The HACEK group microorganisms(Haemophilus parainfluenzae,Aggregatibacter actinomycetem-comitans,Cardiobacterium spp.,Eikenella corrodens,Kingella kingae)belong to Gram-negative bacilli and are members of the normal oropharyngeal microbiota,which can cause invasive opportunistic infection when the host immune barrier is damaged,with infective endocarditis being one of the most serious diseases.HACEK endocarditis is characterized by an insidious course,prolonged delay of diagnosis,and dependence on third-generation cephalo-sporins for treatment.In recent years,with the emergence and development of 16S ribosomal RNA gene sequencing technique,the rapid diagnosis of this disease is expected to be achieved.This paper summarizes the main clinical characteristics and research progress of infective endocarditis caused by HACEK group bacteria,aiming to provide reference for clinical diagnosis and treatment.

Objective To observe changes in voltage-dependent anion channel 3(VDAC3)in a mouse model of sepsis-induced myocardial injury and to explore its potential mechanism.Methods Twenty male C57BL/6J mice were divided randomly into a Sham group and Sepsis group,respectively(n=10 mice per group).Sepsis was induced by the cecal ligation and puncture(CLP).Serum levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,creatine kinase MB(CK-MB),and cardiac troponin T(cTnT)were detected by enzyme-linked immunosorbent assay.Pathological changes in heart tissue were observed by hematoxylin and eosin staining.Structural and functional changes in the heart were evaluated by echocardiography.Changes in total glutathione,reduced glutathione(GSH),oxidized glutathione,and malondialdehyde(MDA)in heart tissue were detected by spectrophotometry.The morphological structure of mitochondria in mouse cardiomyocytes was observed by transmission electron microscopy.Expression levels of IL-6,IL-1β,VDAC3,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),lipocalin-2(LCN2),and prostaglandin-endoperoxide synthase 2(PTGS2)mRNA were detected by real-time quantitative polymerase chain reaction and the localization and expression of VDAC3 and GPX4 proteins in mouse heart tissue were detected by immunofluorescence staining.The correlations between VDAC3 mRNA and GPX4,SLC7A11,PTGS2,LCN2,IL-6,and IL-1β mRNA were analyzed.Expression levels of VDAC3,GPX4,and SLC7A11 proteins were detected by Western blot.Results IL-6,TNF-α,CK-MB,and cTnT levels were significantly higher in the Sepsis group compared with the Sham group(P＜0.05).In the Sepsis group,myocardial fibers were torn,the ventricular wall was thickened and edematous,the mitochondrial membrane was ruptured,and mitochondrial cristae were broken or absent.GSH levels were significantly reduced in the Sepsis group(P＜0.05)and the lipid peroxide MDA was increased in the Sepsis group(P＜0.05)compared with the Sham group.VDAC3,GPX4 and SLC7A11 mRNA and protein levels were all lower in the Sepsis group compared with the Sham group(P＜0.05),while expression levels of IL-6,IL-1β,LCN2,and PTGS2 mRNA were increased(P＜0.05).VDAC3 mRNA was positively correlated with GPX4 and SLC7A11 mRNA levels,and negatively correlated with LCN2,PTGS2,IL-6,and IL-1β.Conclusions VDAC3 expression decreases in myocardial injury,and it may participate in the occurrence of sepsis-induced myocardial injury by regulating ferroptosis.

AIM:To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction(TMGTD).METHODS:SD rats were divided into sham,model,TMGTD high/medium/low-dose(20.52/10.26/5.13 g·kg-1·d-1),and Nimodipine(30 mg·kg-1·d-1)groups.A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was es-tablished using Fuzi Decoction(2 g·kg-1·d-1)and thread-occlusion.After 21 days of Fuzi decoction pretreatment,rats received daily drug administra-tion for 12 days.Syndrome indicators(irritability,24-hour water intake,24-hour urine volume,facial temperature)were recorded,plasma NE,E,cAMP,and cGMP were measured by ELISA,neurological function was assessed using Zea Longa and mNSS methods,brain histopathology was evaluated by HE staining,protein expression of soluble/insoluble p62 and LC3B was detected by Western blot,au-tophagy-related genes were analyzed by PCR array,additionally,mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot.RESULTS:Compared to the sham group,the model group showed increased irritability,24-hours water intake,24-hours urine volume,facial temper-ature,and level of NE,E,cGMP(P＜0.01),neurologi-cal scores(P＜0.01),LC3B-Ⅱ,insoluble p62,CXCR4,CXCL12 expression(P＜0.01),but decreased soluble p62(P＜0.01).TMGTD groups exhibited reduced irri-tability,water intake,urine volume,facial tempera-ture,NE,E,cGMP(P＜0.05,P＜0.01),neurological scores(P＜0.05,P＜0.01),p62 expression(P＜0.01),alongside increased LC3B-Ⅱ(P＜0.01)and improved cortical pathology.TMGD also reversed dysregulat-ed autophagy-apoptosis genes(CXCR4,Lamp1,Tgfb1,APP,Rab24)and reduced CXCR4,CXCL12 ex-pression(P＜0.01).CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model,autophagy genes were activated but flux was impaired,and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.

Warthin-like papillary renal cell carcinoma (WPRCC), which is rare in clinical practice, is a new subtype of papillary renal cell carcinoma in the 5th editon WHO Classification of Tumors of the Urinary and Male Reproductive System. In this paper, we report one case of WPRCC. The patient was admitted to the hospital due to a mass in the right kidney which was detected by magnetic resonance enhancement scan in physical examination. Subsequently, the laparoscopic partial nephrectomy was performed and the diagnosis of Warthin-like papillary renal cell carcinoma was confirmed. The patient was treated with interferon, and no recurrence and metastasis were found in the imaging examination after 7 months of follow-up.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Warthin-like papillary renal cell carcinoma (WPRCC), which is rare in clinical practice, is a new subtype of papillary renal cell carcinoma in the 5th editon WHO Classification of Tumors of the Urinary and Male Reproductive System. In this paper, we report one case of WPRCC. The patient was admitted to the hospital due to a mass in the right kidney which was detected by magnetic resonance enhancement scan in physical examination. Subsequently, the laparoscopic partial nephrectomy was performed and the diagnosis of Warthin-like papillary renal cell carcinoma was confirmed. The patient was treated with interferon, and no recurrence and metastasis were found in the imaging examination after 7 months of follow-up.

OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H2O2 in IEC-6 cells.METHODS Using IEC-6 cells as object,the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated;IEC-6 cells were divided into control group,H2O2 group,H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group.The levels of oxidant stress indexes[content of malondialdehyde (MDA),activity of superoxide dismutase (SOD),and levels of reactive oxygen species (ROS)],mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1),NADPH/quinone oxidoreductase-1 (NQO-1),cystine/glutamate anti-porter (xCT),glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected.RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells (P<0.01).Compared with the control group,MDA content,ROS level,mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly,while SOD activity,MMP,mRNA expressions of xCT,GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or P<0.05).Compared with the H2O2 group,oxidative stress indexes of H2O2+PL 25,50 μg/mL groups were reversed to different extents,MMP level was increased significantly,as well as mRNA and protein expressions of Nrf2,HO-1,NQO-1,xCT,GPX4 and FTH were up-regulated to different extents;there were statistical significances in some indexes between groups (P<0.01 or P<0.05).CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2,which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

The HACEK group microorganisms(Haemophilus parainfluenzae,Aggregatibacter actinomycetem-comitans,Cardiobacterium spp.,Eikenella corrodens,Kingella kingae)belong to Gram-negative bacilli and are members of the normal oropharyngeal microbiota,which can cause invasive opportunistic infection when the host immune barrier is damaged,with infective endocarditis being one of the most serious diseases.HACEK endocarditis is characterized by an insidious course,prolonged delay of diagnosis,and dependence on third-generation cephalo-sporins for treatment.In recent years,with the emergence and development of 16S ribosomal RNA gene sequencing technique,the rapid diagnosis of this disease is expected to be achieved.This paper summarizes the main clinical characteristics and research progress of infective endocarditis caused by HACEK group bacteria,aiming to provide reference for clinical diagnosis and treatment.