Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

OBJECTIVE: To investigate the biological behavior, differentiation ability, and differential gene expression of lymph node mesenchymal stem cells (MSCs) in patients with diffuse large B-cell lymphoma (DLBCL) and reactive lymphoid hyperplasia (RLH), providing a theoretical basis for clinical chemotherapy resistance. METHODS: Lymph node MSCs from patients with DLBCL and RLH were separated, passaged and cultured. The cell morphology and growth status were observed. Flow cytometry was performed to detect the immune phenotype of MSCs. The in vitro directed differentiation ability of the two types of MSCs was observed. High-throughput sequencing was used to analyze the differential gene expression and enrichment of two groups of MSCs. RESULTS: The lymph node MSCs of patients with DLBCL and RLH had similar cell morphology and growth characteristics, and both groups of MSCs expressed CD90, CD105, and CD73 on the cell surface. Compared with lymph node MSCs derived from patients with RLH, lymph node MSCs derived from DLBCL patients showed stronger osteogenic and adipogenic differentiation abilities. High-throughput sequencing results displayed that lymph node MSCs derived from DLBCL patients significantly upregulated some genes such as TOP2A, LFNG, GRIA3, SEC14L2, SPON2, AURKA, LRRC15, FOXD1, HOXC9, CDC20 and remarkably downregulated some genes such as TBC1D8, LDLR, PCDHAC2, POLH, PKP2, ANKRD37, DMKN, HSD11B1, ARHGAP20, PTGS1,etc. CONCLUSION Lymph node MSCs in DLBCL patients exhibit unique biological behavior and gene expression profiles, which may be closely related to clinical chemotherapy resistance.
Humans ; Mesenchymal Stem Cells/cytology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Differentiation ; Lymph Nodes/pathology* ; Pseudolymphoma/pathology*

OBJECTIVE: To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). METHODS: The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. RESULTS: In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). CONCLUSION Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use* ; Osteosarcoma/enzymology* ; Cisplatin/therapeutic use* ; Humans ; Cell Line, Tumor ; Animals ; Apoptosis/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MAP Kinase Signaling System/drug effects* ; Bone Neoplasms/enzymology* ; Cell Cycle/drug effects* ; Xenograft Model Antitumor Assays ; Mice ; Drug Resistance, Neoplasm/drug effects* ; Neoplasm Invasiveness ; Mice, Inbred BALB C

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To evaluate the impact of Diagnosis-Intervention Packet(DIP)payment reform on medical service costs and efficiency for inpatients in public hospitals,and to compare differences between surgical and medical groups.Methods:A quasi-experimental design was employed,using 605 636 discharged patients from a tertiary hospital in Hebei Province between January 2020 and March 2025 as the sample.The difference-in-differences(DID)model was used to analyze the changes in key indicators between the DIP settlement group(intervention group)and the non-DIP settlement group(control group).Results:Total hospitalization costs,out-of-pocket expenses,and medication costs were significantly reduced in the DIP settlement group(P<0.05),while costs for examinations,nursing,laboratory tests,and treatments increased significantly(P<0.05).Material costs increased by 30.7%in the surgical group(P<0.1)and decreased by 19.8%in the medical group(P<0.01).In terms of efficiency,the average length of stay,time,and cost consumption index all decreased(P<0.01),while the proportion of medical services increased(P<0.01).The case mix index(CMI)showed no significant changes.Conclusion:The DIP reform effectively controlled costs and improved efficiency,but it also resulted in cost shifting and departmental disparities.Therefore,it is necessary to optimize cost control and departmental management policies.

Objective:To optimize the previously established Improved Membrane Filtration(ISET)method for de-tecting circulating tumor cells(CTCs)and to develop and validate a new,reliable CTC detection method by combining it with immunofluorescence techniques.Methods:The study involved optimizing the CTC detection system using mixed samples of gastric cancer 803 cell lines and peripheral blood(PB)from healthy volunteers to simulate the peripheral blood of cancer patients.The optimized system was validated using peripheral blood samples from 23 patients with ad-vanced(Ⅲ/Ⅳ)cancer,employing the ISET technique combined with immunocytochemistry(ICC)and paraffin block im-munohistochemistry(IHC)identification techniques.A cohort of 74 patients with various cancer types was used to com-pare the diagnostic performance of the membrane filtration combined with immunofluorescence(ISET-ICC)system against the CTC-Biopsy and CellSearchTM methods.Results:By adding a red blood cell lysis step and increasing the membrane pore size to 10 μm,the filtration time of the ISET method was reduced by threefold.The ISET-ICC detection method achieved a CTC positivity rate of 65.2％.The combination of the ISET-ICC system with the cell paraffin block-IHC method enhanced the reliability of identifying circulating tumor cells undergoing epithelial-mesenchymal transition(EMT-CTCs).The ISET-ICC technique demonstrated a significantly higher CTC positivity rate(17.6％;13/74)within the study cohort compared to the CellSearchTM method,which showed a CTC positivity rate of 12.2％(9/74;x2=10.21,P=0.007).The difference in positive detection rates among patients at different stages was statistically significant(x2=3.64,P=0.029),with a notably higher CTC detection rate in stage Ⅳ patients compared to those in stages Ⅰ-Ⅲ(x2=6.76,P=0.001).Conclusion:The improved ISET-ICC system effectively detects CTCs across various cancer types and dem-onstrates greater accuracy compared to the CellSearchTM system.