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 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 study the complete genome characterization of Human Astrovirus (HAstV) in Shandong Province.Methods:Stool samples from acute flaccid paralysis (AFP) surveillance in Shandong Province from 2020 to 2022 were collected, and HAstV nucleic acid was examined by real-time quantitative PCR (qPCR). Next-generation sequencing (NGS) was conducted for the positive samples to obtain complete genome sequences and identify the genotype. Homology comparison and phylogenetic analysis were performed by using BioEdit and Mega software.Results:A total of 667 samples were examined by qPCR, of which 14 were HAstV-positive (2.1%), including HAstV-1 ( n=6), MLB1 ( n=6), MLB2 ( n=1), and VA2 ( n=1). The complete genome sequences were obtained from 11 samples. The six HAstV-1 sequences of this study had 98.2% to 99.9% nt similarities with each other and 87.6% to 98.6% with those from other regions. The four MLB1 sequences of this study had 99.1% to 99.9% nt similarities with each other and 92.2% to 99.4% with those from other regions. The VA2 sequence of this study had 96.0% to 96.3% nt similarities with those from other regions. Phylogenetic analysis based on ORF2 region showed that the local HAstV-1 sequences were most closely related to Japanese strains, and had distinct topology with phylogenies based on ORF1a and ORF1b regions. Conclusion:The complete genome sequences of 11 HAstV strains are obtained, and the VA2 complete genome is found.

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.

Objective To study the mechanism of Chaihu Guizhi Decoction(CGD)in the treatment of influenza and staphylococcus aureus co-infection.Methods The co-infection model of influenza and staphylococcus aureus was established and CGD was used to intervene.The chemical components of CGD were qualitatively analyzed by UPLC-Q-Exactive/MS technology.The potential action targets of chemical components in CGD and the related targets of influenza Staphylococcus aureus co-infection were mined by network pharmacology method.The"component target disease"network was constructed.Core targets were selected according to degree ranking.Core action pathways were enriched by KEGG analysis and GO annotation analysis.The core target was verified by RT-qPCR,and the interaction between the core component and the key target was verified by molecular docking.Results CGD could significantly improve the decrease of body weight and thymus index(P<0.05)caused by co-infection.The lung index(P<0.05),relative amount of MmRNA expression(P<0.05)and bacterial load(P<0.05)were decreased,and the survival rate was improved.51 chemical constituents were identified from CGD.Through network pharmacological analysis,107 related targets corresponding to CGD treatment of bacterial pneumonia secondary to influenza were excavated.TNF,AKT1,ALB,VEGFA,MAPK3,PTGS2,STAT3,EGFR and other targets with strong correlation,mainly involved Fc epsilon RI signal pathway,GnRH signal pathway,NF-κB signal path,etc.Molecular docking study showed that the main active component of CGD,including oroxyloside,baicalein and wogonin have strong affinity with TNF,PTGS2 and EGFR targets.Compared with co-infection model group,in CGD group TNF-α、EGFR and PTGS2 increased significantly(P<0.05).Conclusion The main active ingredient of CGD is oroxyloside,baicalein and wogonin.TNF-α,PTGS2,EGFR and other targets to played a role in the treatment of influenza staphylococcus aureus co-infection.

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.

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.

Objective:To investigate the clinical treatment of large segmental humeral defects with unilateral external fixation and bone transport.Methods:A retrospective study was conducted of the 9 patients who had been treated at Department of Orthopedics, Shenzhen People's Hospital for large segmental humeral defects from September 2017 to June 2019. They were 5 males and 4 females with an average age of 29 years (from 21 to 41 years). Their defects were caused by trauma in 2 cases, by chronic osteomyelitis in 6 cases and by bone tumor in one case. The length of bone defect ranged from 4.2 to 9.0 cm, with an average of 5.9 cm. A unilateral external fixator was placed in operation, and adjusted regularly 7 to 10 days after operation for bone transport and bone lengthening to restore the length of humerus gradually. The external fixation bracket was removed after 3 to 4 layers of cortex were observed on X-ray films. Recorded were length and rate of humeral lengthening, fracture healing time, time for carrying external fixator and complications; the Disabilities of the Arm, Shoulder and Hand (DASH) scores were compared between preoperation and 15 months postoperation.Results:All the patients were followed up for 15 to 36 months (mean, 19 months). The length of lengthening averaged 5.9 cm (from 4.2 to 9.0 cm) with an average lengthening rate of 26%, the healing index 31 d/cm, the bone healing time 8.3 months, and the time for carrying external fixator 10.8 months(from 8.0 to 13.5 months). Their average DASH scores improved significantly from 25.0 ± 2.4 preoperation to 12.0 ± 1.8 at 15 months postoperation ( P<0.05). Good correction of large humeral defects was achieved in all but one case who reported temporary radial nerve paralysis. There were no such complications as neurovascular injury. The shoulder and elbow functions were basically normal after operation. Conclusions:In the treatment of large segmental humeral defects, unilateral external fixation plus bone transport can quickly repair the defects and recover the upper limb function of the patients.