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 traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

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*

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Objective To explore the value of 18F-FDG PET/CT dynamic imaging in the diagnosis of primary liver cancer and liver metastases.Methods In this study, the data of 94 patients with hepatic malignant lesions [hepa-tocellular carcinoma group (25 cases) , cholangiocellular carcinoma group (27 cases) , and liver metastases group (42 cases) ] imaged by whole-body dynamic 18 F-FDG PET/CT were used as the research subjects, and the meth-ods of (ANOVA) and subjects' working characteristic curves (ROC) were applied to examine the patients with liv-er malignant tumours of different pathological types SUVmax, MRFDG, TBR and dmax were statistically analysed as im-aging features.Results Among 94 patients, the differences in SUVmax, MRFDG, TBRSUVmax and TBRMRFDG were sta-tistically significant in the hepatocellular carcinoma, cholangiocellular carcinoma and hepatic metastasis groups (SUVmax: F =48.773, P <0.001; MRFDG: F =26.334, P <0.001; TBRSUVmax: F =41.314, P <0.001;TBRMRFDG:F=20.821, P<0.001).The AUCs for the differential diagnosis of primary hepatocellular carcinoma and hepatic metastases for SUVmax, MRFDG, TBRSUVmax, and TBRMRFDG were 0.836, 0.851, 0.827, and 0.847, re-spectively.There was a positive correlation between SUVmax, MRFDG, and the hepatic malignant lesions' There was a positive correlation between SUVmax, MRFDG and the maximum diameter dmax(SUVmax:r=0.4, P<0.05;MRFDG:r=0.2, P<0.05), and the difference was statistically significant.Conclusion 18F-FDG PET/CT dynamic ima-ging has good differential diagnostic efficacy in different pathological types of liver malignant tumors.There is a pos-itive correlation between SUVmax, MRFDG and dmax in different pathological types of liver malignant tumors.

Objective　To analyze the drug resistance, genomic information, and genetic relationships of Extended-Spectrum β-Lactamases (ESBLs)-positive Acinetobacter strains colonized in the intestinal tract of children with and without diarrhea, and to explore the carrying status and distinguishing features of two group ESBLs-positive Acinetobacter strains. Methods　A total of 842 fresh fecal samples were collected from children with and without diarrhea from a hospital in Shanghai, 2017-2019. ESBLs-resistant Acinetobacter strains were isolated and identified, followed by a drug sensitivity test and whole genome sequencing. A phylogenetic tree was constructed to explore the genetic relationship between Acinetobacter baumannii strains in this study and those isolated in China during the same period. Results　A total of 13 ESBLs-positive Acinetobacter strains were isolated, including 11 strains in the diarrhea group and two strains in the non-diarrhea group, the positive rate of ESBLs strains in the diarrhea group was significantly higher than that in the non-diarrhea group (χ2=5.206, P=0.023). All strains showed a high resistance rate to the first-generation cephalosporins (100.0%) and the second-generation cephalosporins (100.0%), with a multidrug resistance rate of 53.8% (7/13). There was no significant difference in the rates of resistance to individual antibiotics and multidrug resistance between the two groups (P>0.05). The blaOXA resistance gene was carried by all strains on the chromosome, which encode enzymes that hydrolyze clinically important antibiotics such as third-generation cephalosporins and carbapenems. Adhesion-type virulence genes were carried by 92.3% (12/13) of the strains, and secretion-type virulence genes were present in 84.6% (11/13). Furthermore, 92.3% (12/13) of ESBLs-positive Acinetobacter strains carried plasmids, with one A. baumannii strain isolated from a non-diarrhea child carrying seven types of plasmids. The analysis of the phylogenetic relationship indicated that A. baumannii strains isolated in this study formed a clonal cluster, and also clustered with some strains from southern China during the same period. Conclusions　ESBLs-positive Acinetobacter strains isolated from children with and without diarrhea exhibited serious drug resistance, carrying multiple resistance and virulence genes, as well as multiple plasmids. Carrying multiple plasmids may facilitate the horizontal transmission risk of drug-resistance genes and virulence genes, indicating the need to pay attention to the characteristics of intestinal colonized ESBLs-positive Acinetobacter strains in children and strengthen the monitoring of drug-resistant bacteria colonized in the intestine in healthy children.

OBJECTIVE: Our study aimed to conduct genomic characterization of Salmonella strains carrying the bla _NDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes. METHODS: We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the bla _NDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer. RESULTS: We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying bla _NDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that bla _NDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission. CONCLUSION This study marks the first detection of bla _NDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying bla _NDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
beta-Lactamases/genetics* ; Plasmids/genetics* ; Humans ; Anti-Bacterial Agents/pharmacology* ; China ; Microbial Sensitivity Tests ; Salmonella typhimurium/isolation & purification* ; Salmonella/isolation & purification* ; Salmonella Infections/microbiology*

ObjectiveTo construct a traditional Chinese medicine （TCM） syndrome diagnosis and prescription model for coronary heart disease with the improved Transformer algorithm. MethodTaking the syndrome elements of coronary heart disease as key links， the model was constructed based on the clinical diagnosis and treatment principle of "symptoms-syndrome elements-syndrome-treatment method-prescription-medicine （dose）". The basic logic of improved Transformer algorithm was constructed with multi-head attention mechanism， compound term vector and dropout， in order to form the model with functions of TCM syndrome elements judgment， syndrome diagnosis， prescription recommendation. After the model was constructed， it was trained by 8 030 cases. And 100 cases with TCM prescriptions were randomly selected for testing， and the model output prescriptions were compared with those of clinicians for qualitative evaluation of the model. ResultThe improved Transformer with multi-head attention improved the accuracy of the model. The model was consistent with clinicians in the judgment of main syndromes and the selection of prescriptions. Whereas there was a certain room for improvement in the addition and subtraction of medicines. ConclusionThe improved Transformer model can improve the accuracy and stability of output， which is an embodiment of the intelligent development of TCM.

ObjectiveTo construct the syndrome differentiation and treatment process in the diagnosis and treatment guideline into a visual knowledge graph using knowledge graph technology， and visualize the process from the input of clinical manifestations to the output of corresponding traditional Chinese medicine （TCM） diagnosis and prescriptions through programs， to visually display the diagnosis and treatment process as well as the data relationship for TCM practitioners. This paper facilitated the standardized and normalized TCM diagnosis and treatment of coronary heart disease， and provided technical support for the inheritance and promotion of TCM diagnosis and treatment. MethodNeo4j and py2neo were used to construct a knowledge graph based on the Guideline for Diagnosis and Treatment of Coronary Heart Disease with Stable Angina Pectoris published by China Association of Chinese Medicine Cardiovascular Disease Branch. A knowledge graph regarding the input of clinical manifestations was built through programs， visually displaying the standardized TCM diagnosis and treatment process of coronary heart disease with stable angina pectoris. ResultThe structured data were extracted from the guideline by py2neo connecting to Neo4j and imported into Neo4j to construct the knowledge graph of TCM diagnosis and treatment of coronary heart disease with stable angina pectoris， which had graph database query function. ConclusionAiming at the problems existing in the inheritance of TCM diagnosis and treatment， this paper proposed a diagnosis and treatment guideline integrating the experience of TCM experts and evidence-based evidence for coronary heart disease with stable angina pectoris， and realized the visualization process of knowledge graph based on TCM diagnosis and treatment guideline and the experience of TCM experts. It is helpful to intuitively display the whole TCM diagnosis and treatment process from symptom input to prescriptions and inherit TCM experience， providing a new paradigm for standardized and normalized TCM diagnosis and treatment.