OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

ObjectiveTo investigate the role of serum HBV RNA in assessing antiviral therapy for patients with chronic hepatitis B， as well as its potential as a biomarker in clinical therapy， and to provide a scientific basis for the clinical treatment of chronic hepatitis B. MethodsA total of 134 patients who were diagnosed with chronic HBV infection in The Second Affiliated Hospital of Kunming Medical University from April 2023 to May 2024 were enrolled as subjects， and related examinations were performed， including HBV DNA， serum HBV RNA， liver function， HBsAg， anti-HBs， HBeAg， anti-HBe， anti-HBc， and transient elastography of the liver. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test or the continuity-adjusted chi-square test was used for comparison of categorical data between two groups. Pearson correlation analysis or Spearman correlation analysis was performed. ResultsThe 134 patients with chronic HBV infection were divided into HBeAg-positive group with 45 patients and HBeAg-negative group with 89 patients， and there were significant differences between the two groups in age， the positive rate and quantitative value of HBV DNA， the positive rate and quantitative value of serum HBV RNA， HBsAg， anti-HBe， and ALT （all P<0.05）. In the cohort study of the HBeAg negative group， there were significant differences in the levels of HBV DNA， HBsAg， and GGT between the serum HBV RNA-negative group with 14 patients and the serum HBV RNA-positive group with 75 patients （all P<0.05）. There were 28 patients in the HBeAg-positive group and 62 in the HBeAg-positive group who used antiviral drugs for ≥1 month， and the 28 HBeAg-positive patients had an HBV RNA positive rate of 100%， while for the 62 HBeAg-negative patients， there were significant differences in the positive rate and level of serum HBV RNA between the patients with different durations of medication （both P<0.05）. Among the 89 HBeAg-negative patients， there were 62 treatment-experienced patients and 27 treatment-naïve patients， and there was a significant difference between the two groups in HBV RNA level ［2.07 （1.52 — 2.82） log₁₀ copies/mL vs 2.69 （1.80 — 3.55） log₁₀ copies/mL， Z=2.034， P=0.042］. For HBeAg-negative patients， serum HBV RNA was positively correlated with HBV DNA and HBsAg （both P<0.05）， and for HBeAg-positive patients， serum HBV RNA was significantly positively correlated with HBV DNA， HBsAg， and HBeAg （all P<0.05）. ConclusionAntiviral therapy can reduce viral load， and for HBeAg-negative patients with high-sensitivity HBV DNA below the lower limit of detection， serum HBV RNA can fill the “gap” in the detection of viral replication.

Objective To investigate the current status of knowledge,attitude,and practice(KAP)re-garding the clinical application of graduated compression stockings(GCS)for preventing venous thromboem-bolism(VTE)among medical staff and analyze its influencing factors.Methods Through convenience sam-pling,5 706 medical staff from 85 hospitals in Chongqing were surveyed using the"Questionnaire on KAP of Clinical Application of GCS for VTE Prevention"between March 16 and 30,2024.Univariate and multiple lin-ear stepwise regression analyses were conducted to explore influencing factors.Results The scores for knowl-edge,attitude,and practice in the clinical application of GCS for VTE prevention among healthcare workers were(37.77±10.56),(16.85±3.05),and(24.85±7.51),respectively.Age,highest education level,seniori-ty,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombosis prevention center certification,and GCS procurement channels were influen-cing factors for knowledge scores.Professional title,whether they had received GCS application training,hos-pital level,and whether the hospital passed the national venous thrombosis prevention center certification were influencing factors for attitude scores.Gender,age,highest education level,seniority,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombo-sis prevention center certification,and GCS procurement channels were influencing factors for behavior scores.Conclusion Healthcare workers'knowledge of clinical application of GCS for VTE prevention is at a medium level,their attitude toward clinical application is positive,and practical behaviors are basically in compliance with standards.Hospital managers should emphasize training and assessment on clinical application of GCS for healthcare workers,strengthen quality control in practical implementation,and ensure patients receive stand-ardized mechanical VTE prevention.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

Objective To analyze the distribution characteristics and trends of occupational exposure types of medical radiation workers in Gansu Province, China, and to provide a basis for administrative departments to formulate and adjust radiation protection policies. Methods According to the radiation health information platform, the data of occupational exposure types of radiation workers in Gansu Province from 2014 to 2023 were obtained. The proportions of occupational exposure types in each physical examination year was statistically analyzed. Results From 2014 to 2023, the number of medical radiation workers accounted for more than 70% of the total number of radiation workers. The proportion of X-ray imaging diagnostic radiation workers in the total number of medical radiation workers gradually decreased but remained the highest, exceeding 68% annually. The proportion of interventional radiology workers in the total number of medical radiation workers increased from 13.8% to 25.5%. The proportions of radiation therapy and nuclear medicine workers in the total number of medical radiation workers increased slowly. The numbers of interventional radiology and radiotherapy workers in tertiary hospitals both accounted for more than 70% of the total number of such workers in the province. The proportion of interventional radiology workers increased and then decreased. The proportion of radiotherapy workers increased significantly from 70.5% to 93.0%. The number of nuclear medicine workers in tertiary hospitals accounted for more than 80% of such workers in the province. Conclusion Radiation protection policies and measures should be adjusted according to the changes in the types of occupational exposure. The focus of these policies and measures should differ depending on the level of healthcare institutions, the type of radiological diagnostic and therapeutic services, and the characteristics of various occupational exposure types .

Objective: To investigate the epidemiological characteristics of pulmonary tuberculosis (PTB) among residents aged 60 years and older in Yangzhou City, Jiangsu Province from 2013 to 2022, so as to provide the evidence for the improvement of PTB prevention and control measures in this population. Methods: Data of PTB cases aged 60 years and older in Yangzhou City from 2013 to 2022 were collected from the Chinese Disease Prevention and Control Information System. The temporal, population, and regional distribution characteristics of PTB cases were analyzed using the descriptive epidemiological method. Results: A total of 8 726 PTB cases aged 60 years and older were registered in Yangzhou City from 2013 to 2022, including 4 167 cases positive for pathogenic tests, with a positive rate of 47.75%. The registered incidence rates and the positive rates of pathogenic tests of PTB among residents aged 60 years and older in Yangzhou City showed downward trends from 2013 to 2022 (both P<0.05). The average annual registered incidence rate of PTB was 83.95/105, and the average annual registered incidence rate of PTB positive for pathogenic tests was 40.09/105. The average annual registered incidence rate of PTB in males was higher than that in females (138.57/105 vs. 31.76/105, P<0.05). The registered incidence rate of PTB showed an increasing trend with age (P<0.05), with the highest rate observed in the age group of 75-<80 years (110.37/105). The top three regions with the highest average annual registered incidence rates of PTB were Jiangdu District (94.34/105), Baoying County (91.61/105) and Hanjiang District (84.93/105). Conclusions The registered incidence of PTB among residents aged 60 years and older in Yangzhou City showed a downward trend from 2013 to 2022. Particular attention should be payed to males, residents aged 75- <80 years, and the elderly in Jiangdu District and Baoying County.

Intrahepatic cholangiocarcinoma （ICC） is a highly malignant liver tumor， and due to the absence of symptoms in its early stage and the lack of effective treatment measures， patients tend to have an extremely low 5-year survival rate. The tumor stroma-immune microenvironment （TSIME） is a complex ecosystem that changes dynamically during tumorigenesis and evolution and consists of a variety of cellular and non-cellular components， and it plays an important role in the development， proliferation， invasion， and progression of ICC and determines the heterogeneity and malignancy of ICC to a certain degree. This article reviews the cellular components （such as T cells， B cells， natural killer cells， dendritic cells， neutrophils， macrophages， myeloid-derived suppressor cells） and non-cellular components （such as chemokines and cytokines） within the ICC TSIME， as well as the complex mechanisms of interaction between these components， and it also reviews the spatial interactions between immune cells and tumor cells， in order to provide potential research directions for ICC immunotherapy and new ideas for the effective and precise treatment of ICC in the future.