment, 30 cases) by the random number table method. The clinical data such as inflammatory factors, blood gas analysis indicators, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score of the two groups of patients before treatment and 3 days after treatment were compared. The prognostic indicators such as mechanical ventilation time, ICU stay time, total hospital stay time, 28-day mortality rate and clinical efficacy of the two groups of patients were compared.Results:Before treatment, there were no statistically significant differences in inflammatory factors, blood gas analysis indicators, APACHE Ⅱ score and SOFA score between the two groups of patients (all P>0.05). After 3 days of treatment, the improvement degrees of APACHE Ⅱ score, SOFA score, arterial partial pressure of oxygen (PaO 2), oxygenation index (PaO 2/FiO 2), procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) in the sivelestat sodium group were all greater than those in the control group. The differences were all statistically significant (all P<0.05); The mechanical ventilation time [(5.31±4.12) d vs (7.17±2.32)d] and ICU stay [(6.31±3.42)d vs (8.93±5.26)d] of patients in the sivelestat sodium group were significantly shorter than those in the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the 28-day mortality rate between the sivelestat sodium group [20.00%(6/30)] and the control group [43.33%(13/30)] ( P>0.05). The total effective rate of treatment in the sivelestat sodium group was significantly higher than that in the control group [80.00%(24/30) vs 56.67%(17/30)], and the difference was statistically significant (χ 2=4.167, P=0.041). Conclusions:Sivelestat sodium is helpful in improving the physiological parameters of patients with ARDS, effectively reducing the levels of inflammatory factors in the body, shortening the duration of mechanical ventilation and ICU stay, but has no significant effect on the 28-day mortality rate.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Objective:To explore the efficacy and safety of sivelestat sodium in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU).Methods:Sixty patients with ARDS admitted to the ICU of the Fuyang Hospital Affiliated to Anhui Medical University from August 1, 2023 to November 1, 2024 were selected and divided into the control group (conventional treatment, 30 cases) and the sivelestat sodium group (treated with sivelestat sodium in addition to conventional treatment, 30 cases) by the random number table method. The clinical data such as inflammatory factors, blood gas analysis indicators, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score of the two groups of patients before treatment and 3 days after treatment were compared. The prognostic indicators such as mechanical ventilation time, ICU stay time, total hospital stay time, 28-day mortality rate and clinical efficacy of the two groups of patients were compared.Results:Before treatment, there were no statistically significant differences in inflammatory factors, blood gas analysis indicators, APACHE Ⅱ score and SOFA score between the two groups of patients (all P>0.05). After 3 days of treatment, the improvement degrees of APACHE Ⅱ score, SOFA score, arterial partial pressure of oxygen (PaO 2), oxygenation index (PaO 2/FiO 2), procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) in the sivelestat sodium group were all greater than those in the control group. The differences were all statistically significant (all P<0.05); The mechanical ventilation time [(5.31±4.12) d vs (7.17±2.32)d] and ICU stay [(6.31±3.42)d vs (8.93±5.26)d] of patients in the sivelestat sodium group were significantly shorter than those in the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the 28-day mortality rate between the sivelestat sodium group [20.00%(6/30)] and the control group [43.33%(13/30)] ( P>0.05). The total effective rate of treatment in the sivelestat sodium group was significantly higher than that in the control group [80.00%(24/30) vs 56.67%(17/30)], and the difference was statistically significant (χ 2=4.167, P=0.041). Conclusions:Sivelestat sodium is helpful in improving the physiological parameters of patients with ARDS, effectively reducing the levels of inflammatory factors in the body, shortening the duration of mechanical ventilation and ICU stay, but has no significant effect on the 28-day mortality rate.

Objective To investigate the effect of splenectomy on the repair of full-thickness skin tissue defects,as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.Methods According to a random number table,39 8-week-old female C57 mice were randomly divided into three groups:sham surgery group(sham group,n=13),splenectomy group with 3 days of recovery(Spx3d group,n=13),and splenectomy group with 3 weeks of recovery(Spx3w group,n=13).Full-thickness skin defects were created on the backs of the mice in each group.The wound healing conditions at different times after skin defects were observed,and the wound healing rates after the injury were calculated.Peripheral blood cell analysis was performed on day 14 after the defect,and tissue samples from the wound area were taken for hematoxylin and eosin(HE)staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate.Masson's trichrome staining was used to observe the proportion of collagen fibers.Results After splenectomy and sham surgery,the mice recovered well without significant discomfort.From 1 to 14 days after the skin defect modeling,the wound areas of the mice in all three groups gradually decreased.Compared with sham group,the wound areas were smaller in Spx3d and Spx3w groups at 3,5 and 7 days after the injury,and the differences were statistically significant(P<0.05).The wound healing rates were also significantly higher(P<0.05).Moreover,at 3 days and 5 days after the injury,the wound healing rates of Spx3d group were significantly higher than those of Spx3w group(P<0.05 or P<0.01).The peripheral blood white blood cell(WBC)count in Spx3w group was significantly higher than that in sham group and Spx3d group(P<0.01).The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group(P<0.05).Additionally,the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group(P<0.05).No statistically significant differences in red blood cell(RBC)counts were observed among the three groups(P>0.05).HE staining results showed that compared with sham group,the wound healing of the mice in Spx3d and Spx3w groups were better,and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group.At 7 days,the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group(P<0.01,P<0.05)and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group(P<0.05).At 14 days,the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group(P<0.05).The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group(P<0.05).Conclusion The healing of skin defects in mice is accelerated after splenectomy,and the recovery time after splenectomy has a certain effect on the healing of skin defects.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.