This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVE: To explore the diagnostic value of shear wave elastography (SWE) for clinically significant prostate cancer (csPCa). METHODS: We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer (PCa) in Baoji Central Hospital from June 2017 to July 2023. All the patients underwent the following examinations in the order of serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS), measurement of the stiffness of the entire prostate gland by SWE, and TRUS-guided prostate puncture biopsy. The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base, middle, and apex of the prostate, including the maximum Young's modulus (Emax), mean Young's modulus (Emean), and minimum Young's modulus (Emin). We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results, focusing on their diagnostic performance for csPCa. RESULTS: Of the 359 cases, 189 were diagnosed by pathological puncture biopsy as BPH, 26 as non-csPCa, and 144 as csPCa. The PSA level, Emax, Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups (all P < 0.01), but showed no statistically significant difference between the BPH and non-csPCa groups (all P > 0.05). The area under the receiver operating characteristic curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Emax in the diagnosis of csPCa were 0.852, 143.92 kPa, 72.22%, 84.65%, 75.91%, 81.98% and 79.67%; those of Emean were 0.868, 82.42 kPa, 67.36%, 91.16%, 83.62%, 80.66% and 81.62%; and those of Emin were 0.682, 32.73 kPa, 47.22%, 89.30%, 73.91%, 71.54% and 72.14%, respectively. In the non-csPCa group, Emax, Emean and Emin were found below the optimal cut-off value in 73.08% (19/26), 92.31% (24/26) and 88.46% (23/26), respectively. CONCLUSION The stiffness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa, reduces unnecessary detection of non-csPCa, and provides some reference for its active surveillance.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Elasticity Imaging Techniques ; Retrospective Studies ; Prostate/pathology* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

AIM:This study explores how the combination of rapamycin(Rapa)and flagellin(FliC)affects the inhibition of 4T1 breast cancer cells.The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro.METHODS:4T1 breast cancer cells were divided into four groups:control group,Rapa group,FliC group,and Rapa+FliC group.The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry.Concurrently,the KEGG pathway of differentially expressed genes(DEGs)was analyzed by high-throughput mRNA sequencing.Furthermore,the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING.The PPI network of DEGs was then constructed,and the Hub genes were sub-sequently screened.The protein expression of the Hub gene was verified based on the HPA database.RESULTS:CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibi-tion and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone(P<0.05).Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group,predominantly in the PI3K/Akt signaling pathway.In contrast,DEGs between the FliC group and control were mainly concentrated in signaling path-ways like NOD-like receptor signaling.Additionally,150 DEGs were identified between the Rapa+FliC group and the Ra-pa group,focusing primarily on pathways such as mTOR.From the protein-protein interaction(PPI)network,ten hub genes,including Atm and Itga2,were identified.CONCLUSION:The combination of Rapa+FliC could inhibit the via-bility of 4T1 breast cancer cells in vitro and promote apoptosis,potentially through the PI3K/Akt/mTOR signaling path-way.The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Abstract: Objective To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods　The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (≤18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results　The mean nucleic acid conversion time of 228 patients was (18.7±12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2±2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8±1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P>0.05); however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P<0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P<0.05). Conclusions The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.

Objective:To investigate the predictive value of Pitt bacteremia score (PBS) on 28-day mortality of patients with extensively drug-resistant Klebsiella pneumoniae (XDR-KP) bloodstream infection.Methods:A retrospective cohort study was conducted to analyze the clinical characteristics of patients with XDR-KP bloodstream infection admitted to the Emergency Intensive Care Unit of Nanjing Drum Tower Hospital from January, 2018, to December, 2021. The patients were divided into the survival and non-survival groups according to the 28-day survival. Multivariate logistic regression analysis was performed to determine the risk factors of 28-day mortality of the patients. Receiver operating curve (ROC) curve was drawn to analyze the predictive value of PBS in 28-day mortality of patients with XDR-KP bloodstream infection. The correlations between PBS, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure (SOFA) assessment were performed using Pearson correlation coefficient. The optimal cut-off value of PBS score was used as the boundary point to group the differences between APACHE II and SOFA scores in different groups. Kaplan-Meier method was used to analyze the prognosis of patients with XDR-KP bloodstream infection.Results:A total of 118 patients (82 males and 36 females) with XDR-KP bloodstream infection, aged (65.98±15.16) years, were included in this study. The 28-day mortality was 61.02%. The PBS was significant higher in the non-survival group than in the survival group [(5.68±1.86) vs. (2.48±1.02), P=0.011]. Multivariate logistic regression analysis showed that PBS ( OR=4.940, 95% CI: 2.720-8.968, P=0.008), APACHE II score ( OR=1.630, 95% CI: 1.361-1.952, P=0.010) and SOFA score ( OR=1.879, 95% CI: 1.451-2.422, P=0.009) were independently risk factors of 28-day mortality of patients with XDR-KP bloodstream infection. The area under the ROC curve of the PBS predicting 28-day mortality was 0.970 (95% CI: 0.945-0.995, P<0.001), and the optimal cut-of value was 3.5. In addition, PBS was significantly associated with APACHE II score ( r=0.916, P<0.001) and SOFA score ( r=0.829, P<0.001). Moreover, Kaplan-Meier analysis showed that the 28-day survival rate of patients with PBS <3.5 was significantly higher than that of patients with PBS >3.5 ( P=0.001). Conclusions:PBS is a significant, independent predictor of 28-day mortality in patients with XDR-KP bloodstream infection.