ObjectiveTo investigate the effect of quercetin on acute gouty arthritis （GA） in rats by inhibiting the reactive oxygen species （ROS）/NOD-like receptor protein 3 （NLRP3）/interleukin-1β （IL-1β） signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal， model， colchicine （0.3 mg·kg^-1）， and low-， medium-， and high-dose （25， 50， 100 mg·kg^-1， respectively） quercetin groups （n=10）. The rats in the dosing groups were administrated with the corresponding drugs （10 mL·kg^-1） by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5， an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate （MSU） suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6， 12， 24， 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin （HE） staining. Malondialdehyde （MDA）， xanthine oxidase （XOD）， and total superoxide dismutase （T-SOD） assay kits were used to assess the levels of MDA， XOD， and T-SOD in the serum. The levels of tumor interleukin-6 （IL-6）， necrosis factor-α （TNF-α）， and IL-1β in the rat serum， as well as ROS in the ankle joint tissue， were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was performed to determine the protein levels of NLRP3， thioredoxin-interacting protein （TXNIP）， apoptosis-associated speck-like protein containing a CARD domain （ASC）， precursor cysteinyl aspartate-specific proteinase-1 （pro-Caspase-1）， cleaved Caspase-1 （Caspase-1 p20）， and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue. ResultsCompared with the normal group， the model group exhibited decreased spontaneous activity， mental fatigue， increased ankle joint swelling and gait scores （P<0.01）， aggravated synovial tissue edema and inflammatory cell infiltration （P<0.01）， elevated levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， a declined level of T-SOD （P<0.01）， up-regulated protein levels of NLRP3， TXNIP， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.01）， and up-regulated mRNA levels of NLRP3， TXNIP， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Compared with the model group， the medium- and high-dose quercetin groups showed improved general conditions， decreased gait scores （P<0.05， P<0.01）， reduced joint swelling （P<0.01）， alleviated synovial tissue edema and inflammatory cell infiltration （P<0.05， P<0.01）， lowered levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， increased levels of T-SOD （P<0.01）， down-regulated protein levels of TXNIP， NLRP3， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.05， P<0.01）， and down-regulated mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Low-dose quercetin also ameliorated some of the above parameters （P<0.05， P<0.01）. ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway， downregulating NLRP3 inflammasome activation， and inhibiting the production of pro-inflammatory cytokines including TNF-α， IL-1β， and IL-6.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective:To evaluate the effect of disulfiram on sepsis-associated encephalopathy (SAE) and the relationship with NOD-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 signaling pathway in rats.Methods:Forty-five SPF healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-220 g, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group, SAE group, and SAE+ disulfiram group (SAE+ DSF group). The SAE model was established by by using cecal ligation and puncture in anesthetized rats. SAE+ DSF group received an intraperitoneal injection of 50 mg/kg disulfiram 4 h before the cecal ligation and puncture. The survival status of rats was recorded within 72 h after surgery. Their neurobehavioral scores were assessed and recorded on days 1-3 after surgery. On the 3rd day after surgery, novel object recognition test (cognitive index) and open field test (activity distance and time in the central area) were conducted sequentially. Following the behavioral testing, the rats were anesthetized, and their hippocampi were dissected and isolated to observe the pathological changes in the hippocampal region (using HE staining) and to determine the expression of NLRP3 and caspase-1 (by Western blot) and the expression of interleukin-1beta (IL-1β), IL-18 and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction). Results:Compared with Sham group, the 72-h survival rate and postoperative neurobehavioral scores were significantly decreased, the activity distance and time in the central area of the open field were shortened, and the cognitive index was decreased, the expression of NLRP3, caspase-1 and IL-1β, IL-18 and TNF-α mRNA was up-regulated ( P<0.05), and the pathological damage was marked in the hippocampus in SAE group ( P<0.05). Compared with SAE group, postoperative neurobehavioral scores were significantly increased, the activity distance and time in the central area of the open field were prolonged, the cognitive index was increased, and the expression of NLRP3 and caspase-1 and IL-1β, IL-18 and TNF-α mRNA was down-regulated ( P<0.05), no significant change was found in the 72-h survival rate ( P>0.05), and the pathological damage to the hippocampus was significantly alleviated in SAE+ DSF group. Conclusions:Disulfiram can alleviate SAE in rats, and the mechanism may be related to the inhibition of the NLRP3/caspase-1 signaling pathway.

BACKGROUND: Previous studies have demonstrated that short-term exposure to ambient particulate matter elevates the risk of ischemic stroke in major urban areas of various countries. However, there is a notable gap in research focusing on remote areas inhabited by ethnic minorities and the cumulative effects of air pollutants. Our study conducted in the area aims to explore the potential association between ischemic stroke and air pollutants and contribute to improving health outcomes among the community. METHODS: This retrospective observational study was conducted at the Xing'an League People's Hospital in Inner Mongolia. The medical records of 4,288 patients admitted for IS between November 1, 2019, and October 31, 2020, were reviewed. Data on demographics (age and sex), air pollutants (PM₁₀, PM_2.5, NO₂, NO, CO, and O₃), and meteorological factors (daily average temperature, daily average wind speed, and daily average atmosphere pressure) were collected and analyzed. The statistical analysis included descriptive statistics, Poisson distribution analysis to evaluate the adverse effects of atmospheric pollutants on daily hospitalizations, and subgroup analysis to determine whether gender and age could modify the impact on hospitalizations. RESULTS: A substantial correlation was revealed in single-day lags model. The peak delayed effects of PM₁₀, PM_2.5, SO₂, and NO₂ were observed at lag8 (PM₁₀ (OR = 1.016, 95%CI 1.002, 1.030), PM_2.5 (OR = 1.027, 95%CI 1.007, 1.048), SO₂ (OR = 1.153, 95%CI 1.040, 279) and NO₂ (OR = 1.054, 95%CI 1.005, 1.105)) while males exhibited a consistent trend from lag0 to lag8 (PM₁₀ (OR = 1.035, 95%CI 1.018, 1.053), PM_2.5 (OR = 1.056, 95%CI 1.030, 1.082), SO₂ (OR = 1.220, 95%CI 1.072, 1.389), NO₂ (OR = 1.126, 95%CI 1.061, 1.120), CO (OR = 10.059, 95%CI 1.697, 59.638) and O₃ (OR = 0.972, 95%CI 0.946, 0.999)). When gender and age were considered, a positive impact was also observed after three days cumulative effect in males. CONCLUSIONS There is a significant cumulative effect of exposure to air pollution on IS hospital admissions, especially the males and patients under the age of 65. Our results also suggested that a notable association between CO and NO₂ in two-pollutant models.
Humans ; Male ; Female ; Air Pollution/analysis* ; China/epidemiology* ; Retrospective Studies ; Middle Aged ; Air Pollutants/analysis* ; Aged ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Adult ; Ischemic Stroke/chemically induced* ; Environmental Exposure/adverse effects* ; Aged, 80 and over

Peptide-based drugs possess several advantages, including high specificity, low immunogenicity, minimal accumulation, and fewer drug-drug interactions, making them a novel and efficient therapeutic class for various diseases. In recent years, peptide-based drugs have shown great potential and broad application prospects in the treatment of oral infectious diseases, tissue injury and repair, tumors, and complex oral mucosal disorders, acting either through direct mechanisms or indirect modulation. Oral administration remains the preferred route due to its non-invasive, painless nature and ease of management; however, gastrointestinal pH can inactivate or even degrade peptide drugs. In the treatment of oral diseases, local administration is commonly employed, avoiding gastrointestinal degradation and first-pass metabolism. Nevertheless, limitations in current theoretical research and the high cost of peptide synthesis hinder their clinical application. Future efforts should focus on advancing related studies to promote the practical application of peptide-based drugs in the field of oral medicine.
Humans ; Peptides/administration & dosage* ; Mouth Diseases/drug therapy* ; Administration, Oral

OBJECTIVE: To observe the clinical efficacy of acupuncture based on "status-target coherence" theory combined with Kegel exercises for vaginal laxity syndrome (VLS). METHODS: Sixty-six patients with VLS were randomized into an observation group (33 cases, 2 cases dropped out, 1 case was discontinued) and a control group (33 cases, 5 cases dropped out). The observation group was treated with acupuncture combined with Kegel exercises, acupuncture was applied to bilateral Ciliao (BL32), Zhongliao (BL33), Sanyinjiao (SP6), etc. The control group was treated with Kegel exercises. Both acupuncture and Kegel exercises were performed once every other day, three times a week for 12 weeks. Before and after treatment, the vaginal laxity questionnaire (VLQ) score, pelvic floor muscle strength (vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration), degree of vaginal laxity and sexual satisfaction questionnaire (SSQ) grade were observed in both groups. RESULTS: After treatment, the VLQ score, vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration in the observation group were elevated compared with those before treatment (P<0.05), and SSQ grade was improved (P<0.05); and the above indexes in the observation group were better than those in the control group (P<0.05). There were no significant difference before and after treatment in the degree of vaginal laxity in the two groups (P>0.05). CONCLUSION Acupuncture based on "status-target coherence" theory combined with Kegel exercises can effectively enhance the strength of pelvic floor muscles, improve the symptoms of vaginal laxity, and improve the satisfaction of sexual life, and its therapeutic effect is better than Kegel exercises alone.
Humans ; Female ; Adult ; Vagina/physiopathology* ; Acupuncture Therapy ; Exercise Therapy ; Young Adult ; Middle Aged ; Treatment Outcome ; Acupuncture Points ; Combined Modality Therapy ; Vaginal Diseases/therapy*

Objective:To investigate the correlation between triglyceride-glucose-body mass index (TyG-BMI index) and the outcome of young patients with acute ischemic stroke (AIS).Methods:Consecutive young patients with first-ever AIS (aged 18-45 years) admitted to Pingyi County People's Hospital and Qingdao Municipal Hospital from January 2020 to December 2023 were included retrospectively. The demographic data, vascular risk factors, baseline blood pressure, baseline laboratory tests, classification of stroke etiology, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and main treatment methods were collected. At 3 months after the onset of stroke, the modified Rankin Scale was used for outcome evaluation. A score of 0-2 was defined as good outcome and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent factors associated with poor outcome in young patients with AIS. Results:A total of 253 young patients with AIS were enrolled, including 196 males (77.5%), aged 38.65±5.34 years; baseline NIHSS score 3.03±2.88. At 90 days after onset, 206 patients (81.4%) had good outcome, while 47 (18.6%) had poor outcome. The poor outcome group had significantly higher systolic blood pressure, triglycerides, fasting blood glucose, triglyceride glucose (TyG) index, body mass index (BMI), TyG-BMI index, and baseline NIHSS score than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, systolic blood pressure, baseline NIHSS score, and antiplatelet drug use, the TyG-BMI index was significantly independently associated with the poor outcome in young patients with AIS (odds ratio 1.039, 95% confidence interval 1.021-1.057; P<0.001). Conclusion:A higher baseline TyG-BMI index is independently associated with the poor outcome in young patients with AIS.

Knee osteoarthritis(KOA)is a common musculoskeletal disease,and ferroptosis is a new type of programmed cell death involving iron ions.This paper summarized the relationship between the pathological changes of ferroptosis and the onset of KOA,and reviewed the progress of traditional Chinese medicine(TCM)intervention in KOA based on the pathological changes of ferroptosis.The pathological changes of ferroptosis are mainly related to the imbalance of amino acid antioxidant system,iron metabolism disorder and lipid peroxide accumulation.The cystine/glutamate antiporter(System XC-),glutathione(GSH)and glutathione peroxidase 4(GPX4)are the core targets for regulating ferroptosis,involving the main signaling pathways for studying the TCM intervention of KOA via ferroptosis.Single herbs such as Drynariae Rhizoma,Scutellariae Barbatae Herba,Epimedii Folium,Astragali Radix,Ligustri Lucidi Fructus,and Achyranthis Bidentatae Radix,and multi-herb formulae such as Duhuo Jisheng Decoction and Yougui Pills,can inhibit the ferroptosis of chondrocytes through multiple targets and multiple pathways,thus treating KOA.The research of the TCM intervention on the ferroptosis of chondrocytes and its associated signaling pathways can provides a novel approach for expanding the TCM therapy of KOA.

Objective: To analyze the current status and influencing factors of psychological crisis among college students, so as to provide a scientific basis for the formulation of psychological crisis intervention plans in colleges and universities. Methods: From September to December 2024, 645 college students from a medical undergraduate university in Heilongjiang Province were selected with a convenience sampling method. A convergent mixed analysis design was used. Quantitative analysis was conducted using College Students Psychological Crisis Screening Scale, Emotion Regulation Questionnaire, Short-Egna Minnen av Barndoms Uppfostran and Perceived School Climate Scale. Binary Logistic regression analysis was used to explore the related factors of psychological crisis among college students. Qualitative research was conducted on 15 college students with psychological crisis identified in the quantitative analysis by a purposive sampling method. The interview data were organized and analyzed using the thematic framework analysis method. Results: Among the surveyed college students, 92 (14.3%) had psychological crisis. Binary Logistic regression analysis results showed that positive parenting style ( OR=0.97,95%CI =0.95-0.99), negative parenting style ( OR=1.01,95%CI =1.00-1.02), cognitive reappraisal ( OR=0.88, 95%CI =0.83-0.92), expressive suppression ( OR=1.08, 95%CI =1.02-1.15), and perceived campus atmosphere ( OR=0.97, 95%CI =0.95-0.98) were all related factors of psychological crisis among college students ( P <0.05). The qualitative analysis results showed that there were three themes for the influencing factors of college students psychological crisis, including differential impact of emotion regulation strategies on psychological state, shaping of psychological state of college students by family and bidirectional effect of perceived campus atmosphere on psychological state. Mixed analysis results showed that the influencing factors of college students psychological crisis were consistent in terms of emotion regulation strategies, and were expansive in terms of parenting style and perceived campus atmosphere. Conclusion Schools and mental health service departments can reduce the risk of psychological crisis by optimizing cognitive reappraisal and reducing expressive suppression, improve the level of psychological crisis by strengthening positive family interaction and blocking negative parenting style, and maintain the mental health level of college students by building a supportive campus environment and alleviating high pressure.

OBJECTIVE To evaluate the efficacy and safety of high-dose ilaprazole combined with amoxicillin for newly diagnosed elderly patients with Helicobacter pylori （Hp） infection， and analyze independent risk factors for failure of Hp infection eradication treatment. METHODS Totally 200 cases of newly diagnosed elderly patients with Hp infection in Xinxiang Central Hospital from August 1， 2021 to December 1， 2024 were selected and randomly divided into control group and study group， with 100 cases in each group. The control group was treated with classic quadruple therapy regimen （Amoxicillin capsules+ Clarithromycin tablets+Bismuth potassium citrate tablets+Ilaprazole enteric-coated tablets）. The study group was treated with high- dose Ilaprazole enteric-coated tablets+Amoxicillin capsules. All patients were administered medication for 2 weeks. Hp eradication rates in the two groups were compared using intention-to-treat （ITT） and per-protocol （PP） analyses. The incidence of adverse reactions in both groups was also recorded. The multiple-factor Logistic regression analysis was used to identify independent risk factors for failure of Hp infection eradication treatment. RESULTS In ITT and PP analyses， there was no significant difference of Hp eradication rates between the two groups （P＞0.05）. There was no significant difference in incidence of mild to moderate adverse reactions between the two groups （P＞0.05）. BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease were identified as independent risk factors influencing the failure of Hp infection eradication treatment （P＜0.05）. CONCLUSIONS The efficacy and safety of high-dose ilaprazole combined with amoxicillin are comparable to classic quadruple therapy regimen in treating newly diagnosed elderly patients with Hp infection. Independent risk factors influencing the failure of Hp infection eradication treatment include BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease.