Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Crohn 's disease (CD) is an intestinal inflammatory disease of unknown etiology, the pathophysiological mechanism is still unclear. The enteric nervous system (ENS) is responsible for the autonomous regulation of intestinal function. Therefore, ENS dysfunction may be the core of the pathophysiological mechanism of CD. Here, we review the pathophysiological mechanism by which ENS contributes to the development of CD, with a focus on the role of aberrant histological manifestations of ENS and plexitis in predicting the recurrence of CD following surgery.

Objective To explore the application effect of team-based learning(TBL)teaching method combined with scenario simulation in the team-based cardiopulmonary resuscitation(CPR)training for standardized training of resident physicians in department of emergency.Methods A total of 86 standardized training resident physicians rotating in the department of emergency of Guangdong Provincial People's Hospital Southern Medical University from May 2022 to July 2023 were included as study subjects.These resident physicians were divided into a control group(n=42)and an observation group(n=44)according to different teaching methods.The control group was taught using the conventional teaching method,whereas the observation group was taught using a combination of TBL and scenario simulation-based method.The difference of theoretical assessment scores,practical skill competency and training satisfaction were compared before and after training between groups.Results The theoretical and practice skill assessment scores of both groups significantly improved after training(all P<0.05).However,there was no significant difference in the theoretical assessment scores or the score increase between the two groups before and after training.In the subcategory of theoretical assessment scores,the observation group had significantly higher points than the control group in the precautions category after training(21.09±2.07 vs.20.07±1.85,P<0.05).Compared with the control group,the observation group had significantly higher post-training practical skill scores and a significantly greater score increase(scores:86.77±3.89 vs.81.17±4.18,score increase:11±5.15 vs.8±4.60,both P<0.05).Among the subcategory practical skill scores,the observation group outperformed the control group in communication skills,emergency skills and teamwork+humanistic care(communication skills points:21.36±1.71 vs.20.07±1.54,emergency skills points:21.73±1.35 vs.20.21±1.79,teamwork+humanistic care points:22.27±1.76 vs.19.71±2.71,all P<0.05).The degree of satisfaction in overall training satisfaction,the novelty of the teaching method,teacher affinity,interests in learning,developing teamwork ability,class atmosphere,communication and expression ability,and confidence in skill mastery were significantly higher in the observation group than in the control group[overall training satisfaction:97.73%(43/44)vs.50.00%(21/42),the novelty of the teaching method:90.91%(40/44)vs.47.62%(20/42),teacher affinity:93.18%(41/44)vs.57.14%(24/42),interests in learning:97.73%(43/44)vs.59.52%(25/42),developing teamwork ability:95.45%(42/44)vs.52.38%(22/42),class atmosphere:93.18%(41/44)vs.57.14%(24/42),improve communication and expression ability:100.00%(44/44)vs.50.00%(21/42),and confidence in skill mastery:93.18%(41/44)vs.45.24%(19/42),all P<0.05].Conclusion The application of TBL teaching method combined with scenario simulation in CPR training for standardized training of resident physicians can effectively improve quality of clinical skill training.

Objective:To establish a quality and safety evaluation index system for the daytime chemotherapy in the Day Medical Management Quality Control Center of Fujian Province, providing references for objectively evaluating the quality of day chemotherapy.Methods:From December 2023 to August 2024, this study screened the initial indexes of the quality and safety evaluation index system for daytime chemotherapy through literature search and expert discussions. An index system and its weights were determined by using two rounds of Delphi method and precedence chart method. The quality of daytime chemotherapy services in 8 hospitals was evaluated by using a thousand point scale checklist based on this index system.Results:The expert motivation of both rounds of Delphi method was 100%, and the expert authority coefficient was 0.92. The quality and safety evaluation index system for daytime chemotherapy included 3 first-level indicators, 13 second-level indicators, and 54 third-level indicators; Among them, the weights of the first-level indicator included structure quality, process quality, and result quality were 0.334, 0.556, and 0.110, respectively. The quality and safety scores of daytime chemotherapy in 8 hospitals ranged from 812 to 980 points, with an average of 933 points.Conclusions:The quality and safety evaluation index system for daytime chemotherapy could objectively and comprehensively evaluate the quality and safety of hospital daytime chemotherapy.