Objective To explore the risk factors for myocardial injury in esophagogastric variceal bleeding(EGVB)patients with liver cirrhosis during hospitalization.Methods A case-control trial was conducted on 235 EGVB patients admitted to our hospital between May 2021 and July 2022.Their basic information,laboratory results and relevant data during hospitalization were collected.According to their myocardial enzyme profiles during hospitalization,they were divided into myocardial injury group(n=46)and non-myocardial injury group(n=189).Univariate regression analysis and clinical correlation analysis were used to preliminarily screen the risk factors for myocardial injury secondary to EGVB caused by liver cirrhosis.Then,multivariate logistic regression analysis was used to further screen the risk factors.A nomogram was constructed based on the selected risk factors and the occurrence of myocardial injury.Receiver operating characteristic(ROC)curve was plotted to analyze the independent predictive value of these factors alone or combined together.Calibration curve analysis and internal verification were utilized to evaluate the predictive performance of the nomogram model.Subgroup verification was performed in the myocardial infarction group.Results Univariate analysis revealed that statistical differences were observed in age,sex,hypertension,renal disease,underlying diseases,vomiting,leukocytosis,increased alanine aminotransferase(ALT)or aspartate aminotransferase(AST),albumin,red blood cell hematocrit(HCT),international normalized ratio(INR),endoscopy within 6 h after admission,and Child-Pugh(CP)class between the myocardial injury group and the non-myocardial injury group(P＜0.01).Multivariate logistic regression analysis showed that age(P=0.014,OR=1.153,95％CI:1.030～1.291),underlying diseases(P=0.005,OR=1.122,95％CI:1.032～2.437),and albumin(P=0.012,OR=0.449,95％CI:0.241～0.837)were independent risk factors for inhospital myocardial injury in EGVB patients with liver cirrhosis.The AUC value of the above indicators combined together for predicting myocardial injury was 0.902.Hosmer-Lemeshow test and calibration curve analysis indicated that the nomogram had good prediction consistency(Chi-square=12.88,P=0.615).Internal verification correctly distinguished 86.4％of verification objects.Subgroup analysis of myocardial injury patients showed that albumin was also an independent risk factor for in-hospital myocardial injury in this population(AUC=0.80).Conclusion Age,underlying diseases,and albumin level are independent risk factors for in-hospital myocardial injury in EGVB patients with liver cirrhosis.Albumin level can be used as an independent risk factor for predicting myocardial infarction.Combination of the above 3 indicators has a high diagnostic value in early identification and prevention of myocardial injury in this patient population.

Gastric cancer is a common malignant tumor with complex pathological mechanisms， a low early diagnosis rate， and a high mortality rate. However， surgical treatment， targeted therapy， and chemotherapy have their treatment limitations and toxic side effects. Therefore， exploring the pathogenesis and mechanism of gastric cancer and finding effective treatment methods are important. At present， researches has found that tumor epithelial cells exhibit individual differences in molecular characteristics and exhibit metabolic heterogeneity that affects cell phenotype and function. The interaction between metabolites and cytokines can inhibit the formation of the tumor immune microenvironment and promote malignant progression. Therefore， metabolic reprogramming is regarded as a key feature of tumors and plays an important role in the process of tumor occurrence and development. However， the continuous deterioration of gastric cancer may be closely related to changes in the energy metabolism of cancer cells. Gastric cancer cells may regulate the dysregulation of synthesis or decomposition pathways such as glucose metabolism， amino acid metabolism， lipid metabolism， and nucleotide metabolism and activate associated signaling pathways， key proteins， and genes， leading to proliferation， invasion， and metastasis of cancer cells. In recent years， there has been a close relationship between the effective intervention by traditional Chinese medicine in gastric cancer and the regulation of metabolic reprogramming. There has been some progress in the intervention research on effective ingredients and formulas of traditional Chinese medicine for cancer. This article summarized existing Chinese and foreign literature on how gastric cancer cells affect disease progression by regulating their related metabolic networks， such as glucose metabolism， amino acid metabolism， lipid metabolism， and nucleotide metabolism， as well as how effective ingredients and formulas of traditional Chinese medicine enhance anti-tumor effects through targeted metabolism. It reviewed metabolic reprogramming intervention in gastric cancer， providing a reference for research on metabolic reprogramming regulation by traditional Chinese medicine and new targets and strategies for the treatment and prognosis of gastric cancer.

Objective To investigate the effect of different timing of endoscopic intervention on the short-term prognosis of patients with cirrhosis combined with esophageal and gastric variceal bleeding(EGVB),as well as to analyze the independent related factors affecting 6-week mortality of patients with EGVB and to construct a prediction model.Methods The patients with EGVB admitted to Renmin Hospital of Wuhan University for emergency endoscopic intervention from June 2021 to December 2023 were consecutively included.According to the timing of endoscopic intervention,they were categorized into the urgent endoscopy group(within 6 hours after the consultation,n=94)and the early endoscopy group(6-24 hours after the consultation,n=76).All the enrolled patients underwent a 6-week postoperative follow-up.The propensity score matching(PSM)was used as 1∶1,and baseline characteristics before and after PSM,operation related information,short-term prognosis,etc.after PSM between the two groups were compared.The binary logistic regression was used to analyze the factors influencing the 6-week mortality of patients with EGVB.A nomogram model based on the independent related factors were constructed,and ROC,calibration,and decision curves were used to verify the prognostic value of the model.Results There were significant differences in the model of end-stage liver disease(MELD)score,total bilirubin level,propotions of patients with systolic blood pressure＜90 mmHg,diabetes mellitus or initial bleeding event between the two groups(P＜0.05).After PSM,a total of 106 patients met the criteria.There was no significant difference in baseline date,operation related information,complications after operation,and 6-week mortality rate after operation between the two groups with 53 patients in each group after PSM.Blood product consumption was significantly higher in the urgent endoscopy group than that in the early endoscopy group(P=0.046).The binary logistic regression analysis results showed that initial bleeding,higher Charson comorbidity index(CCI)score,active bleeding and longer duration of surgery were independent related factors for 6-week mortality after operation in patients with EGVB(P＜0.05),whereas timing of endoscopic intervention was not a related factor for 6-week mortality.A nomogram model was constructed and AUC of the model was 0.790,with higher accuracy and utility.Conclusions The association of endoscopic intervention timing with 6-week mortality after operation in patients with EGVB is not significant obvious;the prognostic value of the model basing on initial bleeding,CCI score,active bleeding and surgery duration is higher for 6-week mortality after operation in patients with EGVB.

Objective:To explore the independent risk factors of portal vein thrombosis (PVT) in liver cirrhosis, and to establish and evaluate a risk prediction model for PVT in patients with cirrhosis.Methods:A total of 295 cases of cirrhosis hospitalized in Renmin Hospital of Wuhan University from December 2019 to October 2021 were divided into a modeling set ( n=207) and an internal validation set ( n=88) by the random number table. In addition, patients with cirrhosis hospitalized in Yichang Central People's Hospital, Wuhan Puren Hospital, No.2 People's Hospital of Fuyang City and People's Hospital of China Three Gorges University during the same period were collected as an external validation set ( n=92). The modeling set was divided into PVT group ( n=56) and non-PVT group ( n=151). Univariate analysis was used to preliminarily screen the related indicators of PVT, and then multivariate logistic regression analysis with forward stepwise regression was used to determine independent risk factors for PVT. A nomogram prediction model was constructed based on the independent risk factors obtained. The internal and external validation set were used to verify the predictive ability of the model. Distinction degree was used to evaluate the ability of the model to distinguish patients with or without PVT. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the consistency between predicted risk and the actual risk of the model. Results:Univariate analysis showed that smoking, history of splenectomy, trans-jugular intrahepatic portosystemic shunt (TIPS), gastrointestinal bleeding and endoscopic variceal treatment, and levels of hemoglobin, alanine aminotransferase, aspartate aminotransferase and D-dimer were significantly different between the PVT group and the non-PVT group ( P<0.05). Multivariate logistic regression analysis found that smoking ( P=0.020, OR=31.21, 95% CI: 1.71-569.40), levels of D-dimer ( P=0.003, OR=1.12, 95% CI: 1.04-1.20) and hemoglobin ( P=0.039, OR=0.99, 95% CI: 0.97-1.00), history of TIPS ( P=0.011, OR=18.04, 95% CI: 1.92-169.90) and endoscopic variceal treatment ( P=0.001, OR=3.21, 95% CI: 1.59-6.50) were independent risk factors for PVT in patients with liver cirrhosis. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the internal validation set was 0.802 (95% CI: 0.709-0.895) ( P<0.001), and the AUC for the external validation set was 0.811 (95% CI: 0.722-0.900) ( P<0.001). Both AUC were larger than 0.75. The calibration curve of Hosmer-Lemeshow goodness-of-fit test showed that the P values of both internal validation set ( χ2=3.602, P=0.891) and the external validation set ( χ2=11.025, P=0.200) were larger than 0.05. Conclusion:Smoking, history of TIPS or endoscopic variceal treatment, levels of D-dimer and hemoglobin are independent risk factors for PVT in patients with liver cirrhosis. The prediction nomogram model based on the above factors has strong predictive ability.

Objective:To evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt.Methods:Data of 24 patients with gastric fundal varices with large spontaneous shunt (the smallest diameter was 5-15 mm) treated by EUS-guided coil embolization combined with endoscopic cyanoacrylate injection in Renmin Hospital of Wuhan University from December 2016 to December 2020 were retrospectively analyzed. The short-term efficacy (the rates of technical success, five-day rebleeding and six-week mortality) and long-term efficacy (the rates of one-year rebleeding, one-year mortality and three-year mortality) and safety (ectopic embolism) were evaluated.Results:The technical success rate was 91.7% (22/24), and the five-day rebleeding rate was 0 (0/22). Computed tomography angiography of portal vein reexamined 2 days after the treatment showed embolism of splenic vein in 1 patient (4.5%). The median follow-up time was 14.9 months (ranging 1.0-48.6 months) and 2 patients were lost during follow-up. The six-week mortality was 0 (0/20), and the one-year rebleeding rate was 35.0% (7/20). Among 12 patients who underwent endoscopy in the follow-up, 5 had aggravation of esophageal varices, and 5 had aggravation of portal hypertension gastropathy. The one-year and three-year mortalities were 5.0% (1/20) and 20.0% (4/20), respectively, neither of which was related to such events as bleeding or ectopic embolism.Conclusion:EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt is effective and safe in short term, with a low rate of ectopic embolism. Long-term efficacy and safety need to be further confirmed.

As a member of the transient receptor potential ion channel family, transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel and is widely distributed in a variety of tissues and organs. In recent years, more and more studies have shown that TRPV4 channel proteins are closely associated with liver diseases such as liver fibrosis, liver cancer, and polycystic liver disease. This article analyzes the articles on TRPV4 and liver disease and summarizes the exact signaling pathways and possible potential mechanism between TRPV4 and liver disease, so as to provide new ideas for clinical application and further studies.

Terpenoids are a group of structurally diverse compounds with good biological activities and versatile functions such as anti-cancer and immunity-enhancing effects, and are widely used in food, healthcare and medical industries. Facilitated by the increasing understandings on the natural biosynthetic pathways of terpenoids in recent years, Saccharomyces cerevisiae has been engineered into high-yield strains for production of a variety of terpenoids, some of which have reached or become close to the level required by industrial production. In this connection, synthetic biology driven biotechnological production of terpenoids has become a promising alternative to chemical synthesis and traditional extraction approaches. This article summarizes the recent process in engineering S. cerevisiae for terpenoids biosynthesis, highlighting the effect of synthetic biology strategies by taking a couple of typical terpenoids as examples.
Biosynthetic Pathways ; Metabolic Engineering ; Saccharomyces cerevisiae/genetics* ; Synthetic Biology ; Terpenes

Objective:To investigate the optimal emergency endoscopy timing in patients with esophagogastric variceal bleeding (EGVB).Methods:The clinical data of patients with EGVB emergency endoscopy in Renmin Hospital of Wuhan University from December 2018 to November 2020 were collected and analyzed. According to the time interval from admission to the start of emergency endoscopy, they were divided into emergency endoscopy group (<6 h, n=115) and early endoscopy group (6-24 h, n=57). The baseline data, clinical efficacy and postoperative situation of the two groups were compared, and the risk factors of 6-week mortality of EGVB emergency endoscopy were analyzed by univariate and multivariate analysis. Results:In terms of baseline characteristics, there were no significant differences in age, gender, causes, shock index, model for end-stage liver disease (MELD) score, charlson complication index (CCI) score, portal hypertension related complications between the two groups ( P<0.05). However, the albumin (ALB) in emergency endoscopy group was significantly lower than that in early endoscopy group ( P<0.001). There were significant differences in Child Pugh grading and Child Pugh score between the two groups ( P=0.002, P=0.001). In terms of endoscopic efficacy, the detection rate of bleeding site in emergency endoscopy group was significantly higher than that in early endoscopy group (90.4% and 73.7%, P<0.05). There was no significant difference in operation duration, immediate hemostasis success rate, 5-day rebleeding rate, rescue treatment demand and 6-week mortality between the two groups ( P>0.05). There was no significant difference in bleeding related death between the two groups ( P>0.05). In addition, there was no significant difference in blood product consumption, intensive care unit (ICU) stay and total hospital stay between the two groups ( P>0.05). Multivariate analysis showed that Child Pugh grade C ( P=0.018), MELD score ( P=0.005) and CCI score ( P=0.001) were independent risk factors for 6-week death outcome of EGVB patients, while emergency endoscopic intervention time was not related to 6-week death outcome ( P=0.5). Conclusions:The efficacy of early endoscopic intervention is no worse than that of emergency endoscopic intervention, except for the identification of bleeding site. Child-Pugh grade C, MELD score, and CCI score are the independent risk factors for 6-week mortality, while the timing of emergency endoscopy is not associate with 6-week mortality in EGVB patients.

Objective:To evaluate the efficacy and safety of lactulose combined with polyethylene glycol for bowel preparation before colonoscopy in patients of different risks.Methods:A total of 208 patients undergoing colonoscopy were enrolled, including 108 high-risk and 100 low-risk patients. The high-risk patients were divided into group A (54 taking lactulose + polyethylene glycol) and group B (54 taking polyethylene glycol), and the low-risk patients were divided into group C (49 taking lactulose + polyethylene glycol) and group D (51 taking polyethylene glycol). The Boston bowel preparation score, cecal intubation time, withdrawal time, the detection rate of colonic polyps and adenoma, and the incidence of adverse reactions were observed.Results:Among the high-risk patients, the Boston bowel preparation score and adenoma detection rate in group A [(6.35±1.15) scores, 46.3%] were significantly higher than those in group B [(5.76±0.89) scores, 22.2%, both P<0.05], and the first defecation interval in group A was significantly shorter than that in group B [(1.20±0.85) h VS (3.29 ± 2.93) h, P<0.05]. There was no significant difference in adequate bowel preparation rate, polyp detection rate, frequency of defecation or incidence of adverse reactions between group A and B. In the low-risk patients, the first defecation interval in group C was significantly shorter than that in group D [(1.65 ± 1.35) h VS (3.42 ± 2.64) h, P<0.05], and the incidence of adverse reactions was significantly lower than that in group D (44.9% VS 64.7%, P<0.05). There was no significant difference in adequate bowel preparation rate, Boston bowel preparation score, adenoma detection rate, polyp detection rate or frequency of defecation between group C and D. Conclusion:For the high-risk patients, the effect of lactulose combined with polyethylene glycol for bowel cleansing is better than that of traditional polyethylene glycol in the improvement of the Boston bowel preparation score, adenoma detection rate, and the first defecation interval. For low-risk patients, lactulose combined with polyethylene glycol regimen has few advantages over traditional polyethylene glycol regimen.