[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

[Evaluation for druggability of traditional Chinese medicine preparations in medical institutions based on human use experience].

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis­related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC. METHODS: Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets. RESULTS: Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e-14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e-02, and Asian: P = 6.342e-08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets. CONCLUSION: The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.

Efficacy and safety of bifid triple viable plus aminosalicylic acid for the treatment of ulcerative colitis: A systematic review and meta-analysis.

OBJECTIVE: Ulcerative colitis (UC), one of the most stubborn diseases, is mainly treated by aminosalicylic acid (ASA). However, the side effects of ASA include vomiting, nausea, rash, diarrhea, headache, etc, which seriously affect life-quality of UC patients. Probiotics such as bifid triple viable (BTV) could reduce drug-induced adverse reactions and has a good clinical effect on UC. Therefore, we aimed to evaluate the clinical efficacy and safety of BTV plus ASA in treating UC. METHODS: PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang databases were searched from the inception dates to October 12, 2018. Randomized controlled trials (RCTs) were included by comparing BTV plus ASA programs with ASA alone in patients with UC. Methodological quality was assessed by 2 independent researchers according to the inclusion criteria and exclusion criteria. Meta-analysis was performed by using the Review Manager 5.3 Software. Risk ratios (RRs), 95% confidence interval (CI), and standardized mean difference were calculated. RESULTS: Sixty RCTs involving 4954 participants were selected for final review. Compared with ASA, BTV plus ASA significantly improved the clinical effect rate [RR = 1.23, 95% CI (1.20, 1.26), P < .00001]; reduced the relapse rate [RR = 0.34, 95% CI (0.18, 0.62), P = .0005]; and adverse effect rate [RR = 0.66, 95% CI (0.53, 0.82), P = .0002]. Compared with the controls, levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, C-reactive protein (CRP), hypersensitive CRP, erythrocyte sedimentation rate, and malondialdehyde were reduced; levels of IL-10, CD3+, CD4+, and superoxide dismutase were increased in BTV plus ASA group. CONCLUSIONS: BTV plus ASA has positive therapeutic effects on UC, and it might be a safe way to treat UC. However, comprehensive clinical trials are needed to obtain high level of clinical evidence.

Efficacy and safety of Kangfuxin liquid combined with aminosalicylic acid for the treatment of ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC). METHODS: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool. RESULTS: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RR = 1.19, 95% CI: (1.16, 1.23), P < .00001], reduced the relapse rate [RR = 0.26, 95% CI: (0.18, 0.38), P < .00001], reduced the inflammation factor levels of TNF-a, IL-1, IL-6, IL-8, and C-reactive protein, reduced the coagulation index of fibrinogen, increased the coagulation index of prothrombin time, and mean platelet volume, and reduced the clinical symptoms of abdominal pain, diarrhoea, pus and bloody stool, and tenesmus. However, KFXL combined with ASA did not increase the adverse event incidence [RR = 0.74, 95% CI (0.42, 1.32), P = .31], and no severe adverse events were reported. CONCLUSION: KFXL combined with ASA has good therapeutic effect for UC and might be a safe approach in managing UC. More high-quality, multicenter randomized, double-blind trials with a large sample size are required to generate a high level of clinical evidence.

Hepatocyte growth factor is a prognostic marker in patients with colorectal cancer: a meta-analysis.

Hepatocyte growth factor (HGF) is a crucial factor associated with development, progression and metastasis of colorectal cancer (CRC). However, its prognostic value remains unclear. Thus studies referring to the correlation between HGF and CRC patients' prognosis were included to explore the role of HGF in CRC. At last nine articles were included. The results showed that the over-expression of HGF was associated with a poor prognosis, presented through overall survival (OS, Hazard ratio (HR) = 2.50, 95% confidence interval (CI): 2.12-2.96) and disease-free survival (DFS, HR = 1.99, 95% CI: 1.59-2.50). Subgroup analysis indicated that no significant difference was found between the Asian countries (OS: HR = 2.37; DFS: HR = 2.02) and the non-Asian countries (OS: HR = 3.15; DFS: HR = 1.87), between the studies that used univariate analyses (OS: HR = 2.51; DFS: HR = 2.07) and those that used multivariate analyses (OS: HR = 2.65; DFS: HR = 1.78), and between metastatic CRC (OS: HR = 2.26; DFS: HR = 2.06) and stage I-IV CRC (OS: HR = 3.08; DFS: HR = 0.70). Our meta-analysis has shown that the over-expression of HGF is valuable in CRC prognosis evaluation. This conclusion should be further confirmed by large-sample cohort studies.

Translation and validation of the Chinese version of the Quality OF Life Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N).

BACKGROUND: To translate and validate the Chinese version of the Quality Of Life Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N), a disease-specific scale to measure quality of life (QOL) for patients with head and neck cancer (HNC) who received radiotherapy. METHODS: The QOL-RTI/H&N was translated and validated according to the standard process: a translation and back-translation procedure, pilot testing and a validation study. HNC patients were enrolled from the Cancer Center of Sun Yat-sen University and assessed using the QOL-RTI/H&N, QLQ-C30 and QLQ-H&N35. Reliability (internal consistency reliability, split-half reliability and test-retest reliability), validity (content validity, construct validity, criterion validity and discriminant validity), and responsiveness analysis were performed to evaluate the psychometric characteristics of the QOL-RTI/H&N. RESULTS: A total of 238 patients (99.2%) completed the questionnaire. Item RTI23 had 16.0% missing data. Other items had low percentages of missing data (0.4% or 0.8%) or no missing data. The average time to finish the scale was 9.8 minutes. Cronbach's alpha of the domains ranged from 0.41 to 0.77. The split-half reliability coefficients ranged from 0.43 to 0.77. All of the intra-class correlation coefficients were equal to or greater than 0.8. All of the item-own domain correlation coefficients were greater than those of the item-other domain. Confirmatory factor analysis showed that Comparative Fit Index, Normed Fit Index and Non-Normed Fit Index were equal to 1.00. Root Mean Square Error of Approximation was 0.01, with 90% CI (0.00, 0.10). The domain scores of the QOL-RTI/H&N were significantly correlated with those of the QLQ-C30 or QLQ-H&N3. All domain scores of patients in different radiotherapy stages were statistically significant (P < 0.05), apart from the speech domain. CONCLUSIONS: The Chinese version of the QOL-RTI/H&N is a valid, reliable and responsive scale to measure QOL in HNC patients and can be used to assess the effects of radiotherapy treatment on these patients.

[Effect of changji'an capsule on mRNA expressions of NPY and ACTH contents in brain-gut axis of IBS-D model rats].

OBJECTIVE: To explore the effect of Changji'an Capsule (CA) on mRNA expressions of neuropeptide Y (NPY) in the hypothalamus and colon and serum levels of adreno-cortico-tropic hormone (ACTH) in rats of diarrhea predominant irritable bowel syndrome (IBS-D) model rats. METHODS: Totally 48 SD rats were randomly divided into six groups, i.e., the normal control group, the model group, the Pinaverium Bromide group (PB, 0.018 g/kg), the high dose CA group (2.812 g/kg), the medium dose CA group (1.406 g/kg), and the low dose CA group (0.703 g/kg), 8 in each group. The IBS-D rat model was established by using separation of breast milk + stimulation of acetic acid + constraint of four limbs. Normal saline was given to rats in the normal control group and the model group. All medication lasted for 14 successive days by gastrogavage. The serum content of ACTH was detected by enzyme linked immunosorbent assay (ELISA). The expressions of NPY mRNA in the colon and the hypothalamus were detected using real-time fluorescence quantitative PCR. RESULTS: Compared with the normal control group, the serum ACTH content significantly increased (P < 0.01), the NPY mRNA expression in the colon and the hypothalamus obviously decreased (P < 0.01) in the model control group. Compared with the model group, the serum ACTH obviously decreased in the high dose CA group, the medium dose CA group, and the PB group (P < 0.01, P < 0.05). The NPY mRNA expression in the colon and the hypothalamus were obviously up-regulated in the high dose CA group, the medium dose CA group, the low dose CA group, and the PB group (P < 0.05). CONCLUSIONS: CA could modulate the abnormity of brain-gut axis of IBS-D rats possibly by up-regulating NPY mRNA expressions in the hypothalamus and the colon and down-regulating the ACTH content in the hypothalamic-pituitary-adrenal axis.

[Study on preparation and determination of Liaojin plastics].

OBJECTIVE: To establish the optimum preparation and determination method of Liaojin plastics through screening different factors. METHODS: The Orthogonal Test was applied to optimize the best preparation technology, and the content of peoniflorin in Liaojin plastics was determined by HPLC. RESULTS: The best matrix proportion of plastics was PVA-124 : alcohol : acetone : distilled water = 1 : 4 : 2 : 10; The average recovery of plastics was 98.56%, RSD was 1.66% (n = 9), and the average content of six samples was 0.6817 mg/g, RSD was 1.44%. CONCLUSION: The good quality plastics can be produced through this process. HPLC determination method is simple, reliable and can be used in the quality control of Liaojin plastics.