Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To explore the efficacy and adverse reactions of sacituzumab govitecan (SG) in the posterior-line therapy for advanced malignant tumors.Methods:A retrospective case series study was conducted. The clinicopathological data of 20 patients with advanced malignant tumors who were treated with SG after multiple lines of treatment in Nanjing BenQ Hospital From July to December 2023 were retrospectively analyzed. The short-term efficacy and treatment-related adverse events (TRAE) were evaluated.Results:Among the 20 patients, there were 7 males and 13 females, the median age [ M ( Q1, Q3)] was 60.0 (53.8, 72.5) years old, the median line of previous anti-tumor regimens was 4.5 (3.3, 6.0) lines, and the median duration time of SG treatment was 52.5 (35.8, 72.5) days. After SG treatment, there were 3 cases (15.0%) with partial response, including breast cancer, vaginal squamous cell carcinoma and endometrial carcinoma, 10 cases (50.0%) with stable disease and 7 cases (35.0%) with progressive disease. The objective response rate was 15.0% (3/20), and the disease control rate was 65.0% (13/20). Two cases (10.0%) were discontinued due to intolerable adverse reactions. The incidence of TRAE was 75.0% (15/20), of which the incidence of ≥grade 3 TRAE was 10.0% (2/20), including neutropenic fever and ventricular arrhythmia. Conclusions:SG has a certain therapeutic effect and controllable safety in the posterior-line therapy for advanced malignant tumors.

Objective:To compare the effect of metal prefabricated crowns and 3M350 universal resin on the dental caries of deciduous teeth.Methods:Retrospective analysis was performed on the clinical data of 89 children with proximal molar caries restoration admitted to Nantong Stomatological Hospital from January 2020 to January 2022. According to treatment methods, they were divided into observation group (metal prefabricated crowns restoration treatment, 49 cases of 49 teeth) and control group (3M350 universal resin restoration treatment, 40 cases of 40 teeth). The repair effect, occlusal function, periodontal index, treatment satisfaction and complications were compared.Results:The success rate of repair in the observation group (93.88%, 46/49) was higher than that in the control group (77.50%, 31/40), and the difference was statistically significant ( P<0.05). The maximum biting force and masticatory efficiency of the two groups after treatment were higher than those before treatment, and the observation group was higher than the control group, and the difference was statistically significant (all P<0.05). Comparison of periodontal indexes between the experimental and control groups comparison of probing depth (PD), plaque index (PLI), and bleeding index (BI) between the two groups before treatment, the differences were not statistically significant (all P>0.05); after treatment, PD, PLI, and BI were lower in both groups, and lower in the experimental group (all P<0.05). The total satisfaction of the observation group (87.76%, 43/49) was higher than that of the control group (65.00%, 26/40), and the difference was statistically significant ( P<0.05). The incidence of complications in the observation group (6.12%, 3/49) was lower than that in the control group (22.50%, 9/40), and the difference was statistically significant ( P<0.05). Conclusions:Compared with 3M350 general purpose resin, metal prefabricated crowns has better repairing effect and lower complication rate on adjacent caries of deciduous teeth, so it can be widely used in clinic.

Objective To explore the pioneering symptoms of the gastrointestinal symptom cluster and their influencing factors in gastric cancer patients with chemotherapy.Methods Based on the hospital's management system for scientific research data,463 gastric cancer patients with chemothera-py were surveyed through multicenter collaboration by the corresponding module of the MD Anderson Symptom Inventory(MDASI),the Chinese Medicine Constitution Classification and Identification Standard,and the Chinese Medicine SyndromeIdentification Standard for Gastric Cancer.IBM SPSS Statistic 22.0 and IBM SPSS Modeler 18.0 were used for data analysis.Results The first occurrence of dry mouth in the gastrointestinal symptom cluster of gastric cancer patients with chemotherapy was(22.99±10.70)hours after chemotherapy.The support,confidence,and lift for the association be-tween dry mouth and decreased appetite were 62.2％,94.8％and 1.52,respectively;for dry mouth and nausea,the numerical values were 62.2％,89.6％and 1.44;for dry mouth and vomiting,the numerical values were 62.2％,79.5％and 1.28.The results of one-way ANOVA and multivariate linear regression analysis showed that alcohol consumption,syndrome of stomach heat injuring yin,and phlegm-dampness constitution were independent influencing factors for dry mouth in gastric cancer patients with chemotherapy(P＜0.05).Conclusion Dry mouth,as a pioneering symptom of the gastroin-testinal symptom cluster,is of great significance in clinical assessment and management.Improved assessment of dry mouth can provide a basis for the construction of subsequent risk prediction model,the formulation of targeted interventions,and the enhancement of symptom management efficiency.

Objective To explore the application of Mini-CEX oriented by nurses'core competencies in the clinical teaching of intern nursing students.Methods A total of 50 students,interning in the First Affiliated Hospital of Kunming Medical University from January 1,2023 to April 30,2024,were randomly divided into experimental group and control group,with 25 students in each group.The control group was taught by traditional clinical teaching methods,and the experimental group by Mini-CEX.The data indicators of the two groups of intern nursing students were analyzed and compared at entry into and exit from the department,respectively.Results The scores of the two groups were higher than those at entry into the department(P<0.05),and the intern nursing students in the experimental group had excellent scores in nursing consultation,nursing examination,nursing diagnosis,nursing measures,humanistic care,organizational effectiveness,health consultation,and overall evaluation,and the scores were higher than those of the control group(P<0.05).The improvement in all the scores was also better than that of the control group(P<0.05).Conclusion Mini-CEX,which is oriented to the nurse'core competencies of nurses,can improve the clinical nursing abilities of intern nursing students and enhance the cultivation effect of clinical practice skills.

Objective:To compare the effect of metal prefabricated crowns and 3M350 universal resin on the dental caries of deciduous teeth.Methods:Retrospective analysis was performed on the clinical data of 89 children with proximal molar caries restoration admitted to Nantong Stomatological Hospital from January 2020 to January 2022. According to treatment methods, they were divided into observation group (metal prefabricated crowns restoration treatment, 49 cases of 49 teeth) and control group (3M350 universal resin restoration treatment, 40 cases of 40 teeth). The repair effect, occlusal function, periodontal index, treatment satisfaction and complications were compared.Results:The success rate of repair in the observation group (93.88%, 46/49) was higher than that in the control group (77.50%, 31/40), and the difference was statistically significant ( P<0.05). The maximum biting force and masticatory efficiency of the two groups after treatment were higher than those before treatment, and the observation group was higher than the control group, and the difference was statistically significant (all P<0.05). Comparison of periodontal indexes between the experimental and control groups comparison of probing depth (PD), plaque index (PLI), and bleeding index (BI) between the two groups before treatment, the differences were not statistically significant (all P>0.05); after treatment, PD, PLI, and BI were lower in both groups, and lower in the experimental group (all P<0.05). The total satisfaction of the observation group (87.76%, 43/49) was higher than that of the control group (65.00%, 26/40), and the difference was statistically significant ( P<0.05). The incidence of complications in the observation group (6.12%, 3/49) was lower than that in the control group (22.50%, 9/40), and the difference was statistically significant ( P<0.05). Conclusions:Compared with 3M350 general purpose resin, metal prefabricated crowns has better repairing effect and lower complication rate on adjacent caries of deciduous teeth, so it can be widely used in clinic.

Objective:To explore the efficacy and adverse reactions of sacituzumab govitecan (SG) in the posterior-line therapy for advanced malignant tumors.Methods:A retrospective case series study was conducted. The clinicopathological data of 20 patients with advanced malignant tumors who were treated with SG after multiple lines of treatment in Nanjing BenQ Hospital From July to December 2023 were retrospectively analyzed. The short-term efficacy and treatment-related adverse events (TRAE) were evaluated.Results:Among the 20 patients, there were 7 males and 13 females, the median age [ M ( Q1, Q3)] was 60.0 (53.8, 72.5) years old, the median line of previous anti-tumor regimens was 4.5 (3.3, 6.0) lines, and the median duration time of SG treatment was 52.5 (35.8, 72.5) days. After SG treatment, there were 3 cases (15.0%) with partial response, including breast cancer, vaginal squamous cell carcinoma and endometrial carcinoma, 10 cases (50.0%) with stable disease and 7 cases (35.0%) with progressive disease. The objective response rate was 15.0% (3/20), and the disease control rate was 65.0% (13/20). Two cases (10.0%) were discontinued due to intolerable adverse reactions. The incidence of TRAE was 75.0% (15/20), of which the incidence of ≥grade 3 TRAE was 10.0% (2/20), including neutropenic fever and ventricular arrhythmia. Conclusions:SG has a certain therapeutic effect and controllable safety in the posterior-line therapy for advanced malignant tumors.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).