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 analyze the diversity of Duffy blood group gene among ethnic Hui population from Henan Province using PacBio long-read sequencing technique.Methods:Randomly select 30 individuals with three generations of Hui ancestry from Henan as the study subjects. Full-length sequences of the Duffy blood group gene were obtained through PacBio long-read sequencing. Distribution of the predicted phenotype and genotype frequency were determined, and the linkage between Duffy haplotypes and variation sites was analyzed. Genetic diversity, natural selection pressure, and population genetic characteristics were evaluated. This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Zhengzhou University (Ethics No. 202223).Results:The predicted Duffy blood group phenotype in the Henan Hui population was predominantly Fy(a+ b-). Three novel SNPs in the FY*01 allele were identified, with a total frequency of 13.33%, among which FY*01.NEW1 (c.199C>T) was the most common. A total of 32 variant sites were identified, with 28 located in intronic regions, indicating that genetic diversity was primarily concentrated in introns. The Duffy blood group gene was under negative selection pressure ( dN/ dS < 1, Tajima′s D, Fu and Li′s D*& F* significantly deviated from 0), suggesting overall conservation. The allele frequencies of Duffy blood group in the Henan Hui population was similar to that of the Xinjiang Hui, Xinjiang Kazakh, Inner Mongolia Mongolian, and Yuncheng Han populations, but significantly different from those of most Han and other ethnic groups ( P<0.05). Conclusion:This study revealed the characteristics of the Duffy blood group gene among the Henan Hui population and demonstrated the significant advantages of PacBio long-read sequencing technique in haplotype analysis, genetic diversity study, and novel mutation identification.

Objective:To explore the correlation between quantitative parameters based on SUV acquired by dynamic SPECT/CT imaging of parotid glands and pathological grading of labial gland in patients with primary Sj?gren syndrome (pSS).Methods:Seventy-two patients (6 males, 66 females, age (51.5±13.8) years) with confirmed pSS diagnosed at Hebei General Hospital between August 2022 and March 2024 were prospectively included. The clinical data and pathological grading information from labial gland biopsies were analyzed. Dynamic SPECT/CT imaging of the parotid glands was performed, and quantitative parameters based on SUV were obtained using Q-metrix software: SUV max, SUV mean, uptake volume of parotid glands (UVP) and total parotid uptake (TPU) pre/post-acid stimulation, as well as the differences in quantitative parameters before and after acid stimulation (ΔSUV max, ΔSUV mean, ΔUVP, and ΔTPU). The independent-sample t test or Mann-Whitney U test was performed to evaluate the differences in parameters between patients with pathological grade 1-2 and those with pathological grade 3-4. Spearman rank correlation was used to analyze the correlation between quantitative parameters and pathological grading. The performance of quantitative parameters in distinguishing pathological grade 1-2 from grade 3-4 was assessed using ROC curve analysis with Delong test. Results:The SUV max pre/post-acid stimulation in patients with pathological grade 1-2 ( n=30) were higher than those in patients with grade 3-4 ( n=42) (36.38(27.81, 44.17) vs 15.45(10.77, 24.51), Z=-5.51, P<0.001(pre-acid stimulation); 21.53(16.93, 26.21) vs 11.33(7.32, 15.89), Z=-5.27, P<0.001 (post-acid stimulation)). SUV mean, UVP and TPU pre/post-acid stimulation in patients with pathological grade 1-2, as well as ΔSUV max, ΔSUV mean and ΔTPU, were all significantly higher ( Z values: from -4.73 to -3.04, t values: 6.39, 4.50, all P<0.01). Moreover, these parameters were negatively correlated with the pathological grading ( rs values: from -0.66 to -0.36, all P<0.05). No significant difference in ΔUVP was observed between patients with pathological grade 1-2 and those with grade 3-4 ( Z=-1.05, P=0.293), and ΔUVP showed no correlation with pathological grading ( rs=-0.13, P=0.297). Among all parameters, SUV max pre/post-acid stimulation and TPU pre-acid stimulation exhibited better diagnostic performance in differentiating pathological grade 1-2 from grade 3-4, with AUC values of 0.883, 0.866, and 0.888, respectively. Delong test showed that those 3 AUC values were all higher than AUC values of SUV mean, UVP post-acid stimulation and ΔUVP (all AUC<0.800; Z values: 2.09-4.65, all P<0.05). Conclusion:The quantitative parameters of parotid glands based on SUV acquired by dynamic SPECT/CT can reflect the damage degree of parotid glands in patients with pSS, providing novel quantitative analytical tools for the functional diagnosis and assessment of pSS.

Objective:To analyze the prevalence and influencing factors of arteriosclerosis in different examination items in health check-up population.Methods:It was a cross-sectional study. A total of 4 479 subjects who underwent fundus, carotid artery color ultrasound and arteriosclerosis detector examinations in the Health Management Center at Tianjin Medical University General Hospital from January to December 2019 were selected as the study objects. The data including age, gender, family history and biochemical indicators were collected. The detection outcomes of arteriosclerosis and the distribution in different age and gender subgroups were analyzed. Kappa consistency test was used to analyze the consistency of different examination items of arteriosclerosis examination. The multiple logistic regression model was used to analyze the influencing factors of different examination items of arteriosclerosis detection. Results:Among the 4 479 subjects included in the analysis, 2 450 were male and 2 029 were female, with a mean age of (44.48±8.12) years. Arteriosclerosis was detected in one examination item in 1 167 cases (26.05%), 1 042 cases (23.26%) in two examination items, and 617 cases (13.78%) in three examination items, respectively. Among patients aged ≤40 years, 149 cases (18.91%) were detected with arteriosclerosis. In the age group of 40<-60 years, arteriosclerosis was detected in 2 660 patients (72.40%). All patients >60 years old exhibited arteriosclerosis, with 16 cases (94.12%) showing ≥2 items of arteriosclerosis. The results of fundus and carotid artery color Doppler ultrasound, fundus and arteriosclerosis detector, carotid artery color Doppler ultrasound and arteriosclerosis detector all demonstrated moderate consistency ( Kappa=0.32, 0.34, 0.24; all P<0.01). Logistic regression analysis revealed that the age ( OR=2.07, 95% CI: 1.97-2.17), male ( OR=1.60, 95% CI: 1.14-2.23), body mass index ( OR=1.10, 95% CI: 1.05-1.15), and systolic blood pressure ( OR=1.02, 95% CI: 1.01-1.03) were positively correlated with fundus arteriosclerosis (all P<0.05). Similarly, age ( OR=1.13, 95% CI: 1.12-1.14), male ( OR=2.53, 95% CI: 2.07-3.09), systolic blood pressure ( OR=1.02, 95% CI: 1.01-1.03), and low-density lipoprotein cholesterol ( OR=1.61, 95% CI: 1.16-2.23) were positively correlated with cervical arteriosclerosis, while high-density lipoprotein cholesterol ( OR=0.48, 95% CI: 0.32-0.72) was negatively correlated with cervical arteriosclerosis (all P<0.05). Furthermore, age ( OR=1.09, 95% CI: 1.08-1.11), male ( OR=1.55, 95% CI: 1.25-1.92), systolic blood pressure ( OR=1.08, 95% CI: 1.07-1.09), diastolic blood pressure ( OR=1.02, 95% CI: 1.00-1.03), postprandial blood glucose ( OR=1.09, 95% CI: 1.03-1.15), homocysteine ( OR=1.02, 95% CI: 1.00-1.03), and fibrinogen ( OR=1.26, 95% CI: 1.04-1.52) were positively correlated with systemic arterial stiffness (all P<0.05). Conclusions:The detection rates of arteriosclerosis in different examination items among the health check-up population vary. Age, male gender and systolic blood pressure are positive correlation factors for the three detection items of arteriosclerosis. For the examinees with aggregated risk factors, the multi-site and combined screening mode has certain significance for the early diagnosis and screening of arteriosclerotic diseases.

Objective:To explore the association between cumulative blood pressure (BP) and the risk of cerebrovascular disease (CVD) in older adults.Methods:This retrospective cohort study consecutively selected 4 480 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2009 as the study subjects. The cumulative BP was calculated using the area under the curve from measurements taken at baseline (2008-2009), the first follow-up (2011), and the second follow-up (2014). The subjects were grouped with the quartiles (Q1-Q4) of cumulative systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The Cox proportional hazards regression models were used to analyze the hazard ratios (HR) and 95% CI for the association between cumulative BP and the risk of CVD among older adults. The restricted cubic spline function was employed to examine the potential dose-response pattern between cumulative BP and the risk of CVD. Results:During a total of 40 230 person-years of follow-up, with a mean follow-up duration of (8.98±2.16) years, 768 new cases of CVD were identified. The older adults in the highest quartile (Q4) of cumulative SBP, DBP, and PP had a significantly higher risk of CVD compared to those in the lowest quartile (Q1), with a HR of 1.68 (95% CI: 1.36-2.06), 1.67 (95% CI: 1.36-2.06), and 1.52 (95% CI: 1.24-1.84), respectively (all P<0.001). For every 10 mmHg (1 mmHg=0.133 kPa)×year increase in cumulative SBP, DBP, and PP, the risk of CVD increased by 2% ( HR=1.02, 95% CI: 1.01-1.03), 3% ( HR=1.03, 95% CI: 1.01-1.05), and 2% ( HR=1.02, 95% CI: 1.01-1.03), respectively (all P<0.05). The restricted cubic spline model revealed a linear positive correlation between cumulative SBP, DBP, and PP with the risk of CVD among older adults (all P for nonlinearity>0.05). When cumulative SBP, DBP, and PP exceeded 791.9 mmHg×years, 462.9 mmHg×years, and 323.6 mmHg×years, corresponding to an average BP level of 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively, the risk of CVD began to increase. Conclusions:Elevated long-term cumulative BP may increase the risk of CVD in older adults. Caution is warranted when SBP, DBP, and PP exceed 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively.

Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.

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.

Objective To analyze the service efficiency and changes of county-level public hospitals in Shandong Province from 2017 to 2023,and to provide references for improving the service efficiency of county-level public hospitals.Methods Based on the deta envelopment analysis method,BCC model was used to evaluate the static service efficiency of county-level public hospitals in 16 cities in Shandong Province in 2023,and to dynamically track the change trend of efficiency from 2017 to 2023 based on Malmquist index model.Results In 2023,the average comprehensive efficiency of county-level public hospitals in Shandong Province is 0.971,and the efficiency value of county-level public hospitals in 8 of the 16 cities is 1,which is in DEA effective state;From 2017 to 2023,the average total factor productivity of county-level public hospitals in Shandong Province was 0.906,with an overall decline of 9.4%in service efficiency.Conclusion The overall service efficiency of county-level public hospitals in Shandong Province is high,but regional differences are obvious,and the technical progress index is the key to further indicate the service efficiency.Local governments need to reasonably control the scale of county-level public hospitals,continuously improve their technical level,and strengthen their internal management,so as to improve their service efficiency.

Objective To establish an analytical method for the simultaneous determination of 18 perfluoroalkyl compounds(PFCs)in tea leaves using a quick,easy,cheap,effective,rugged,and safe(QuEChERS)method for sample pretreatment combined with ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods The target analytes—18 PFCs—included 13 carboxylic acid PFCs(perfluorobutanoic acid[PFBA],perfluoropentanoic acid[PFPeA],perfluorohexanoic acid[PFHxA],perfluoroheptanoic acid[PFHpA],perfluorooctanoic acid[PFOA],perfluorononanoic acid[PFNA],perfluorodecanoic acid[PFDA],perfluoroundecanoic acid[PFUdA],perfluorododecanoic acid[PFTrDA],perfluorotridecanoic acid[PFTeDA],perfluorotetradecanoic acid[PFHxDA],perfluorohexadecanoic acid[PFHpS],and perfluorooctadecanoic acid[PFODA])and 5 sulfonic acid PFCs(perfluorobutanesulfonic acid[PFBS],perfluorohexanesulfonic acid[PFHxS],perfluoroheptanesulfonic acid[PFHpS],perfluorooctanesulfonic acid[PFOS],and perfluorodecanesulfonic acid[PFDS]).The QuEChERS pretreatment parameters were systematically optimized using the response surface methodology.The tea leave samples were extracted with an 80%acetonitrile solution and subsequently purified by adding a mixed absorbent consisting of 20 mg N-propyl-ethylenediamine(PSA),210 mg graphitized carbon black GCB),and 60 mg octadecylsilane(C18).The supernatant was concentrated by nitrogen blowing and subsequently re-dissolved in 50%methanol-2 mmol/L ammonium acetate solution.The re-dissolved solution was injected into the UHPLC-MS/MS for analysis.The target analytes were separated on an ACQUITY UPLC BEH C18 column(2.1 mm×50 mm,1.7 μm).The mobile phases consisted of methanol(phase A)and 2 mmol/L aqueous ammonium acetate(phase B),with a gradient elution procedure.The total running time was 18 min.The mass spectrometry analysis was conducted using an electrospray ionization source in negative ionization mode and multi-reaction monitoring(MRM),with quantification performed using the internal standard curve method.The greenness of the analytical method was assessed using Analytical GREEnness calculator(AGREE)and the Analytical Eco-Scale method(AES).Results Under the optimized conditions,the limits of detection(LODs)and limits of quantification(LOQs)of the method were 0.005 7-1.23 ng/g and 0.019-4.09 ng/g,respectively.The average recoveries of most target compounds were 71.1%-117.9%,with relative standard deviations(RSDs)below 15%.The AGREE index of the method was 0.49,and the AES score was 76.At least one PFC was detected in each of the 132 tea leave samples,and the detection rate of carboxylic acid PFC was higher than that of sulfonic acid PFC.The highest detection rates were observed for PFBA at 97.74%,PFHpA at 93.23%,and PFOA at 92.24%.In contrast,PFHpS,PFUdA,PFDoA,PFHxDA,and PFODA were not detected in the samples.Conclusion The proposed method has the advantages of simplicity,rapidity and sensitivity,and is suitable for the analysis of PFCs in tea leaves.The method has high greenness with minimal impact on the operator and the environment.The widespread presence of PFC contamination in tea leaves available in the market warrants strengthened monitoring and regulatory control.