Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.

Background and purpose:Owing to the reliance on computed tomography(CT)for evaluating skull-base bone invasion in nasopharyngeal carcinoma and the potential harm of ionizing radiation from CT,zero echo time magnetic resonance imaging(ZTE-MRI)offers high-resolution bone delineation without radiation exposure.Therefore,this study aimed to systematically assess the diagnostic performance of ZTE-MRI for detecting skull-base bone invasion and to explore its clinical feasibility as an alternative to CT.Methods:This prospective study collected 95 nasopharyngeal carcinoma patients treated in Fujian Provincial Cancer Hospital from April 2020 to December 2022 as the research subjects.The patients who do not meet the inclusion standards would be excluded.Using the GE Discovery 750W 3.0T MR scanner to obtain unenhanced scan and enhanced scan,using ZTE-MRI technology to obtain ZTE-MRI and CT image.The results of the imaging scans were used to independently assess skull base bone invasion by two radiologists.This study was approved by the Ethics Committee of Fujian Cancer Hospital(K2025-314-01),and informed consent from the patients were obtained.Results:A total of 80 nasopharyngeal carcinoma patients were included in the final analysis.There was a high degree of consistency between CT diagnosis of nasopharyngeal carcinoma skull base bone invasion and of gold standards,and the difference was statistically significant(κ=0.645,P＜0.001).There was a high degree of consistency between ZTE-MRI diagnosis of nasopharyngeal carcinoma skull base bone invasion and of gold standards,and the difference was statistically significant(κ=0.774,P＜0.001).There was a high degree of consistency between ZTE-MRI combined with conventional MRI diagnosis of nasopharyngeal carcinoma skull base bone invasion and gold standards,and the difference was statistically significant(κ=0.912,P＜0.001).Conclusion:ZTE-MRI technology provides"like CT"images for the skull base bone invasion in nasopharyngeal carcinoma,and ZTE-MRI technology can replace CT examination in clinical practice.

Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.

Background and purpose:Owing to the reliance on computed tomography(CT)for evaluating skull-base bone invasion in nasopharyngeal carcinoma and the potential harm of ionizing radiation from CT,zero echo time magnetic resonance imaging(ZTE-MRI)offers high-resolution bone delineation without radiation exposure.Therefore,this study aimed to systematically assess the diagnostic performance of ZTE-MRI for detecting skull-base bone invasion and to explore its clinical feasibility as an alternative to CT.Methods:This prospective study collected 95 nasopharyngeal carcinoma patients treated in Fujian Provincial Cancer Hospital from April 2020 to December 2022 as the research subjects.The patients who do not meet the inclusion standards would be excluded.Using the GE Discovery 750W 3.0T MR scanner to obtain unenhanced scan and enhanced scan,using ZTE-MRI technology to obtain ZTE-MRI and CT image.The results of the imaging scans were used to independently assess skull base bone invasion by two radiologists.This study was approved by the Ethics Committee of Fujian Cancer Hospital(K2025-314-01),and informed consent from the patients were obtained.Results:A total of 80 nasopharyngeal carcinoma patients were included in the final analysis.There was a high degree of consistency between CT diagnosis of nasopharyngeal carcinoma skull base bone invasion and of gold standards,and the difference was statistically significant(κ=0.645,P＜0.001).There was a high degree of consistency between ZTE-MRI diagnosis of nasopharyngeal carcinoma skull base bone invasion and of gold standards,and the difference was statistically significant(κ=0.774,P＜0.001).There was a high degree of consistency between ZTE-MRI combined with conventional MRI diagnosis of nasopharyngeal carcinoma skull base bone invasion and gold standards,and the difference was statistically significant(κ=0.912,P＜0.001).Conclusion:ZTE-MRI technology provides"like CT"images for the skull base bone invasion in nasopharyngeal carcinoma,and ZTE-MRI technology can replace CT examination in clinical practice.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

Purpose To study the mechanism of invasion and metastasis of hepatocellular carcinoma(HCC)based on LINC02036 expression.Methods A total of 60 pairs of the HCC tissues along matched adjacent non-tumor tissues were col-lected.The differential expression of lncRNA was confirmed by RNA sequencing.LINC02036 knockdown and overexpressing Huh7 cells were constructed in vitro,and the proliferation and invasion ability of the cells were detected by CCK-8,colony for-mation test,and Transwell method,respectively.The epithelial-mesenchymal transition(EMT)marker protein was detected by Western blot.In addition,the interaction between LINC02036 and TGF-β1 was identified by RNA pull down and mass spec-trometry(MS),which was further validated by RNA immuno-precipitation(RIP).Results It was confirmed by RNA se-quencing that LINC02036 was differentially expressed in adja-cent normal tissues and HCC tissues.High expression of LINC02036 was significantly correlated with the largest tumor size(P=0.025),advanced TNM staging(P=0.028),and micro vascular invasion(P＜0.001).In vitro experiments,overexpression of LINC02036 obviously elevated cell viability,metastasis,invasion and EMT(P＜0.05),while knockout of LINC02036 showed the opposite effects(P＜0.05).TGF-β1 was identified as a potential interactive protein and pulled down by LINC02036 in HCC cell lysates.We verified the interaction between LINC02036 and TGF-β1 by RIP assay.Moreover,acti-nomycin D assay showed that overexpression of TGF-β1 en-hanced the RNA stability of LINC02036(P＜0.05).Conclu-sion LINC02036 plays a carcinogenic effect in HCC,promotes tumor proliferation and microvascular invasion,and the related mechanism may involve the enhancement of its RNA stability by TGF-β1.

Objective:To analyze the efficacy and safety of FOLFOX-hepatic arterial infusion chemotherapy (HAIC) combined with targeted immunotherapy for initial unresectable hepatocellular carcinoma.Methods:A retrospective analysis was conducted on the data of initial unresectable hepatocellular carcinoma patients who visited Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2022 to June 2023. A total of 51 patients were enrolled, including 47 males and 4 females, with the age of (56.1±10.7) years. All 51 patients received HAIC combined with immune targeted therapy. After each HAIC combined with immune targeted therapy, the efficacy was evaluated according to the modified response evaluation cirteria in solid tumor (mRECIST). Objective response rate and disease control rate were calculuted. The conversion surgery rate and adverse events during treatment were recorded. Follow up patients' disease progression and survival status, and meanwhile analyze prognosis.Results:According to mRECIST assessment, the number of patients with complete remission, partial remission, disease stability, and disease progression were 4 (7.8%), 27 (52.9%), 14 (27.4%), and 6 (11.8%), respectively. The disease remission rate was 60.8%(31/51), and the disease control rate was 88.2%(45/51). After HAIC combined with immune targeted therapy, 13 patients underwent liver cancer resection, with a surgical conversion rate of 25.5%(13/51). The median progression free survival of 51 patients was 14.2 months, and the median overall survival has not yet been reached. The progression free survival rates of 51 patients at 6 and 12 months were 90.2% and 64.7%, respectively, and the cumulative survival rates at 6 and 12 months were 100% and 86.3%, respectively. During the treatment period, all patients experienced various degrees of adverse reactions, 38(75.5%) patients were grade 1-2 adverse accidents, which could be relieved and controlled after corresponding treatment.Conclusion:FOLFOX-HAIC combined with targeted immunotherapy provides an effective and safe treatment option for unresectable hepatocellular carcinoma, offering surgical resection opportunities for unresectable hepatocellular carcinoma patients.

Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P＜0.001), and between half a year after surgery and before discharge after surgery (P＜0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective To investigate the incidence of central obesity and characteristics and changing trend of macronutrient energy supply in adult residents of Chongqing, and to analyze the relationship between carbohydrate energy supply and central obesity. Methods Using the longitudinal tracking data of China Health and Nutrition Survey project, combined with China food composition table , the energy and nutrient intake and macronutrient energy supply ratio were calculated. The association between carbohydrate energy supply and central obesity was analyzed by multi-level statistical model. Results In 2011, 2015 and 2018, the carbohydrate supply ratio of adult residents in Chongqing was 43.02%, 46.52%, and 46.07%, respectively, and the difference was statistically significant (F=18.699, P<0.001). The overweight rates in 2011, 2015, and 2018 were 29.2%, 36.7%, and 37.8%, while the obesity rates were 12.2%, 13.5%, and 19.5%, respectively, with statistically significant differences (χ²=41.416, P<0.001). The central obesity rates were 51.5%, 57.2%, and 62.8%, respectively (χ²=21.008, P<0.001). The carbohydrate supply ratio was positively correlated with waist circumference. Compared to the population with a carbohydrate to energy ratio of <55%, the risk of central obesity in the population with a carbohydrate to energy ratio of ≥ 65% was 1.63 times higher. Conclusion The ratio of carbohydrate to energy supply of adult residents in Chongqing has slightly increased. Rates of overweight, obesity and central obesity are on the rise. A high carbohydrate to energy supply ratio may be a risk factor for central obesity.