OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective To observe the effects of different surgical approaches on the complications and tumor markers of patients undergoing radical resection of esophageal cancer.Method A prospective study was conducted on 100 patients with esophageal cancer who underwent radical surgery in our hospital from October 2019 to October 2022.They were randomly divided into an observation group and a control group using a random number table method,with 50 patients in each group,he right thoracic approach was used in the observation group and the left thoracic approach was used in the control group.Perioperative indexes,inflammatory factors[Substance P(SP),hypersensitive C-reactive protein(hs-CRP),interleukin6(IL-6)],tumor markers[cytokeratin 19 fragment antigen(CYFRA21-1),squamous cell carcinoma antigen(SCC-Ag)and carbohydrate antigen 199(CA199)]and lung function of the two groups were compared before and after surgery Indicators[vital capacity(VC),forced vital capacity(FVC),and forced expiratory volume in the first second(FEV1)]and complication rate.Result The operating time,blood loss,indwelling time,hospitalization time,and number of lymph node dissection in the observation group were(247.65±27.33)minutes,(211.82±25.49)ml,(6.97±2.12)days,(16.11±3.81)days,and(19.67±5.21),respectively,which were higher than those in the control group[(217.63±23.69)minutes,(175.67±22.13)ml,(5.43±1.80)days,(12.68±3.24)days,(15.45±4.12)](P＜0.05).On average,there was a significant increase in SP,hs CRP,and IL-6 levels in both groups 3 days after surgery(P＜0.05).The levels of SP,hs CRP,and IL-6 in the observation group were(273.96±35.45)ng/L,(11.35±2.12)mg/L,and(8.19±1.67)p.g/ml,respectively,which were lower than the control group[(298.33±38.42)ng/L,(14.29±2.68)mg/L,(10.35±1.82)pg/ml](P＜0.05);One month after surgery,there was a significant decrease in CYFRA21-1,SCC-Ag,and CA199 in both groups(P＜0.05),and in the observation group,the data of CYFRA21-1,SCC-Ag,and CA199 were(2.59±0.37)μg/L,(45.62±6.18)pg/L and(59.37±6.12)U/ml,respectively,which were lower than those in the control group[(3.12±0.43)μg/L,(60.27±7.35)pig/L,(63.28±6.49)U/ml](P＜0.05);One month after surgery,there was a significant decrease in VC,FVC,and FEV1 in both groups(P＜0.05).However,the VC,FVC,and FEV1 in the observation group were(67.21±8.69)％,(70.33±9.41)％,and(72.88±10.12)％,respectively,which were higher than those in the control group[(54.35±8.27)％,(61.65±8.79)％,(65.37±9.24)％](P＜0.05).There was no significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion Both approaches can effectively treat esophageal cancer.Among them,the right chest approach can significantly improve the effect of lymph node dissection,inhibit inflammatory reactions,reduce tumor marker levels,and have less impact on lung function,without significantly increasing the risk of complications.However,the surgical time,bleeding volume,and postoperative recovery time are relatively long.Therefore,a suitable approach should be selected in clinical practice based on the patient's actual situation.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Background Air quality health index (AQHI) is derived from exposure-response coefficients calculated from air pollution and morbidity/mortality time series, which helps to understand the overall short-term health impacts of air pollution. Objective To study the effects of common air pollutants on respiratory diseases in Urumqi and to develop an AQHI for the risk of respiratory diseases in the city. Methods The daily outpatient volume data of respiratory diseases from The First Affiliated Hospital of Xinjiang Medical University, meteorological data (daily mean temperature and daily mean relative humidity), and air pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon dioxide (CO), and ozone (O₃)] in Urumqi City, Xinjiang, China were collected from January 1, 2017 to December 31, 2021. A distributed lag nonlinear model based on quasi-Poisson distribution was constructed by time-stratified case crossover design. Adopting zero concentration of air pollutants as reference, the exposure-response coefficient (β value) was used to quantify the impact of included air pollutants on the risk of seeking medical treatment for respiratory diseases, and the AQHI was established. The association of between AQHI and the incidence of respiratory diseases and between air quality index (AQI) and the incidence of respiratory diseases was compared to evaluate the prediction effect of AQHI. Results Each 10 µg·m⁻³ increase in PM₁₀, SO₂, NO₂, and O₃ concentrations presented the highest excess risk of seeking outpatient services at 3 d cumulative lag (Lag03) and 2d cumulative lag (Lag02), with increased risks of morbidity of 0.687% (95%CI: 0.101%, 1.276%), 17.609% (95%CI: 3.253%, 33.961%), 13.344% (95%CI: 8.619%, 18.275%), and 4.921% (95%CI: 1.401%, 8.502%), respectively. There was no statistically significant PM_2.5 or CO lag effect. An AQHI was constructed based on a model containing PM₁₀, SO₂, NO₂, and O₃, and the results showed that the excess risk of respiratory disease consultation for the whole population, different genders, ages, or seasons for each inter-quartile range increase in the AQHI was higher than the corresponding value of AQI. Conclusion PM₁₀, SO₂, NO₂, and O₃ impact the number of outpatient visits for respiratory diseases in Urumqi, and the constructed AQHI for the risk of respiratory diseases in Urumqi outperforms the AQI in predicting the effect of air pollution on respiratory health.

Objective To analyze the clinical characteristics and nursing strategies of elderly patients with type 2 diabetes mellitus complicated with acute myocardial infarction(AMI).Methods A total of 138 elderly patients with type 2 diabetes mellitus combined with AMI admitted to Jiangsu Province Hospital from January 2019 to December 2021 were included in observation group,and 346 patients with AMI without diabetes mellitus were enrolled in control group.The clinical data,complications,coronary angiography results and prognosis of two groups were collected and analyzed.Results The proportion of smoking,hypertension and typical chest pain in observation group were significantly lower than those in control group,while the proportion of hyperlipidemia and Killip grade≥Ⅲ were significantly higher than those in control group(P<0.05).The proportion of patients with three branch lesions or left main trunk lesions in observation group were significantly higher than those in control group(P<0.05).The incidences of arrhythmia,acute heart failure and pulmonary infection in observation group were significantly higher than those in control group(P<0.05).There was no significant difference in the incidence of cardiogenic shock and cardiac death during hospitalization between two groups(P>0.05).Conclusion Elderly patients with type 2 diabetes mellitus complicated with AMI have atypical clinical symptoms and more complications.Early identification and active control of cardiovascular risk factors by medical staff can reduce the mortality of patients and improve the long-term prognosis.