OBJECTIVE: To explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

Tuberculosis remains a significant global public health threat.Early diagnosis and effective treatment are crucial to combat this disease.Yet,traditional diagnostic methods for tuberculosis face limitations due to their low sensitivity,extended detection periods,and dependence on sputum samples.Molecular diagnostic techniques,while offering higher sensitivity,still primarily rely on sputum samples,thereby impeding significant advancements in tuberculosis diagnosis.In clinical settings,there exists a pressing demand for diagnostic approaches that are not solely reliant on sputum samples.In recent years,extracellular vesicles(EVs),as emerging biomarkers,have demonstrated substantial potential in various diseases,including tumors and infectious diseases.A multitude of studies indicate that EVs also exhibit potential in the field of tuberculosis.This review provides an in-depth analysis of the biological characteristics of EVs and their role in the pathogenesis of tuberculosis.It systematically summarizes the progress and significance of EV-based biomarkers in tuberculosis diagnosis,treatment monitoring,and disease mechanism exploration,while addressing the challenges and future prospects in this field.The aim is to offer valuable insights and up-to-date research findings to researchers and clinicians engaged in tuberculosis-related studies.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

To analyze the transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022 and provide evidence for AIDS publicity and intervention among young students. The pol region sequences of newly reported HIV-infected students and non-student HIV-infected individuals in Nanjing City from 2016 to 2022 were collected, and the BLAST tool was used to search the published global non-Nanjing reported HIV infection sequences in the LANL HIV database. The basic molecular transmission network and regional molecular transmission network were constructed using the HIV-TRACE in a pairwise genetic distance threshold of 1.0%. 332 sequences of infected students aged≥18 years in Nanjing City, 1 904 sequences of non-student-infected individuals in Nanjing City and 1 698 non-Nanjing-infected individuals were obtained. Among the 332 infected students, the main route of infection was homosexual (96.39%), and the subtypes were CRF01_AE (37.95%), CRF07_BC (37.65%) and CRF105_0107 (10.24%). There were 890 sequences in the regional molecular transmission network, of which 21.80% were infected students in Nanjing City, 39.89% were non-student-infected individuals in Nanjing City, and 38.31% were non-Nanjing-infected individuals. In the CRF105_0107 transmission cluster, non-student-infected individuals from Nanjing accounted for 66.95% (81/121), while in the CRF07_BC transmission cluster, non-Nanjing-infected individuals accounted for 56.66% (200/353). There were 1 644 edges connected to infected students within the regional molecular transmission network, with local transmission accounting for 64.72% and regional transmission accounting for 35.28%. Regional transmission was mainly in Guangdong Province (19.83%) and other cities in Jiangsu Province (4.50%). The HIV-1 subtypes of newly reported HIV-infected students aged≥18 years in Nanjing City are mainly CRF01_AE, CRF07_BC and CRF105_0107, with local transmission as the main transmission characteristics. There is transmission between students and non-students.

Objective To investigate the risk factors for cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods Clinical data of 225 patients with RA admitted to the Second Affiliated Hospital of Zhengzhou University from January 2023 to September 2024 were collected,and the patients were divided into CVD group(n=50)and non-CVD group(n=175)according to whether they were complicated by CVD.Univariate and multivariate Logistic regression was used to analyze the risk factors of CVD in RA patients.Results Univariate Logistic regression analysis showed that age,hematocrit,red cell volume distribution width(RDW),erythrocyte sedimentation rate,neutrophil to high density lipoprotein ratio(NHR)and platelet to lymphocyte ratio(PLR)were all influencing factors for CVD in RA patients(P＜0.05).Multivariate Logistic regression analysis showed that age,RDW,NHR and PLR were all risk factors for CVD in RA patients(P＜0.05).The results of receiver operating characteristic curve analysis showed that the area under the curve(AUC)of age,RDW,NHR and PLR diagnosed CVD in RA patients were 0.844,0.797,0.572 and 0.713,respectively.The combined diagnosis AUC of four indexes was 0.898.Conclusion The risk of CVD in RA patients is influenced by many factors,and the combination of age,RDW,NHR,and PLR can improve early diagnosis of CVD in RA patients.

Objective : To investigate the correlation between the pan-immune inflammation value (PIV) and clini- cal and pathological features of primary IgA nephropathy (IgAN) ，and to evaluate the clinical significance of PIV in primary IgAN． Methods: 200 patients with primary IgAN diagnosed by renal biopsy were selected as the re- search subjects．General information，laboratory indicators，pathologic features of renal biopsy，and calculations of platelet to lymphocyte count ratio(PLR) ，neutrophil to lymphocyte count ratio(NLR) ，PIV，and other relevant in- dices about patients were collected．According to the median PIV，subjects were divided into low PIV group (PIV ≤194. 81) and high PIV group ( PIV ＞194. 81) ，and the clinical and pathological data of the two groups were compared and analyzed．Using Spearman rank correlation analysis and logistic regression analysis，the relationship between PIV and primary IgAN in terms of clinical and pathological aspects was explored． Results: There were sta- tistical significance in age，gender，height，hyperuricemia，hemoglobin，absolute neutrophil count (ANC) ，absolute monocytes count，platelet，PLR , NLR , serum uric acid，immunoglobulin G(IgG) ，immunoglobulin A(IgA) / com- plement 3 ( C3) ，and fusion degree of the podocyte foot between the two sets (P＜0. 05) ．The result of correlation analysis indicated that PIV was positively correlated with ANC，platelet，absolute monocytes count，PLR , NLR , serum creatinine，C3，serum uric acid，and fusion degree of the podocyte foot，but negatively correlated with IgG， IgA/ C3，IgA/ C4．The degree of podocyte foot process fusion was positively correlated with PIV，ANC，total choles- terol，and 24-hour urinary protein to creatinine ratio，and negatively correlated with albumin(ALB) ，IgG，IgA，and IgA/ C3．Logistic regression analysis further indicated that ALB was an independent protective factor for the occur- rence of podocyte foot process fusion in primary IgAN，and PIV was an independent risk factor for the occurrence of podocyte foot process fusion in primary IgAN． Conclusion PIV is closely related to the clinical symptoms and pathological lesions of primary IgAN．ALB is an independent protective factor for the occurrence of podocyte foot process fusion in primary IgAN，and PIV is an independent risk factor for the occurrence of podocyte foot process fu- sion in primary IgAN，which can be used as an auxiliary indicator of clinical and pathological results，providing valuable information for risk assessment and treatment plan formulation of primary IgAN．

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

With continuous advancements in the concepts of minimally invasive surgery,pancreatic surgery is gradually undergoing a transformative shift toward minimally invasive approaches.Compared with traditional open surgeries,minimally invasive procedures offer advantages such as reduced trauma,faster recovery,and fewer complications.However,due to the complex anatomical structure of the pancreas and the technical difficulties of surgical procedures,the widespread adoption of minimally invasive pancreatic surgery still faces numerous technical challenges.Currently,laparoscopic pancreaticoduodenectomy(LPD)is primarily performed in large,specialized centers with experienced teams and well-established systems.Given the high technical complexity and associated risks,reducing intraoperative risks and minimizing postoperative complications remain key focuses and major challenges in current research.This review is focused on intraoperative risk control and postoperative complication management in complex minimally invasive pancreatic surgery.We conducted a comprehensive review of recent advances in China and abroad,covering the latest progress in preoperative assessment,intraoperative procedures,complication prevention,quality management,and technological innovation.Furthermore,we discussed potential development directions in minimally invasive pancreatic surgery,including technical refinement,discipline development,procedural standardization,and multi-center collaboration.Our goal is to promote a continued progress toward more standardized,personalized,and intelligent surgical practices—ultimately benefiting a broader population of patients with pancreatic diseases.

Objective:To investigate the correlation between long-term statin use and Helicobacter pylori( Hp)infection in the elderly, and to compare the effects of rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication on lipid levels in elderly patients with mixed hyperlipidemia. Methods:A retrospective analysis was conducted on 1 181 elderly patients with hyperlipidemia, cardiovascular and cerebrovascular diseases, and peripheral arterial disease who were treated at the First Hospital of Lanzhou University between March 2019 and December 2023.According to the results of carbon 14 urea breath test(C 14-UBT), the subjects were divided into the Hp infection group and the non- Hp infection group.Multivariate logistic regression methods were used to analyze the correlation between Hp infection and statin use.A prospective case-control analysis was conducted on 109 patients with mixed hyperlipidemia and Hp infection treated during the same period, they were treated with rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication.The successful eradication people were selected as the eradication group (n=95). Patients with hyperlipidemia and Hp infection unwilling eradication was selected as the control group (n=109), and treated with rosuvastatin.Changes in lipid levels were compared over a consecutive 6-month period. Results:The overall Hp infection rate was 53.94%(637/1 181). Univariate analysis showed that the infection rate in women was higher than in men.Body mass index(BMI), low-density lipoprotein cholesterol(LDL-C), fasting blood glucose(FBG)levels in the Hp(+ )group were higher than in the Hp(-)group.Long-term low-dose aspirin users had a higher infection rate than non-users.The infection rate was lower in statin users than in non-users[42.65%(374/877) vs.55.59%(169/304), χ2=15.234, P<0.001]. Multivariate analysis showed that women had a higher infection risk than men ( OR=1.441, 95% CI: 1.102-1.729, P=0.011). Higher FBG and LDL-C levels increased the risk of Hp infection ( OR=1.406, 95% CI: 1.271-2.286, P<0.001, OR=1.118, 95% CI: 1.017-1.387, P=0.010). Aspirin use increased the risk of Hp infection( OR=1.162, 95% CI: 1.034-1.294, P=0.021), while statin use reduced the risk of Hp infection ( OR=0.177, 95% CI: 0.018-0.311, P<0.001). The Hp eradication rate was 87.16%(95/109). At 1-and 2-months post-eradication, statistically significant differences were observed between the eradication and control groups in LDL-C, total cholesterol(TC), changes from baseline, and target achievement rates(all P<0.05). At 1-month post-eradication, a statistically significant difference was observed in high-density lipoprotein cholesterol(HDL-C) levels between the two groups.Additionally, at both 1-and 2-months post-eradication, significant differences were found in the changes in HDL-C levels from baseline between the eradication group and the control group(all P<0.05). Conclusions:Long-term statin use in the elderly may reduce the risk of Hp infection.Rosuvastatin combined with a standard quadruple therapy does not improve the Hp eradication rates in elderly patients with mixed hyperlipidemia, but it facilitates short-term achievement of cholesterol targets.