ObjectiveTo explore the possible mechanism of Modified Gegen Qinlian Decoction （加味葛根芩连汤， MGQD） in the treatment of ulcerative colitis （UC） based on intestinal mucus barrier. MethodsThirty C57BL/6 mice were randomly divided into a control group， a model group and a MGQD group with 10 mice in each. Dextran Sulfate Sodium Salt （DSS） was used to construct the UC model in all groups except for the control group. Meanwhile， mice in the MGQD group were given 20 g/kg of MGQD decoction by gavage according to their body weight， while those in the control group and model group were given 0.2 ml/20 g of pure water by gavage， once a day for 7 consecutive days. On the day following the last gavage， the body weight， disease activity index （DAI） score， spleen weight， and colon length were compared. The pathological changes of the intestinal mucosal tissues were observed by HE staining； the protein expression levels of mucin 2 （MUC2） and leucine-rich repeat G protein-coupled receptor 5 （Lgr5） in the intestinal mucosal tissues were detected by immunofluorescence； the cuprocytes in the intestinal mucosal tissues were detected by AB/PAS staining； and the expression level of Ki67 in the intestinal mucosal tissues was detected by immunohistochemistry. ResultsHE staining showed that the colon mucosal tissue of the mice in the control group was intact. In the model group， the colon mucosal epithelial structure was severely damaged， with a large amount of inflammatory cell infiltration in the mucosal propria. In the MGQD group， the mucosal tissue structure was partially lost， with a small amount of inflammatory cell infiltration.The body weight and colon length of mice in the model group decreased significantly compared to those in the control group， while DAI scores and spleen weight increased， and the levels of MUC2， Ki67， Lgr5 proteins， and the number of goblet cells were significantly reduced （P＜0.01）. Compared to the model group， the MGQD group had increased body weight of mice， colon length， and decreased DAI scores and spleen weight； the levels of MUC2， Ki67， Lgr5 proteins， and the number of goblet cells were increased （P＜0.05 or P＜0.01）. ConclusionMGQD has a favorable ameliorative effect on UC-related symptoms and pathological tissue damage， and its mechanism of action may be related to the restoration of the prolife-ration and differentiation of intestinal stem cells into goblet cells， thereby promoting the repair of the intestinal mucus barrier.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

ObjectiveTo analyse the current implementation status of Chinese herbal medicine （CHM） placebo and systematically evaluate the placebo effect in randomised controlled trials （RCTs） of traditional Chinese medicine （TCM） for the treatment of functional dyspepsia （FD）. MethodsA combination of medical subject terms and free words was used to search six databases， including PubMed， EMBASE， Cochrane Library， Web of Science， China National Knowledge Infrastructure， and Wanfang， for RCTs with CHM placebo group for FD published from January 31st， 1994 to September 30th， 2023. The dosage forms， composition， and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool， and meta-analysis was performed on the CHM placebo response rate of patients with FD， and subgroup analysis and meta-regression was performed according to diagnostic criteria， efficacy criteria， duration of treatment， type of placebo， whether it contained active ingredient， and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants， of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation， accounting for 71% （24/34）； 32.35% （11/34） of the studies added real CHM to the placebo， and only 12 （35%） of the studies described appearance， odour， and taste. The placebo response rate in FD patients in the placebo group was 41% （95% CI： 0.35 to 0.47； P＜0.01， I² = 87%）； there was significant difference between groups with different diagnostic criteria and different treatment durations （P＜0.05 or P＜0.01）， but there was no significant difference between the different efficacy evaluation criteria， the different placebo preparation， the presence of a low-dose active ingredient， and the presence or absence of placebo assessment （P＞0.05）. ConclusionThere was a significant CHM placebo effect in patients with FD， with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients， and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos， and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.

ObjectiveTo investigate the possible mechanism of modified Gegen Qinlian Decoction （葛根芩连汤） in treatment of ulcerative colitis （UC） from the view of intestinal mucosal epithelial barrier damage and epithelial mesenchymal transition. MethodsSixty male C57BL/6J mice were divided into blank group， model group， western medicine control group， and low-， medium-， and high-dose modified Gegen Qinlian Decoction groups， with 10 mice in each group. Except for the blank group， 3% dextran sodium sulfate （DSS） was used to induce colitis model by free drinking for 7 days， and on the first day of modelling， 6， 12， and 24 g/（kg·d） of modified Gegen Qinlian Decoction were given to the low-， medium-， and high-dose groups respectively， 5-aminosalicylic acid （5-ASA） 100 mg/（kg·d） given by gavage to western medicine control group， and 10 ml/kg distilled water were given to blank and model group by gavage， once a day for 7 days. Body mass of mice was recorded and disease activity index （DAI） scores were performed daily. The mice were anesthetized after 24h of the last administration and the colon was taken to observe the length of colon， HE staining was applied to observe the damage of colonic mucosa and score pathological states， Masson staining to detect the deposition of colonic collagen fibers， immunofluorescence to observe the distribution of F-actin in colonic mucosal epithelium， and immunohistochemistry to detect the expression of tight junction protein ZO-1， Occludin， E-cadherin and Vimentin. ResultsCompared with the blank group at the same time， the percentage of body mass of mice in the model group on day 7 of modelling significantly reduced and the DAI score was significantly increased （P＜0.01）； compared with the model group at the same time， the body mass of mice in the western medicine control group and all of modified Gegen Qinlian Decoction groups decreased， and the DAI scores of mice in the western medicine control group and the high-dose modified Gegen Qinlian Decoction group decreased （P＜0.05 or P＜0.01）； compared with the same time of mice in the low-dos Gegen Qinlian Decoction group， the body mass of mice in the high-dose Gegen Qinlian Decoction group and the western medicine control group significantly elevated （P＜0.05）. Compared with the blank group， the length of the colon of mice in the model group was significantly shortened， the pathological score and the percentage of collagen area were significantly increased， the average fluorescence intensity of F-actin was reduced， the protein levels of ZO-1， Occludin and E-cadherin in the colon tissue decreased， and the protein level of Vimentin elevated （P＜0.01）. Compared with the model group， the length of colon significantly increased， patholo-gical score， collagen area percentage decreased， ZO-1， Occludin， E-cadherin protein levels increased and Vimentin levels decreased in all medicated groups； the average fluorescence intensity of F-actin increased in the western medicine control group and the middle- and high-dose Gegen Qinlian Decoction groups （P＜0.05 or P＜0.01）. Compared with the low-dose Gegen Qinlian Decoction group， the proportion of collagen fibre area in the middle-dose Gegen Qinlian Decoction group and the western medicine control group reduced； the mean fluorescence intensity of F-actin increased in the middle-dose Gegen Qinlian Decoction group； the protein levels of ZO-1 and E-cadherin increased in the western medicine control group， and the protein levels of ZO-1 increased in the high-dose Gegen Qinlian Decoction group （P＜0.05）. Compared with the medium-dose Gegen Qinlian Decoction group， the protein levels of ZO-1 elevated in the high-dose Gegen Qinlian Decoction group （P＜0.05）. Comapred with the high-dose Gegen Qinlian Decoction group， level of E-cadherin and Vimentin protein of the western medicine control group increased （P＜0.05）. ConclusionModified Gegen Qinlian Decoction was able to reduce colonic inflammation and mucosal barrier damage and inhibit the process of epithelial mesenchymal transition in mice models of ulcerative colitis， which may be one of its action mechanisms .

OBJECTIVE To distinguish Anoectochilus roxburghii and relative species by near infrared(NIR) spectroscopy combined with chemometrics, and to establish a prediction model for rapid determine polysaccharides contents in Anoectochilus roxburghii. METHODS The NIR spectroscopy of Anoectochilus roxburghii, Anoectochilus formosanus Hayata and Ludisia discolor were collected. The prepossessing of original spectrum was optimization through accuracy of classification in the NIR model, and six supervised pattern recognition algorithms such as decision tree, K-nearest neighbor algorithm, random forest, partial least squares regression discriminant analysis, linear discriminant analysis and support vector machine(SVM) were applied to identify effect of the classification effect, optimum algorithm and then establish qualitative model. The content of polysaccharides in 76 batches of Anoectochilus roxburghii samples were examined by ultraviolet visible spectrophotometry combined with phenol sulfuric acid method. In order to select optimization algorithm, six quantitative stoichiometry algorithms consisted of SVM, extreme learning machines, decision trees, random forests, principal component regression and partial least squares regression(PLS) were used to connect polysaccharide content and the NIR spectroscopy in Anoectochilus roxburghii respectively. The best method for determining the content of Anoectochilus roxburghii polysaccharides was further optimized by spectra pretreatment, band selection and number of band variables based on successive projection algorithm(SPA). RESULTS The NIR discriminant analysis model was established by SVM with SNV+SG+2ndD, and the classification accuracy was best. The prediction performance was evaluated based on the radial basis kernel function algorithm combined with confusion matrix and ROC curve, and the model performance was good. In addition, the quantitative analysis model was constructed by continuous projection-partial least squares by the prepossessing of SNV+SG+2ndD and the optimal band of 7 000-4 000 cm-1 with 97 of variables number. The accuracy was 0.992, which was the highest. The root mean square error calibration set, correlation coefficient of calibration set, and the root mean square error in validation set, correlation coefficient of validation set were 0.625, 0.993, 0.767, 0.992, separately. The prediction deviation was 8.467, and relative deviation of prediction set was less than 10%. CONCLUSION The established NIR-SVM qualitative model and SPA-PLS quantitative model are accurate and reliable, which are enable to identify Anoectochilus roxburghii and determine polysaccharide content nondestructively. It is a new and promising method for rapid evaluation of Anoectochilus roxburghii quality.

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

ObjectiveTo investigate the clinical application value of early enteral nutrition after laparoscopic hepatectomy for hepatocellular carcinoma (HCC).MethodsA total of 49 patients with HCC undergoing laparoscopic hepatectomy in Sun Yat-sen Memorial Hospital of Sun Yat-sen University between November 2013 and June 2014 were included in this prospective study. These patients were divided into the enteral nutrition group and the parenteral nutrition group according to the random number table method. Twenty-five patients were divided into the enteral nutrition group, among them, 20 were males and 5 were females with the average age of (49±17) years old. Twenty-four patients were divided into the parenteral nutrition group, among them, 18 were males and 6 were females with the average age of (51±14) years old. The informed consents of all patients were obtained and the local ethical committee approval had been received. The patients in the enteral nutrition group were given Ensure nutrient solution orally 24 h after operation for 7 d and the patients in the parenteral nutrition group were given parenteral nutrition 24 h after operation for 7 d. The total human albumin supplemented volume, recover time of gastrointestinal function, length of hospital stay after operation and hospitalization expenses of the two groups were compared. The nutritional support associated complications were observed. The data of the two groups were compared usingt test or Wilcoxon rank-sum test.ResultsThe total human albumin supplemented volume after operation of the enteral nutrition group was (40±11) g, which was signiifcantly lower than (45±10) g of the parenteral nutrition group(t=-16.089,P<0.05). The recovery time of gastrointestinal function after operation of the enteral nutrition group was (25±8) h, which was signiifcantly shorter than (43±11) h of the parenteral nutrition group (t=-36.928,P<0.05). The length of hospital stay after hepatectomy of the enteral nutrition group was (8±2) d, which was signiifcantly lower than (10±3) d of parenteral nutrition group (t=-12.025,P<0.05). The total hospitalization expenses of the enteral nutrition group were RMB 45,000 (37,000-61,000) yuan, which were signiifcantly lower than RMB 49,000 (42,000-67,000) yuan of the parenteral nutrition group (Z=-18.495,P<0.05). Five patients in the enteral nutrition group and 8 patients in the parenteral nutrition group developed abdominal distention and diarrhea, which were alleviated by adjusting doses or infusion speed. ConclusionsEarly enteral nutrition after laparoscopic hepatectomy for HCC is beneifcial to the postoperative recovery of gastrointestinal function and may effectively reduce the ifnancial burden of patients. Moreover, its overall curative effect is better than that of parenteral nutrition.

Objective To investigate the value of laparoscopic operation in the diagnosis and treatment of closed abdominal injury.Methods Forty-seven cases of closed abdominal trauma were diagnosed and treated under laparoscope from December 2003 to July 2006.Under general anaesthesia or epidural anesthesia,an incision about 1 cm was made below the umbilicus.Then artificial pneumoperitoneum was established through an open tunnel or the veress needle(according to patient's condition).The camera was inserted through a trocar to clarify the diagnosis.If a confirmative diagnosis was not obtained,one or two additional trocars were inserted for further exploration. When the diagnosis was identified,another two or three trocars were inserted according to the location of lesions and corresponding treatment was performed based on pathogenetic condition.Results All the 47 cases were confirmatively diagnosed under laparoscope,including 15 cases of hepatorrhexis,13 cases of splenic rupture,9 cases of small intestinal rupture,3 cases of mesenteric injury,2 cases of pancreatic injury,2 cases of retroperitoneal hematoma,and 3 cases of intraabdominal multiple organ injury.Laparoscopic treatment was completed in 28 cases,a conversion to open surgery was needed in 17 cases,and conservative treatment was given in 2 cases of retroperitoneal hematoma.No surgical related death or complications happened.Conclusions Laparoscopy can be used in closed abdominal trauma to achieve a high diagnostic accuracy and to give a timely,effective,and proper treatment.