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.

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 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.

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.

Objective : To investigate the role and related mechanisms of IgD on the viability , proliferation , apoptosis , and other functions of Molm_13 cells. Methods: Peripheral blood serum was collected from AML patients and healthy controls. The sIgD levels were quantified by ELISA. For in vitro studies , Molm_13 cells were treated with varying concentrations of IgD. Cell viability and proliferation were assessed via CCK_8 assays , CFSE staining , and colony formation assays. Apoptosis rates were determined using an Annexin V/PI apoptosis detection kit. Preliminary exploration of the mechanisms related to IgD_induced proliferation of Molm_13 were analyzed through differential gene analysis. Results: Compared with healthy controls , the levels of sIgD in AML patients were significantly el_ evated (P < 0. 001 ) . IgD treatment dose_dependently increased Molm_13 cell viability and proliferation ( P < 0. 05) , inhibited apoptosis rates (P < 0. 001) . Conclusion IgD promotes the viability and proliferation of Molm_ 13 cells , and reduces apoptosis.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

Cultivating innovative medical talents is a key strategy for enhancing a hospital's core competitiveness.Taking Zhejiang Cancer Hospital as a case study,this paper constructs a lifelong training system for innovative medical talents based on the"Triple-Phase Cultivation Framework(three stages,four integrations,five mechanisms)".This system delineates the cultivation cycle in-to three stages aligned with talent development trajectories:the"30s Start-up Phase"(young talents under 35),the"40s Growth Phase"(core professionals under 45),and the"50s Breakthrough Phase"(academic leaders under 50).It implements a four-dimensional cultivation model integrating medicine with research,education,engineering/informatics,and industry.Furthermore,a com-prehensive guarantee mechanism is established,encompassing policies & systems,platform re-sources,project drivers,financial investment,and talent teams.Practice demonstrates that this system has significantly enhanced talent development effectiveness.Over the past five years,the hospital has established 2 academician workstations and recruited 10 academician teams.The annual number of postdoctoral researchers has surged from 4 in 2020 to 58 in 2024.A total of 71 innova-tive talents have been selected across three batches,with 69 recognitions in provincial/ministerial-level talent programs,placing the hospital among the leaders within hospitals directly under the Zhejiang Provincial Health Commission.Notably,the hospital achieved a"zero breakthrough"in in-dependently cultivating national-level talents,including recipients of the National Ten-Thousand Talent Program(Young Top Talents)and the Postdoctoral Innovative Talent Support Program.The"Triple-Phase Cultivation Framework"establishes a replicable paradigm for nurturing innovative medical talents through its full-career-cycle approach,multidisciplinary integration,and systematic support mechanisms,offering valuable insights for talent strategies in specialized cancer hospitals.

Under the context of the research-oriented hospital construction strategy and national medical talent cultivation policies,postdoctoral research stations have emerged as vital platforms for assembling high-level innovative talents.Based on the construction practices of the postdoctoral research station at Zhejiang Cancer Hospital,this paper focuses on its development trajectory from humble beginnings to being recognized as the only"Excellent medical institution-affiliated post-doctoral work station"in Zhejiang Province.It analyzes the achievements in constructing high-standard organizational management systems,high-caliber mentor teams,and high-investment talent support systems.Addressing existing challenges,the study proposes development strategies in-cluding broadening recruitment channels,exploring diversified training models,striving for inde-pendent recruitment authority,and promoting synergistic development with research-oriented hos-pital initiatives.The aim is to provide replicable experience and insights for postdoctoral platforms in tumor specialty hospitals to empower the construction of research-oriented hospitals.

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.