ObjectiveTo evaluate the public health governance capacity in Jiangsu Province and provide an optimized pathway for the construction of a “strong, rich, beautiful, and high-quality” new Jiangsu. MethodsA total of 806 policy documents, 658 public information reports, and 148 research literatures related to public health governance capacity in Jiangsu Province from January 1995 to December 2023 were collected. The status of current public health goverance was assessed based on the evaluation criteria suitable for public health systems, and the strengths and the weaknesses of the system were identified. ResultsThe public health governance capability of Jiangsu Province was scored at 738.3 points, ranking 3rd nationally. Maternal health care and emergency response capacities achieved leading positions nationwide, both ranking 2nd. Jiangsu had exhibited a standardized guidance in the strategic level, a well-established management mechanism, an extensive coverage in information collection, and a scientifically established health targets setting. However, bottlenecks remained, including an unclear division of responsibilities across organizational departments, an insufficient public-health workforce, the absence of a stable growth mechanism for government funding investment, and difficulties in promptly identifying public needs. ConclusionJiangsu’s public-health system demonstrates leading nationally, yet several components remain underdeveloped. Future efforts should consolidate advantages while addressing weaknesses, further diversify content and forms, establish a stable funding increase mechanism, and clarify departmental functions, thereby providing solid health support for realizing the developmental goals of a “strong, rich, beautiful and high-quality” new Jiangsu.

ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

[摘 要] 目的：制备低亲和力的CD117 CAR-T细胞，探讨其对急性髓系白血病（AML）细胞Kasumi-1的体外杀伤效应。方法：调取CD117低亲和力抗体巴佐利单抗（barzolvolimab）和Fab-79D VH和VL序列，设计VH-(G4S)3-VL结构的单链抗体，分别构建带4-1BB共刺激分子的经典二代CAR分子，经基因合成后分别亚克隆至pMFG逆转录病毒载体，获得CD117-79D CAR和CD117-0159 CAR质粒。将两种CAR质粒分别包装制备逆转录病毒，检测其滴度合格后转导活化后的T细胞，构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，采用流式细胞术检测两种CAR-T细胞的阳性率。将未转导T细胞与两种CAR-T细胞分别与CD117+ Kasumi-1细胞共培养，通过流式细胞术检测Kasumi-1细胞凋亡率，以评估两种CAR-T细胞的抗肿瘤活性。结果：成功构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，其阳性率分别为（59.4 ± 2.6）%、（62.5 ± 1.2）%。未转导T细胞、CD117-79D CAR-T和CD117-0159 CAR-T细胞体外培养均能稳定增殖，且三者的增殖能力均无显著差异（均P > 0.05）。体外杀伤Kasumi-1细胞结果显示，不同效靶比条件下，CD117-79D CAR-T和 CD117-0159 CAR-T细胞较未转导T细胞展现出显著增强的杀伤能力（P < 0.05或P < 0.01），但两种CAR-T细胞的杀伤效率无显著差异（P > 0.05）。结论：成功构建低亲和力的CD117-79 CAR-T和CD117-0159 CAR-T细胞，体外实验证实其可有效杀伤CD117+ Kasumi-1细胞，为AML的靶向治疗提供了实验依据。

The sensitive scalp is a complex syndrome characterised by abnormal nerve sensations, such as stinging, itching, burning, and tightness, and diminished tolerance to physical or chemical stimuli that would not typically cause such unpleasant responses, with its pathology involving physical barrier destruction at the stratum corneum level, neural hyperreactivity and sensory nerve sensitization, and local immunological dysregulation and chronic low‑grade inflammation. The homeostasis of the scalp microenvironment plays a crucial regulatory role in maintaining the hair follicle growth cycle, yet this “soil” factor has long been underappreciated in hair loss research, which has traditionally centered on intrinsic follicular defects, such as genetic predisposition or androgen-driven mechanisms. In this review, we summarized the potential mechanisms underlying the imbalance in the “barrier-neural-immune” network in sensitive scalps. Sensitive scalp is further manifested as impaired skin barrier, including increased transepidermal water loss and abnormal lipid secretion. These alterations are accompanied by increased surface pH, excessive secretion of sebum rich in free fatty acids, reduced microbial diversity, and dysbiosis characterized by a reduction in Cutibacterium and an increase in Staphylococcus colonization. Mechanistically, we also analyzed how neurogenic inflammation, mediated by substances such as substance P (SP) and calcitonin gene-related peptide (CGRP), along with persistent low-grade inflammation, disrupts the microenvironment of the hair follicle stem cell niche through mechanisms involving mechanosensitive ion channels (e.g., Piezo1), oxidative stress, and cytokine cascades. When the barrier is compromised, the weakened stratum corneum may facilitate the penetration of external stimuli, sensitizing cutaneous nerve endings. Those hyperresponsive nerves then fire off neuropeptides like substance P and CGRP. These peptides activate mast cells and other immune cells via the MrgprB2 receptor, prompting degranulation and a wave of pro-inflammatory mediators that kick off neurogenic inflammation. At the same time, oxidative stress and inflammatory cytokines drive a persistent low-grade inflammation that directly damages the hair follicle stem cell niche. Physical compression from shrinking hair shafts activates Piezo1 channels, setting off calcium influx and Caspase‑3‑dependent apoptotic signaling. We primarily considered the interactions between inflammatory signaling and the sensitization of the androgen receptor (AR) pathway, as well as the inhibition of the Wnt/β‑catenin pathway, which may subsequently contribute to hair follicle miniaturization and disruption of the growth cycle. The inflammatory microenvironment appears to boost AR expression in dermal papilla cells, making them more sensitive to dihydrotestosterone (DHT). This heightened sensitivity may promote the expression of transforming growth factor-β1 (TGF-β1), TGF-β2, and Dickkopf-1 (DKK1), which suppress the Wnt/β‑catenin pathway—essential for follicle growth and regeneration—potentially accelerating follicular miniaturization and stalling the growth cycle. Coupled with direct inflammatory apoptosis, oxidative stress, and circadian disruption, these routes may collectively speed up hair follicle stem cell depletion and diffuse hair thinning. These findings point to the need for more mechanistic and translational research to test the proposed pathways and explore therapies that target the microenvironment in sensitive scalp-related hair loss. Ultimately, we hope to provide theoretical support for the intervention of hair loss by restoring the steady state of the scalp microenvironment and combining with new precision delivery technologies such as microneedles.

Objective:To construct a method for hepatitis B virus (HBV) DNA detection based on recombinase-mediated isothermal amplification (RAA)-clustered regularly interspaced short palindromic repeats and their associated protein 13a (CRISPR-Cas13a).Methods:Through the alignment and screening of HBV DNA sequences, a positive plasmid was constructed, and recombinase-aided amplification (RAA) primers and CRISPR RNA (crRNA) were designed. A method for detecting HBV DNA based on the RAA-CRISPR-Cas13a system was developed, and the specificity and sensitivity were evaluated. Utilizing the CRISPR-Cas13a system, 70 clinical samples from HBV DNA-positive patients with various viral loads collected at Beijing You′an Hospital from 2019 to 2021 were analyzed. The detection results were further compared with those results using real-time quantitative polymerase chain reaction (qPCR).Results:The optimal RAA amplification primers and crRNA were first screened using the RAA-CRISPR-Cas13a method, with the sensitivities for detecting HBV DNA standards and for clinical samples at 1 IU/ml and<10 IU/ml, respectively, demonstrating specificity for HBV DNA detection. Compared with qPCR (the gold standard), the detection consistency between the two methods was 100% (70/70).Conclusion:This study established a method for detecting HBV DNA by integrating recombinase-aided amplification (RAA) technology with CRISPR/Cas13a technology.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a vast and diverse family of bioactive peptides. These peptides, synthesized by ribosomes and subsequently modified by various tailoring enzymes, possess a wide chemical space. Among these modifications, radical S-adenosylmethionine (rSAM) enzymes employ unique radical chemistry to introduce a variety of novel peptide structures, which are crucial for their activity. This review examines the major types of modifications in RiPPs catalyzed by rSAM enzymes, incorporating recent advancements in protein structure analysis techniques and computational methods. Additionally, it elucidates the diverse catalytic mechanisms and substrate selectivity of these enzymes through an analysis of the latest crystal structures.
Protein Processing, Post-Translational ; S-Adenosylmethionine/chemistry* ; Ribosomes/metabolism* ; Peptides/metabolism* ; Biological Products/metabolism* ; Humans

Nanocarrier-based drug delivery systems (nDDSs) present significant opportunities for improving disease treatment, offering advantages in drug encapsulation, solubilization, stability enhancement, and optimized pharmacokinetics and biodistribution. nDDSs, comprising lipid, polymeric, protein, and inorganic nanovehicles, can be guided by or respond to biological cues for precise disease treatment and management. Equipping nanocarriers with tissue/cell-targeted ligands enables effective navigation in complex environments, while functionalization with stimuli-responsive moieties facilitates site-specific controlled release. These strategies enhance drug delivery efficiency, augment therapeutic efficacy, and reduce side effects. This article reviews recent strategies and ongoing advancements in nDDSs for targeted drug delivery and controlled release, examining lesion-targeted nanomedicines through surface modification with small molecules, peptides, antibodies, carbohydrates, or cell membranes, and controlled-release nanocarriers responding to endogenous signals such as pH, redox conditions, enzymes, or external triggers like light, temperature, and magnetism. The article also discusses perspectives on future developments.
Humans ; Drug Carriers/chemistry* ; Drug Delivery Systems/methods* ; Delayed-Action Preparations/chemistry* ; Nanoparticles/chemistry* ; Animals ; Drug Liberation ; Nanomedicine

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

Objective To explore the dual coping experience of nursing dependence among middle-aged and young patients with enterostomy and their primary caregivers from the perspective of family resilience,in order to provide evidence for improving the experience of nursing dependence and promoting family resilience.Methods Us-ing the phenomenological research method in qualitative research,18 young and middle-aged enterostomy patients and their primary caregivers were selected for semi-structured interviews with purpose sampling method,and the in-terview data were analyzed by content analysis method.Results A total of 4 themes and 8 sub-themes were ex-tracted.Theme 1:heavy dependence-elastic fatigue-weak resilience(patients avoid stomas,depression,caregivers help-lessly accepting;patients role reinforcement,excessive dependence,caregivers exhaustion);theme 2:moderate depen-dence-elastic adjustment-strong resilience trend(active exploration,mutual understanding,perceived support;focus ad-justment,mutual dependence,positive relationship);theme 3:mild dependence-elastic space-strong resilience(self-con-trollable feeling,quick adaptation,mutual growth;facing calmly,cherishing life,reshaping value);theme 4:no depen-dence-gradual loss of elasticity-weak resilience trend(refusal to seek help,self isolation,relationship cracks;frustration in seeking help,self-protection,relationship alienation).In this article,we proposed a preliminary family resilience model for patients with enterostomy.Conclusion The dual coping and family resilience of the patients with en-terostomy and their primary caregivers are different and dynamic.Family-centered support should be applied to strengthen the positive coping and improve the level of family resilience.In addition,this study also tried to pro-pose a family resilience model for patients with enterostomy based on nursing dependence,in order to enrich the connotation of family resilience.