OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

Objective To analyze the overall characteristics, research hotspots, and development trends of immune cell-related studies in radiotherapy for rectal cancer. Methods A systematic search was conducted by using Web of Science Core Collection to retrieve articles related to radiation therapy and immune cells in rectal cancer published from 1991 to 2024. Advanced bibliometric tools, such as VOSviewer and CiteSpace, were utilized to facilitate analysis and describe publication trends, geographic contributions, institutional affiliations, journal prominence, author collaboration, and prominent keywords. Results The annual number of relevant publications has increased steadily, showing remarkable growth over the past five years. Studies focusing on adaptive immune cells (T and B cells) account for the largest proportion of works and form the most extensive collaboration networks, reflecting the central role of T cell–mediated antitumor immunity in radiotherapy. Meanwhile, innate immune cells, including myeloid-derived suppressor cells, macrophages, monocytes, and neutrophils, are increasingly investigated for their regulatory roles in shaping the tumor immune microenvironment and influencing therapeutic responses. Among countries, China and the United States have contributed the highest number of publications and demonstrated strong academic influence. While several stable research groups have been formed, intergroup collaboration remains limited. Keyword analysis revealed that radiotherapy-induced immune modulation, tumor immune microenvironment remodeling, and treatment response have emerged as major research hotspots. Conclusion Research on immune cells in rectal cancer radiotherapy has progressed rapidly in recent years. The emphasis of this field has gradually shifted from single-treatment approaches to mechanistic studies investigating the interaction between radiotherapy and the tumor immune microenvironment. The field still demonstrates considerable potential for future research and clinical translational applications.

This paper summarized professor ZHANG Boli's experience in syndrome differentiation and treatment of metabolic syndrome （MetS） based on the theory of "diseases related to damp， turbidity， phlegm， and rheum". It is considered that damp， turbidity， phlegm， and rheum are the key pathological factors in the onset of MetS. The core pathogenesis of this disease includes the failure of the liver to govern the free flow of qi， the depletion of spleen and kidney， and the accumulation and impairment caused by damp， turbidity， phlegm， and rheum. It is important to emphasize early intervention， sequential treatment， and thorough elimination of pathogenic factors. The treatment takes fortifying the spleen and promoting middle jiao （焦）， soothing the liver and regulating qi， and tonifying the kidney to restore transformation as the fundamental principles. Furthermore， targeted treatments are implemented according to the evolution of damp， turbidity， phlegm， and rheum， including treating damp early， examining the tongue coating to eliminate turbidity， differentiating and treating concurrent phlegm， and applying warm dredging moderately. At the same time， specific medicinals are combined based on abnormal indicators such as blood glucose， blood lipids， blood pressure， and uric acid， aiming to address both root causes and symptoms simultaneously.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objective: To analyze the status of wasting among primary and secondary school students in Guangxi from 2021 to 2025, to explore the factors associated with wasting, so as to provide scientific evidence for improving student s nutrition. Methods: Based on the National Surveillance and Intervention Program on Common Diseases and Health Risk Factors among Students, a stratified cluster random sampling was adopted from 2021 to 2025 to recruit 71 077, 236 511, 243 466, 249 619 and 246 259 primary and secondary school students in Guangxi for physical examination and questionnaire survey. The χ 2 test was used for intergroup comparisons. Chi-square trend test was used to conduct trend analysis. Multilevel Logistic regression model was employed to identify factors associated with wasting. Results: The overall wasting detection rate was 11.65% during 2021-2025. Over the five year period, the rate exhibited a S shaped fluctuation pattern characterized by "decline-rise-decline" and the difference across years was statistically significant ( χ 2=230.53, P <0.05). Multilevel Logistic regression analysis showed that male students ( OR = 1.63 ), primary school students ( OR =1.53) and junior high school students ( OR =1.12), boarding students ( OR =1.08), and students with adequate sleep duration ( OR =1.12) were positively correlated with the risk of wasting (all P <0.05). Students who consumed sugar sweetened beverages ≥1 time/day ( OR =0.93), ate fresh fruit ≥1 time/day ( OR =0.95), had moderate to vigorous physical activity for more than 60 minutes per day ( OR =0.88), and had moderate to vigorous physical activity for more than 60 minutes per day on more than half of weekend days ( OR =0.88) were negatively correlated with the risk of wasting (all P <0.05). Conclusions Wasting status among primary and secondary school students in Guangxi improved between 2021 and 2025, though fluctuations persisted. Greater attention should be paid to the nutritional status of male students and boarding students. While cultivating balanced dietary habits and appropriate exercise behaviors, the complex relationship between sleep and malnutrition should also be given due consideration.

Objective To investigate the correlation and diagnostic value of C-X3-C motif chemokine ligand 1(CX3CL1)and C-C motif chemokine ligand 5(CCL5)in peripheral blood with NOD-like receptor thermal protein domain associated protein 3(NLRP3)mRNA expression,interleukin(IL)-1β,IL-18 and T regulatory cells(Treg)/T helper cells 17(Th17)ratio imbalance in allergic rhinitis(AR)patients.Methods A total of 143 patients with AR admitted to the hospital from January to October 2023 were selected as the AR group,and another 143 healthy volunteers who underwent physical examinations in the hospital during the same peri-od were selected as the control group.The AR group was divided into the moderate-to-severe AR group and the mild AR group according to the severity of AR.Pearson and Spearman correlation analyses were used to analyze the correlations between the expressions of CX3CL1 and CCL5 in the peripheral blood of AR patients and NLRP3 mRNA,as well as serum IL-1β,IL-18,Treg,Th17,and the ratio of Treg/Th17.Univariate analy-sis and multivariate Logistic regression were used to analyze the influencing factors of AR,and the receiver op-erating characteristic(ROC)curve was used to analyze the diagnostic value of peripheral blood CX3CL1,CCL5,NLRP3 mRNA,and the ratio of Treg/Th17 for AR.Results Compared with the control group,the levels of CX3CL1 and CCL5 in the peripheral blood of the mild AR group and the moderate to severe AR group increased,and the difference was statistically significant(P＜0.05).The proportions of IL-1β,IL-18,Th17 cells and the expression of NLRP3 mRNA in the moderate to severe AR group were higher than those in the mild AR group,while the proportion of Treg cells and the ratio of Treg/Th17 were lower than those in the mild AR group,and the differences were statistically significant(P＜0.05).CX3CL1 and CCL5 were positive-ly correlated with the proportions of IL-1β,IL-18,Th17 cells and the expression of NLRP3 mRNA,and nega-tively correlated with the proportion of Treg cells and the ratio of Treg/Th17(P＜0.05).Compared with the control group,the proportion of family history of AR,total immunoglobulin E,the proportion of dust exposure to residence or occupation,the proportions of CX3CL1,CCL5,IL-1β,IL-18,Th17 cells and the expression of NLRP3 mRNA in the AR group increased,while the proportion of Treg cells and the ratio of Treg/Th17 de-creased,the difference was statistically significant(P＜0.05).The results of multivariate Logistic regression analysis showed that family history of AR,exposure to dust in residence or occupation,NLRP3 mRNA,CX3CL1,and CCL5 were independent risk factors for the onset of AR,and the ratio of Treg/Th17 was an in-dependent protective factor(P＜0.05).The results of ROC curve analysis showed that the area under the curve of the four combined diagnoses of peripheral blood CX3CL1,CCL5,NLRP3 mRNA,and the ratio of Treg/Th17 for AR was 0.945.They were greater than 0.808,0.790,0.800,and 0.797 of CX3CL1,CCL5,NL-RP3 mRNA,and the ratio of Treg/Th17 in peripheral blood diagnosed separately(Z=6.245,5.715,5.881,5.347,P＜0.001).Conclusion The elevated levels of CX3CL1 and CCL5 in peripheral blood are related to the severity of AR.Both may be involved in the occurrence and development of AR by regulating the NLRP3 in-flammasome and the imbalance of the Treg/Th17 ratio.The combined detection of CX3CL1,CCL5,NLRP3 mRNA and the ratio of Treg/Th17 has certain diagnostic value for AR.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVES: To investigate the core targets and immunomodulatory mechanisms of Huoluo Xiaoling Pellet (HLXLP) for promoting tissue repair. METHODS: Network pharmacology and protein-protein interaction network were used to screen active components in HLXLP, the disease-related targets and the core targets, followed by GO and KEGG enrichment analyses and molecular docking to predict the pharmacological mechanisms. The toxicity of HLXLP was evaluated in zebrafish, and in a tissue regeneration model established in 3 dpf zebrafish larvae by amputating 95% of the tail fin, the effects of a formulated zebrafish embryo culture medium and 10, 20, and 40 μg/mL of aqueous extract of HLXLP on tissue regeneration was evaluated; RT-qPCR was performed to detect mRNA expressions of tissue regeneration marker genes and the core target genes. Transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to observe immune cell migration during tissue regeneration, and macrophage polarization at different stages was assessed with RT-qPCR. RESULTS: We identified a total of 149 intersected targets between HLXLP active components and tissue repair and 5 core targets (AKT1, IL-6, TNF-α, EGFR and STAT3). GO and KEGG analyses suggested that the effects of HLXLP were mediated primarily through the JAK-STAT pathway, adhesion junctions and positive regulation of cell migration. HLXLP was minimally toxic below 40 μg/mL and lethal at 320 μg/mL in zebrafish, and caused renal and pericardial edema and vascular defects above 80 μg/mL. In zebrafish with tail fin amputation, HLXLP significantly promoted tissue regeneration, reduced IL-6 and TNF-α and enhanced AKT1, EGFR and STAT3 mRNA expressions, modulated neutrophil and macrophage recruitment to the injury sites, and regulated M1/M2 macrophage polarization during tissue regeneration. CONCLUSIONS HLXLP promotes zebrafish tail fin regeneration through multiple active components, targets and pathways for immunomodulation of immune cell migration and macrophage polarization to suppress inflammation and accelerate healing.
Animals ; Zebrafish/physiology* ; Animal Fins/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Regeneration/drug effects* ; Network Pharmacology ; Signal Transduction ; Macrophages

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic