OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Menopausal syndromes are mostly based on kidney deficiency， which could be expalined that kidney governing essence storage and controlling innateness， so when the kidney water was deficient and the liver fail to nourish， then led to liver depression and transform into fire； deficiency of the kidney， loss of warmth of the spleen， and inability to transport and transform the water and dampness will easily lead to phlegm and fire； the decline of the kidney yin and loss of water and fire will easily cause the exuberance of heart fire. Therefore， clinical symptoms of hot flashes， insomnia， and palpitations are common due to phlegm， depressions， and fire. Based on this， at the beginning of the treatment， we should treat the symptoms firstly by resolving phlegm， relieving depression and clearing fire， and commonly use Huanglian Wendan Decoction （黄连温胆汤）， Yigan Powder （抑肝散）， Chaihu plus Longgu Muli Decoction （柴胡加龙骨牡蛎汤）， and Qingxin Zishen Decoction （清心滋肾饮）， etc. After improving the symptoms of hot flashes and sweating， irritability， dreaming and frightening， then we should give the prescriptions to tonify kidney yang and nourish kidney yin， in order to eliminate the pathogens and reinforce healthy qi， and to treat both the manifestations and the root cause， so that the symptoms of the patients can be better alleviated.

Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

OBJECTIVE: To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients. METHODS: Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients. RESULTS: Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months). CONCLUSION The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.
Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics* ; MicroRNAs/genetics* ; Neoplasm Recurrence, Local ; Prognosis

Organ transplantation is an effective treatment for end-stage organ failure. However, organ shortage has always been a common problem faced by countries around the world. The recognition and active participation of intensive care unit (ICU) medical staff in organ donation contributes to promoting the development of organ donation, thereby alleviating the shortage of donor organ. In this article, the key strategies of ICU donor management to promote organ donation and the key strategies of ICU medical staff management to promote organ donation were summarized, aiming to provide reference for organ donation practitioners (especially ICU medical staff) and jointly facilitate the professional development of organ donation.

The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine.This review summarizes and analyses the research progress on metabolism effects of gut microbiota on Chinese medicines components, the regulating effect of effective ingredients from Chinese medicine on intestinal probiotics, the application status of probiotics in traditional Chinese medicines, and the main problems and prospects in the research and development of Chinese medicines products with probiotic, aiming to provide theoretical guidance and practical value for the fermentation engineering of Chinese herbal medicine.
Drugs, Chinese Herbal ; metabolism ; Humans ; Medicine, Chinese Traditional ; Probiotics

Objective To evaluate the relationship between anterior chamber angle and intraocular pressure (IOP) after laser peripheral iridotomy (LPI) treatment.Methods A retrospective cases control study was adopted.Fifty-eight patients (58 eyes) who were diagnosed as primary angle closure (PAC) were included in this study.Ultrasound biomicroscopy (UBM) parameters in angle opening distance (AOD),trabecular iris area (TISA) and angle recess area (ARA) examination were performed before LPI.The changes of intraocular pressure (IOP) were compared between different time-points (before and 1 hour,2 hours,8 hours,24 hours,2 weeks,6 months and 12 months after LPI).The patients were divided into IOP≤21 mmHg group (41 eyes) and IOP＞21 mmHg group (17 eyes) after LPI.Relationship between anterior chamber angle and IOP after LPI treatment was explored.This study was approved by Ethic Committee of the Henan Eye Institute and informed consent was obtained from each patient.Results The IOPs were increased in 1 hour,2 hours after LPI and lowered in 2 weeks,6 months,12 months after LPI compared with IOP before LPI,with significant differences between them (all at P＜0.01).Twelve patients suffered transient elevated IOP and recovered by self-healing or treatment.IOP of 4 patients were elevated after 6 months to 1 year follow-up.The IOPs in 2 weeks,6 months and 12 months after LPI were lowered compared with IOP before LPI,with significant differences between them (all at P＜0.01).The UBM parameters were significantly increased in 2 weeks,6 months,12 months after LPI in comparison with IOP before IPL (all at P＜0.01).IOP and UBM parameters values were significantly different between IOP＞21 mmHg group and ≤21 mmHg group after LPI.Regression analysis indicated that ARA750 (OR =0.75,P＜0.05) was correlated to the IOP after LPI rather than IOP before operation,AOD and TISA (P＞0.05).Conclusions ARA750 value is correlated with the IOP variations after LPI.UBM structured observation can improve the surgical successful rates and safty and prevent complications.

Objective:To study the biological safety and biocompatibility of the mixture of Paris polyphylla-chitosan.Methods:According to the GB/T 16886.12-2005 standard,YY/T 0279-1995 standard and GBT16886.5-2003 standard,samples were prepared and tested by oral mucous membrane irritation test,cytotoxicity test and flow cytometry.Results:No local response to the mixture of Paris polyphylla-chitosan was found,and the visual observation and pathological findings of oral mucosa were normal and similar to that of the control group.Therefore,the mixture of Paris polyphylla-chitosan had no irritation response to oral mucosa.The mixture of Paris polyphylla-chitosan showed no cytotoxicity to L929 cells,and did not affect the cycle distribution and apoptosis of L929 cells.Conclusion:The mixture of Paris polyphylla-chitosan has good bio-safety and biocompatibility.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.