OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

OBJECTIVES: To detect prfA and hly toxin genes of Listeria monocytogenes using polymerase chain reaction (PCR) and colloidal gold technology. METHODS: L. monocytogenes DNA was extracted by boiling method. With prfA and hly of L. monocytogenes as the target genes, the 5' ends of upstream and downstream primers of prfA gene were labeled with 6-FAM and biotin, and the 5' ends of upstream and downstream primers of hly gene were labeled with digoxin and biotin, respectively, to establish the toxin gene detection method. Using cloning transformation, sequencing analysis, cloning of positive control products, the detection kid was developed and its specificity, sensitivity, reproducibility and stability were tested, followed by verification with sample testing. RESULTS: The concentration of L. monocytogenes DNA extracted by boiling method was 148.81±0.97 ng/μL, and the A₂₆₀/A₂₈₀ ratio ranged from 1.8 to 2.0. The PCR products showed a 100% homology with the gene sequences in GenBank database after cloning, transformation and sequencing. The colloidal gold strip yielded positive results only for L. monocytogenes samples without cross-reactions with Staphylococcus aureus, Escherichia coli or Bacillus cereus, and its minimum detection limit was 10^-2 ng/μL, demonstrating a 10-fold greater sensitivity of the test than agarose gel electrophoresis. The test also showed good reproducibility of the results when performed by different operators with good stability of the test strips after storage for 6 to 12 months. The test results showed that this kit could accurately and quickly detect L.monocytogenes in the test samples. CONCLUSIONS The detection kit developed in this study can simultaneously detect prfA and hly toxin genes of L. monocytogenes with good specificity, sensitivity, reproducibility and stability for use in food safety inspection.
Listeria monocytogenes/isolation & purification* ; Gold Colloid ; Bacterial Toxins/genetics* ; Polymerase Chain Reaction/methods* ; Hemolysin Proteins/genetics* ; Bacterial Proteins/genetics* ; DNA, Bacterial/genetics* ; Food Microbiology ; Heat-Shock Proteins

OBJECTIVES: To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting. RESULTS: The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC. CONCLUSIONS DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
Animals ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Diabetic Nephropathies/drug therapy* ; Receptor, Notch1/metabolism* ; Kidney/blood supply* ; Diabetes Mellitus, Experimental ; Down-Regulation ; Endothelium, Vascular/metabolism* ; Nuclear Proteins/metabolism*

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

Objective:To establish a rapid detection method for pathogenic microorganisms by combining loop-mediated isothermal amplification(LAMP)and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 12a(Cas12a)(CRISPR-Cas12a)system,and to evaluate its efficacy for detecting the thermolabile hemolysin(tlh)gene of Vibrio parahaemolyticus(Vp).Methods:Using the tlh gene of Vp as the target gene,LAMP primers and CRISPR RNA(crRNA)were designed to construct and optimize the optimal concentration ratio of each component in the LAMP-CRISPR detection system.Bacillus cereus,Staphylococcus aureus,and Escherichia coli were used as control groups,and the specificity,sensitivity,reproducibility and positive conformity rate were verified to establish a rapid LAMP-CRISPR/Cas12a method for detecting the tlh gene of Vp.Results:The method specifically detected Vp,while Bacillus cereus,Staphylococcus aureus,and Escherichia coli yielded negative results.The DNA extraction concentration of Vp was 190.67 mg·L-1 with an A(260)/(A280)ratio of 1.84.Under the reaction conditions of 37℃ with 80 cycles for 40 min using quantitative PCR(qPCR)method,when the concentrations of Cas12a protein and crRNA in the LAMP-CRISPR/Cas12a system were 50 nmol·L-1,the visual brightness and relative fluorescence intensity peaks were high.The sensitivity of LAMP CRISPR/Cas12a for detecting Vp DNA concentration could reach 10-6 mg·L-1.The reproducibility test results showed that different experimenters had consistent results in different experimental environments and times.Conclusion:The established LAMP-CRISPR/Cas12a method can rapidly detect the tlh gene of Vp with high sensitivity and specificity,and can achieve short-term visual detection in the field.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To investigate the predictive value of cardiac MR (CMR)-derived left ventricular end-systolic wall stress (LVESWS) and biventricular strain parameters for different types of heart failure in patients with myocardial infarction.Methods:This retrospective cohort study included 231 patients diagnosed with myocardial infarction by clinical and CMR criteria at the Second Affiliated Hospital of Kunming Medical University between January 2015 and July 2023. The endpoint was the occurrence of heart failure, and patients were divided into 3 groups: no heart failure ( n=85), heart failure with preserved ejection fraction (HFpEF, n=74), and heart failure with reduced ejection fraction (HFrEF, n=72). Clinical indicators such as age and infarct size were collected. CMR parameters analysis included LVESWS, left ventricular global radial strain (LVGRS), left ventricular global circumferential strain (LVGCS), left ventricular global longitudinal strain (LVGLS), right ventricular global radial strain (RVGRS), right ventricular global circumferential strain (RVGCS), right ventricular global longitudinal strain (RVGLS), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). Differences in clinical baseline data and CMR parameters among the 3 groups were tested. Univariate Cox regression analysis was performed, followed by multivariate Cox modeling of statistically significant factors. Receiver operating characteristic (ROC) analysis was conducted for the influencing factors identified in the multivariate Cox model, and Kaplan-Meier survival curves for survival time were plotted. Results:Significant differences were observed in biventricular strain parameters (LVGRS, LVGCS, LVGLS, RVGRS, RVGCS, RVGLS), LVESWS, LVEDVI, and LVESVI among the 3 groups (all P<0.05). Univariate and multivariate Cox regression analyses showed that RVGCS, age, and infarct size were independent influencing factors for HFpEF after myocardial infarction (all P<0.01), while LVESWS and LVGLS were independent influencing factors for HFrEF after myocardial infarction (all P<0.001). Further ROC analysis revealed that the areas under the curve (AUC) for RVGCS, infarct size, age, RVGCS combined with age, and RVGCS combined with age and infarct size in predicting HFpEF were 0.771, 0.607, 0.615, 0.793, and 0.805, respectively. The AUCs for LVESWS, LVGLS, and LVESWS combined with LVGLS in predicting HFrEF were 0.943, 0.925, and 0.971, respectively. Kaplan-Meier survival curves based on optimal cutoff values showed statistically significant differences in survival time between HFpEF and non-heart failure patients when grouped by RVGCS and age (all P<0.05), but no significant difference when grouped by infarct size ( P=0.400). Statistically significant differences in survival time were observed between HFrEF and non-heart failure patients when grouped by LVESWS and LVGLS (all P<0.001). Conclusion:CMR-derived LVESWS and biventricular strain parameters demonstrate significant predictive value for different types of heart failure after myocardial infarction and can serve as valuable imaging markers for heart failure management and risk stratification in patients with myocardial infarction.

Objective To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule(DZJTC)for repairing renal vascular endothelial injury in rats with diabetic nephropathy(DN).Methods Fifty male SD rat models of DN,established by left nephrectomy,high-sugar and high-fat diet and streptozotocin injection,were randomized into DN model group,low-,medium-,and high-dose DZJTC treatment groups,and DAPT(a γ-secretase inhibitor)treatment group,with 10 rats with normal feeding as the control group.DZJTC was administered by daily gavage at 0.315,0.63,or 1.26 g/kg,and DAPT(20 mg/kg,dissolved in 50%CMC-Na solution)was given by gavage every other day for 4 weeks;normal saline was given in the control and model groups.After treatment,the levels of creatinine(CRE),blood urea nitrogen(BUN),and microalbuminuria(mALB)were detected with ELISA,and renal pathologies were observed by transmission electron microscopy.Renal expressions of vascular endothelial growth factor(VEGF)and endothelin-1(ET-1)were measured by immunohistochemistry,and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting.Results The rat models of DN showed significantly increased CRE,BUN,and mALB levels,obvious renal pathologies under electron microscopy,increased renal VEGF,ET-1 and CD31 expressions,and upregulated Notch1,NICD,and MAML1 protein levels.Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE,BUN,and mALB levels,improved renal pathology,decreased VEGF,ET-1 and CD31 expressions,and lowered Notch1,NICD and MAML1 levels,and the effects were the most pronounced with high-dose DZJTC.Conclusion DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD-and MAML1-mediated Notch signaling pathway.