Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

AIM:To investigate the effect of Biejiajian pill(BJJP)in reducing carbon tetrachloride(CCl4)-in-duced liver fibrosis in rats and to explore the underlying mechanism of the TLR4-NF-κB signaling pathway.METHODS:A total of 40 male Wistar rats were randomly assigned to 4 groups:control group,model group,low-dose BJJP group,and high-dose BJJP groups,with 10 rats per group.The rat model of liver fibrosis was established by intraperitoneal injection of CCl4,and two doses of BJJP(2.2 g/kg and 0.55 g/kg)were administered simultaneously.After 8 weeks of modeling and BJJP administration,the enzyme-linked immunosorbent assay(ELISA)was used to measure liver injury indicators,including alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Masson trichrome staining and Sirius red staining were performed to assess the fibrin deposition in liver tissue.Immunohistochemistry and Western blot analysis were conducted to detect the expression of extracellular matrix produced by hepatic stellate cells(HSCs).The expression of fibrosis-related proteins was examined using morphological assessment and Western blot.Finally,Western blot analysis was performed to detect the expression of proteins related to the Toll-like receptor 4(TLR4)/myeioid differentiation factor 88(MyD88)/NF-κB signaling pathway.RESULTS:The ELISA results indicated that BJJP treatment significantly re-duced ALT and AST levels in the serum of rats with liver fibrosis(P<0.01).Hematoxylin-eosin staining confirmed the protective effect of BJJP on liver tissue.Morphological analysis using Masson trichrome staining,Sirius Red staining,and alpha smooth muscle actin(α-SMA)immunohistochemical staining demonstrated that BJJP effectively reduced fibrin depo-sition in CCl4-induced rat liver fibrosis.Furthermore,the decreased expression of other markers associated with hepatic stellate cell activation,including fibronectin,collagen type Ⅰ,and α-SMA(P<0.01).Additionally,BJJP treatment sig-nificantly inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway induced by CCl4(P<0.05).CONCLU-SION:BJJP alleviates CCl4-induced liver injury and fibrosis in rats.This effect may be attributed to its inhibition of the TLR4-NF-κB signaling pathway,which subsequently suppressed the HSCs activation.

Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

AIM:To investigate the effect of Biejiajian pill(BJJP)in reducing carbon tetrachloride(CCl4)-in-duced liver fibrosis in rats and to explore the underlying mechanism of the TLR4-NF-κB signaling pathway.METHODS:A total of 40 male Wistar rats were randomly assigned to 4 groups:control group,model group,low-dose BJJP group,and high-dose BJJP groups,with 10 rats per group.The rat model of liver fibrosis was established by intraperitoneal injection of CCl4,and two doses of BJJP(2.2 g/kg and 0.55 g/kg)were administered simultaneously.After 8 weeks of modeling and BJJP administration,the enzyme-linked immunosorbent assay(ELISA)was used to measure liver injury indicators,including alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Masson trichrome staining and Sirius red staining were performed to assess the fibrin deposition in liver tissue.Immunohistochemistry and Western blot analysis were conducted to detect the expression of extracellular matrix produced by hepatic stellate cells(HSCs).The expression of fibrosis-related proteins was examined using morphological assessment and Western blot.Finally,Western blot analysis was performed to detect the expression of proteins related to the Toll-like receptor 4(TLR4)/myeioid differentiation factor 88(MyD88)/NF-κB signaling pathway.RESULTS:The ELISA results indicated that BJJP treatment significantly re-duced ALT and AST levels in the serum of rats with liver fibrosis(P<0.01).Hematoxylin-eosin staining confirmed the protective effect of BJJP on liver tissue.Morphological analysis using Masson trichrome staining,Sirius Red staining,and alpha smooth muscle actin(α-SMA)immunohistochemical staining demonstrated that BJJP effectively reduced fibrin depo-sition in CCl4-induced rat liver fibrosis.Furthermore,the decreased expression of other markers associated with hepatic stellate cell activation,including fibronectin,collagen type Ⅰ,and α-SMA(P<0.01).Additionally,BJJP treatment sig-nificantly inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway induced by CCl4(P<0.05).CONCLU-SION:BJJP alleviates CCl4-induced liver injury and fibrosis in rats.This effect may be attributed to its inhibition of the TLR4-NF-κB signaling pathway,which subsequently suppressed the HSCs activation.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.