Pan vascular disease （PVD） is a systemic vascular disorder that has become the leading cause of death among the Chinese residents， and there is currently a lack of effective systemic treatment options. Clinical practice has found that the traditional Chinese medicine （TCM） method of kidney tonification can effectively intervene in PVD and target key pathological mechanisms of PVD recognized in Western medicine. Accordingly， this paper conducts research from the following three aspects： First， it clarifies that immune dysregulation， metabolic disorders， and genetic susceptibility constitute the core pathological mechanisms of PVD in Western medicine. Typical pathological manifestations include progressive vascular endothelial injury， lipid deposition， and plaque formation， ultimately leading to multi-organ damage and dysfunction. PVD activates pathways such as the NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， triggering immune dysregulation； it also induces disorders of mitochondrial energy metabolism， water-salt metabolism， and hormonal metabolism， synergizing with genetic susceptibility factors （e.g.， apolipoprotein E gene） to accelerate vascular homeostasis imbalance. Second， this study analyzes the intrinsic relationship between the TCM theory of "kidney deficiency" and the "immune-metabolic-genetic" axis， revealing the theoretical basis for kidney tonification in intervening PVD. The kidney stores essence， governs bones， and produces marrow， which is related to the generation and differentiation of immune cells. It regulates Qi transformation and governs water， overseeing material and energy metabolism. The kidney is the root of congenital essence and governs reproduction， closely related to genetic mechanisms. Third， by integrating modern clinical research， this study elaborates on the unique advantages and clinical value of kidney tonification in targeting the "immune-metabolic-genetic" axis of heart， brain， and kidney organs. Traditional kidney-tonifying formulas and their active ingredients improve immune-inflammatory responses， enhance material and energy metabolism homeostasis， and modulate epigenetic pathways through multiple pathways， targeting various pathways to intervene in PVD. This study systematically elucidates the scientific connotation of kidney tonification in treating PVD， providing theoretical support and practical guidance for integrated TCM-Western medicine approaches and contributing to innovation and improvement in diagnostic and treatment strategies for PVD.

Panvascular diseases represent systemic vascular disorders characterized by atherosclerosis as their core pathological feature. Their incidence rates continue to rise， posing significant challenges for clinical management. Based on Traditional Chinese Medicine （TCM） theory of ''positive deficiency phlegm stasis''， this study delved into the pivotal role of mitochondrial homeostasis dysregulation in the pathogenesis and progression of pan-vascular diseases， along with its intrinsic connection to TCM pathogenesis. Mitochondrial homeostasis dysregulation pervades the entire course of these diseases， with mitochondrial oxidative stress serving as the initiating factor. Excessive reactive oxygen species （ROS） trigger endothelial dysfunction， lipid accumulation， and inflammatory initiation. Additionally， the imbalance between mitochondrial autophagy and apoptosis constitutes a pivotal link in disease progression. Excessive or insufficient autophagy may lead to the accumulation of damaged mitochondria and excessive cellular apoptosis， thereby promoting plaque instability. Furthermore， mitochondrial metabolic reprogramming impairs energy supply and function in vascular wall cells， hindering subsequent vascular repair. These pathological processes constitute the microscopic manifestation of the core pathogenesis， which is characterized by ''the intermingle of phlegm and stasis and the deficiency of healthy Qi''. Specifically， the endogenous phlegm-turbidity drives mitochondrial oxidative stress injuries， the mutual entanglement of phlegm and stasis induces an imbalance between mitochondrial autophagy and apoptosis， while deficiency of healthy Qi propels mitochondrial energy metabolism disorders and reprogramming. In view of this， this study proposed to employ phlegm-resolving and turbidity-clearing methods to mitigate mitochondrial oxidative stress injuries， phlegm-resolving and blood-activating methods to regulate mitochondrial autophagy and apoptosis， and spleen-tonifying and kidney-nourishing methods to modulate mitochondrial metabolic reprogramming. This approach can prevent and treat panvascular diseases by multi-target regulation of mitochondrial homeostasis， providing a theoretical framework and therapeutic strategies for the prevention and treatment of panvascular diseases through integrated Chinese and Western medicine.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

The aim of this study was to identify the Salmonella strains isolated from an outbreak of foodborne illness in a seafood buffet restaurant and analyze their pathogenic characteristics.Epidemiological data,fecal samples from patients and chefs,and food/environmental samples from the restaurant were analyzed.Research methods included bacterial culture,serotyping,quadruple fluo-rescence PCR identification,whole-genome sequencing and antibiotic susceptibility testing.The results showed that 4 S.Java strains(serotype 1,4,12∶b∶1,2;ST42)were isolated from two outbreak cases and two sporadic cases.All isolates exhibited similar genomic features,harboring 9 virulence islands and 98 virulence genes.Antimicrobial resistance profiling revealed streptomycin monoresis-tance,mediated by aac(6′)-Iy and aac(6′)-Iaa genes.In conclusion,this event was the first reported outbreak of foodborne illness caused by S.Java in China,indicating that S.Java may be prevalent in the surveyed district.The catering industry should optimize food handling and processing procedures and enhance the surveillance of high risk pathogens.Meanwhile,further studies should ad-dress differential diagnosis and pathogenic mechanism differences between S.Java and S.paratyphi B,which will facilitate evidence-based monitoring in China.

BACKGROUND: At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS: Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS: Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001). CONCLUSIONS It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.
Humans ; Male ; Prostatectomy/methods* ; Prostatic Neoplasms/diagnosis* ; Middle Aged ; Aged ; Positron Emission Tomography Computed Tomography/methods* ; Biopsy ; Multiparametric Magnetic Resonance Imaging ; Prostate-Specific Antigen/metabolism*

Objective In this study,we aimed to predict the inhibitory mechanism of Shenlingcao oral liquid(SLC)in non-small cell lung cancer(NSCLC)by network pharmacology and verify it by molecular docking and in vivo experiments.Methods The active ingredients and corresponding targets of SLC and NSCLC were obtained by database and literature search.Targets of SLC common to NSCLC were selected to construct the protein interaction network,and GO and KEGG enrichment analysis and molecular docking were performed.A Lewis lung cancer mouse model was constructed and divided into Model group,SH group,and SL group.The latter two groups were intragastrically administered 8.75 g SLC lyophilized powder/kg and 3.50 g SLC lyophilized powder/kg,respectively.After 14 days of drug intervention,tumor growth,pathological changes in tumor tissue,and apoptosis in tumor tissue were observed in tumor-bearing mice;changes in blood routine indexes and the tumor tissue expression of p-AKT,AKT,p-PI3K,PI3K,and Bcl-2 protein of mice were detected.The result of the KEGG enrichment analysis were verified.Results Network pharmacological analysis showed that there were 77 active ingredients,618 potential targets,1498 potential targets for NSCLC,and 179 drug and disease intersection targets.Target intersection enrichment analysis showed that they were mainly concentrated in the phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and other related pathways.Molecular docking showed that the top 10 core components had good bonding ability with the top 10 core targets.In the animal experiments,compared with the Model group,SH group and SL group had significantly decreased tumor volume and weight(P＜0.05,P＜0.01),and significantly decreased white blood cell,neutrophil,and monocyte numbers(P＜0.01,P＜0.001).Red blood cells,platelets,and hemoglobin were significantly increased(P＜0.05,P＜0.01,P＜0.001);apoptotic cells were significantly increased in early tumor tissue(P＜0.05,P＜0.01),and the protein expression levels of p-PI3K/PI3K,p-AKT/AKT,and Bcl-2/GAPDH were significantly decreased(P＜0.05,P＜0.01).The expression levels of PI3K,AKT1,and Bcl-2 genes were significantly decreased(P＜0.05,P＜0.01).Conclusions The mechanisms of SLC activity against NSCLC may be related to the activation of the PI3K-AKT pathway and the promotion of apoptosis.

Objective To observe the value of changes of neutrophil-to-lymphocyte ratio(NLR)before and after the first interventional treatment of hepatocellular carcinoma(HCC)for predicting patient's overall survival(OS).Methods Totally 92 HCC patients who underwent the first time TACE or TACE+hepatic artery infusion chemotherapy(HAIC)were retrospectively enrolled.The patients were divided into NLR ratio(NLRR)＜1.29 group(n=54)and≥1.29 group(n=38)based on the ratio of NLR after to before treatment,also ΔNLR＜0.87 group(n=60)and≥0.87 group(n=32)based on the difference of NLR after and before treatment.Clinical data were compared between groups,survival analysis was performed,and the value of NLRR and ΔNLR for predicting OS were analyzed.Results No significant difference of clinical data was found between NLRR＜1.29 and≥1.29 groups,nor between ΔNLR＜0.87 and≥0.87 groups(all P＞0.05).The median OS of 92 patients was 30.90 months,which in NLRR＜1.29 group(55.10 months)was longer than that in NLRR≥1.29 group(22.30 months,P=0.005),while in ΔNLR＜0.87 group(55.10 months)was longer than that in ΔNLR≥0.87 group(14.20 months,P=0.003).Cox regression analysis showed that the maximum diameter of tumor≥5 cm,distant metastasis,ascites,NLRR≥1.29 and ΔNLR≥0.87 were all independent risk factors of OS(all P＜0.05).Taken 1.29 and 0.87 as the best cut-off value,respectively,the area under the curve of NLRR and ΔNLR for predicting OS was 0.620 and 0.610,respectively.Conclusion NLRR and ΔNLR were helpful for predicting OS of HCC patient after the first interventional treatment.

The aim of this study was to identify the Salmonella strains isolated from an outbreak of foodborne illness in a seafood buffet restaurant and analyze their pathogenic characteristics.Epidemiological data,fecal samples from patients and chefs,and food/environmental samples from the restaurant were analyzed.Research methods included bacterial culture,serotyping,quadruple fluo-rescence PCR identification,whole-genome sequencing and antibiotic susceptibility testing.The results showed that 4 S.Java strains(serotype 1,4,12∶b∶1,2;ST42)were isolated from two outbreak cases and two sporadic cases.All isolates exhibited similar genomic features,harboring 9 virulence islands and 98 virulence genes.Antimicrobial resistance profiling revealed streptomycin monoresis-tance,mediated by aac(6′)-Iy and aac(6′)-Iaa genes.In conclusion,this event was the first reported outbreak of foodborne illness caused by S.Java in China,indicating that S.Java may be prevalent in the surveyed district.The catering industry should optimize food handling and processing procedures and enhance the surveillance of high risk pathogens.Meanwhile,further studies should ad-dress differential diagnosis and pathogenic mechanism differences between S.Java and S.paratyphi B,which will facilitate evidence-based monitoring in China.