Nrf2 knockout attenuates the astragaloside IV therapeutic effect on kidney fibrosis from liver cancer by regulating pSmad3C/3L pathways.

Fibrotic kidney injury from hepatocarcinogenesis seriously impacts treatment effect. Astragaloside IV (AS-IV), an extract of Astragalus membranaceus, has several pharmacological activities, which are useful in the treatment of edema and fibrosis. Nrf2/HO-1 is a key antioxidant stress pathway and help treatment of kidney injury. Smad3 phosphorylation is implicated in hepatocarcinogenesis. Our previous study clarified that Smad3 is differentially regulated by different phosphorylated forms of Smad3 on hepatocarcinogenesis. Therefore, we investigated the contribution of AS-IV on the therapy of kidney fibrosis from hepatocarcinogenesis. And the focus was on whether the phosphorylation of Smad3 and the regulation of Nrf2/HO-1 pathway were involved during AS-IV therapy and whether there is an effect of Nrf2 knockout on the phosphorylation of Smad3. We performed TGF-ß1 stimulation on HK-2 cells and intervened with AS-IV. Furtherly, we investigated renal injury of AS-IV on Nrf2 knockout mice during hepatocarcinogenesis and its mechanism of action. On the one hand, in vitro results showed that AS-IV reduced the ROS and α-SMA expression of HK-2 by promoting the expression pSmad3C/p21 of and Nrf2/HO-1 and suppressed the expression of pSmad3L/PAI-1. On the other hand, the in vivo results of histopathological features, serological biomarkers, and oxidative damage indicators showed that Nrf2 knockout aggravated renal injury. Besides, Nrf2 deletion decreased the nephroprotective effect of AS-IV by suppressing the pSmad3C/p21 pathway and promoting the pSmad3L/PAI-1 pathway. The experimental results were as we suspected. And we identify for the first time that Nrf2 deficiency increases renal fibrosis from hepatocarcinogenesis and attenuates the therapeutic effects of AS-IV via regulating pSmad3C/3L signal pathway.

Research status and prospect on the mechanisms of acupuncture and moxibustion treatment for constipation of Parkinson's disease. / é’ˆç¸æ²»ç–—å¸•é‡‘æ£®ç— ä¾¿ç§˜çš„æœºåˆ¶ç ”ç©¶çŽ°çŠ¶åŠå±•æœ›.

Constipation may accelerate the progression of Parkinson's disease (PD). The quality of life in PD patients can be significantly improved when constipation is treated, hence the disease progression may be delayed. At present, the mechanism research is still at the initial stage for acupuncture in treatment of PD, focusing on neurohumoral factors, intestinal flora, bacterial fermentation products and intestinal inflammation； and there are the problems such as single intervention, thinking limitation and insufficient cooperation among disciplines. This paper systematically reviews the mechanism research progress of acupuncture for the treatment of constipation in PD so as to provide the references for the subsequent studies.

Hyperoside mediates protection from diabetes kidney disease by regulating ROS-ERK signaling pathway and pyroptosis.

Renal tubular injury is a key factor in the progression of diabetic kidney disease to end-stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen-activated protein kinase signaling pathway, thereby alleviating proteinuria-induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment.

A Novel Paradigm Defines Functional Molecule Clusters for an Anti-Alzheimer's Disease Recipe from Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) prescriptions are organically composed of compatible herbs according to the TCM theory. The complex ingredients of TCM could act on multiple targets through various pathways simultaneously to exert pharmacological effects, making TCM an unrivaled gem in the medical world. However, due to a lack of comprehensive and standard study methods, the research of TCM products has been quite limited. A novel paradigm that could aid in the discovery of the material basis and fully clarify the mechanism of TCM prescriptions is urgently needed. In this study, a similarity analysis based on molecular fingerprints was adopted to explore the representative molecules of the Tiaoxin recipe, a Chinese patent formula approved by the National Medical Products Administration (NMPA) for the treatment of mild-to-moderate Alzheimer's disease (AD), and 38 out of 1047 chemicals were finally screened out. Next, we tried to define a new concept of a "functional molecule cluster" for chemicals with similar pharmacological effects to elucidate how the chemical mixture from TCMs produce their therapeutic effects. Four anti-AD functional molecule clusters from the Tiaoxin recipe were identified: an anti-inflammatory cluster, an anti-ROS cluster, an anti-AChE activity cluster, and an anti-A[Formula: see text] aggregation cluster. Furthermore, the chemicals from the anti-inflammatory cluster and anti-ROS cluster were proved to display their multi-target and multi-pathway roles partially or mainly through molecules of the TLR4-MYD88-NF-[Formula: see text]B and Keap1-Nrf2-ARE pathways. The functional molecule clusters may be vital to the explanation of the efficacy of the Tiaoxin recipe, which could give us a more profound understanding of TCM prescriptions. Our paradigm may open a novel path for TCM research.

[Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder].

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation.

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.

Effects of Kinesio Taping for Chronic Nonspecific Low Back Pain: A Systematic Review and Meta-analysis.

Context: Chronic nonspecific low back pain (CNLBP) is a common musculoskeletal disorder that seriously affects patients' quality of life (QoL). Clinicians have used Kinesio Taping (KT) in the treatment of CNLBP patients, but evidence is still lacking on the benefits of KT for CNLBP. Objective: The study aimed to perform a systematic review and meta-analysis of the currently published randomized controlled trails (RCTs) to determine KT's efficacy for CNLBP patients. Design: The research team performed a literature search using five major electronic databases-PubMed, Embase, Web of science, Cochrane Library, MEDLINE and OpenGrey-and included studies form inception to January 2018. The search used the keywords "kinesio tap*", "kinesio*", and "chronic low back pain (CLBP)" or "CNLBP". Setting: The study took place in the 942 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Outcome Measures: The research team performed the meta-analysis using RevMan 5.3 software. The team selected studies that used pain intensity and disability as the primary outcome measures, and if the study used other outcomes, they had to be the secondary outcomes. Results: The systematic review included nine RCTs in the meta-analysis. KT can significantly reduce pain intensity between baseline and immediately postintervention (SMD = -0.47, 95% CI -0.93 to -0.02, P = .04) and between baseline and the short-term follow-up period (SMD = -0.67, 95% CI -0.44 to -0.20, P = .03). However, no significant differences existed between KT's ability to relieve other symptoms of CNLBP-disability, trunk flexion range of motion (ROM), change in status, fear of movement, isometric endurance of the trunk muscles, or extension-when compared to either sham taping or KT as an adjunct to physical therapy. Conclusions: KT can have immediate and short-term positive effects on reducing pain intensity, but existing evidence doesn't support KT's superiority to other interventions in improving functions for individuals with CNLBP.

Noninvasive Transcutaneous Auricular Vagal Nerve Stimulation Improves Gastric Slow Waves Impaired by Cold Stress in Healthy Subjects.

BACKGROUND/AIMS: Stress is known to inhibit gastric motility. The aim of this study was to investigate the effects and autonomic mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) on cold stress (CS)-induced impairment in gastric motility that are relevant to the brain-gut interactions in healthy volunteers. MATERIALS AND METHODS: Healthy volunteers (eight women; age 28.2 ± 1.8 years) were studied in four randomized sessions (control, CS, CS + taVNS, and CS + sham-electrical stimulation [sham-ES]). Each session was composed of 30 minutes in the fasting state and 30 minutes after a standard test meal. CS was induced during minutes 10 to 30 after the meal, whereas taVNS or sham-ES was performed during minutes 0 to 30 after the meal. The electrogastrogram and electrocardiogram were recorded for assessing gastric slow waves and autonomic functions, respectively. RESULTS: First, CS decreased the percentage of normal gastric slow waves (59.7% ± 9.8% vs 85.4% ± 4.5%, p < 0.001 vs control); this impairment was dramatically improved by taVNS (75.5% ± 6.3% vs 58.4% ± 12.5%, p < 0.001 vs sham-ES). Second, CS increased the symptom score (22.0 ± 12.1 vs 39.3 ± 11.5, p = 0.001 vs control); taVNS, but not sham-ES, reduced the symptom score (26.0 ± 12.2 vs 38.3 ± 21.6, p = 0.026 vs sham-ES). Third, CS decreased vagal activity assessed from the spectral analysis of heart rate variability (0.21 ± 0.10 vs 0.26 ± 0.11, p < 0.05 vs control) and increased the sympathovagal ratio (4.89 ± 1.94 vs 3.74 ± 1.32, p = 0.048 vs control); taVNS normalized CS-induced suppression in vagal activity (0.27 ± 0.13 vs 0.22 ± 0.10, p = 0.049 vs sham-ES; p > 0.05 vs control) and CS-induced increase in the sympathovagal ratio (3.28 ± 1.61 vs 4.28 ± 2.10, p = 0.042 vs sham-ES; p > 0.05 vs control). CONCLUSION: The noninvasive taVNS improves the CS-induced impairment in gastric pace-making activity, possibly by reversing the detrimental effect of CS on autonomic functions. taVNS may have a therapeutic potential for stress-induced gastric dysmotility.

[Scoping review of clinical evidence of Chinese patent medicines for digestive system diseases in children].

This study analyzed and reported the basic information and clinical evidence of Chinese patent medicines for digestive system diseases in children in a scoping review manner. Based on the drug instructions, the basic information of Chinese patent medicines for digestive system diseases in children was obtained by searching the three lists of national medicines. At the same time, the relevant clinical literatures from the first day of establishment to March 7, 2022 were obtained from Chinese and English databases. According to the screening criteria, 39 Chinese patent medicines were included, involving 8 dosage forms. Eight Chinese medicines including Crataegi Fructus, Poria, Citri Reticulatae Pericarpium, Hordei Fructus Germinatus, Arecae Semen, Massa Medicata Fermentata, Dioscoreae Rhizoma, and Atractylodis Macrocephalae Rhizoma were frequently used, and the main effects were invigorating spleen, checking diarrhea, promoting digestion, clearing heat, and harmonizing stomach. The indications for Chinese patent medicines were mainly diarrhea, anorexia, food accumulation, dyspepsia, and rotavirus enteritis in children. Among all drug instructions, only 4 mentioned adverse reactions and 6 mentioned contraindications. Ninety-two clinical studies were included ultimately, including 84 randomized controlled studies, 2 systematic reviews/Meta-analysis, 1 retrospective study, and 5 case series. The literatures only covered 21 kinds of Chinese patent medicines, with the most studies related to Xingpi Yanger Granules, accounting for 32.6% of the total literature volume. The sample size in the literatures was mainly focused on 51-200 cases, and 51-100 cases were selected by the most literatures, accounting for 34.45%. The interventions of the experimental group were mainly Chinese patent medicines or Chinese patent medicines combined with western medicines. The literatures with treatment course of 0-7 d accounted for the largest proportion(51.10%). The effective rate and symptom improvement time were used as the indexes to evaluate the results. The main adverse reactions were vomiting, constipation, nausea, rash, cold, diarrhea, redness of the skin around the umbilicus, or red itchy skin. The analysis of this study found that Chinese patent medicines have good curative effect and research prospects in the treatment of digestive system diseases in children. However, most clinical evidence has problems, such as limited indexes to evaluate the results, lack of traditional Chinese medicine characteristics, uneven quantity and low quality of Chinese patent medicine literatures, and insufficient specification of instructions. In the future, high-quality clinical studies on this field should be actively carried out, and economic studies and clinical comprehensive evaluation of Chinese patent medicines should be strengthened to explore the characteristics and advantages of its treatment, so as to provide decision-making basis for finding the accurate clinical positioning and promoting the rational clinical application of Chinese patent medicines for treating digestive system diseases in children.

[Four Chinese patent medicines for regulating stomach for functional dyspepsia: a rapid health technology assessment].

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.

[Secondary metabolites of endophyte Hypoxylon sp. HD-2014 from Uncaria rhynchophylla].

This study aims to investigate the compounds in the product of rice fermented with endophyte Hypoxylon sp.HD-2014 from Uncaria rhynchophylla.To be specific, normal-phase, MCI, Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was used to yield 12 compounds.Through spectral data analysis and comparison with previous reports, they were identified as methyl(E)-5-hydroxymethyl-6,7-dihydroxy-4,5-epoxy-octanoate-2-ene(1),(2E,6E)-nona-2,6,8-triene-4,5-diol(2), 8-O-(R)-methoxynodulisporin A(3), 3-nitropropionic acid(4), 3-nitropropionic acid methyl ester(5), 3,4-dihydroxy-phenylethanol(6), 2,4-dichlorobenzoic acid(7), cis-4-hydroxyscytalone(8), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(9), isosclerone(10), 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxyl-methyl)-2-methy(11), and 5-methylmellein(12), respectively.Compounds 1 and 2 were identified for the first time.In vitro cytotoxicity test indicated that compounds 1-12 had no significant inhibitory effect on A549 and HepG2 cells.Antimicrobial susceptibility testing revealed that compound 3 showed synergistic effect with the positive control chloramphenicol.

[Scoping review of domestic and overseas hospital-based health technology assessment].

This paper systematically sorted out the related research on hospital-based health technology assessment(HB-HTA) and clarified the research status of this field to provide a basis for the future research direction and focus of HTA in traditional Chinese medicine(TCM) hospitals. Based on the scoping review, relevant research papers were retrieved from Chinese databases(including CNKI, Wanfang, VIP, and SinoMed) and PubMed and analyzed. Among the included 99 papers, the earliest one was published in 2005 in China, and the number of papers has been increasing since 2016. In terms of journals, the included papers were published in 39 journals, including 24 core ones and 2 SCI ones. In terms of the number of publications, the Chinese Journal of Evidence-Based Medicine accounted for the majority(n=6). Among the 175 authors involved, three of them published 15 papers, respectively, accounting for 20.83% and ranking the top, and they came from Renmin University of China and the National Health Commission of China. There were 38 first units dominated by hospitals. Hebei General Hospital published the most papers(n=10), followed by Renmin University of China(n=9) and the National Health Commission of China(n=7). In terms of research type, the research papers were dominated by evaluation and practice ones(n=29), followed by reviews(n=20). In terms of research topic, the research was mainly carried out from devices(n=26) and macro-perspective scope(n=24). Half of the research in China was funded. For 27 research papers published abroad, the number of publications in the past five years was small, with 16 countries involved. Developed countries paid more attention to this field than developing countries. Especially in Europe and the US, the publishing institutions were mainly universities, and the types of research were mainly interviews and evaluation or practice. In recent years, the attention of HB-HTA in China has been increasing year by year, and the development of related projects has provided a scientific decision-making basis for the admission and management of new technologies in hospitals in China. However, there are few researchers and institutions in this field, and the research scope is small. In the future, more investment is needed to encourage more hospitals, especially TCM hospitals, to carry out HB-HTA, explore the HB-HTA system suitable for Chinese conditions, and improve the scientific decision-making of hospitals.

[Scoping review of rapid health technology assessment].

This study aims to summarize the research on rapid health technology assessment(RHTA) based on scoping review, which is expected to serve as a reference for future research on RHTA. First, articles on RHTA were retrieved from both Chinese and English databases. After data screening and extraction by two personnel independently, descriptive analysis was conducted on the results, and evidence distribution was analyzed based on tables, bar charts, line charts, radar charts, and pie charts. Finally, a total of 82 eligible articles were included and the characteristics were as follows.(1) Articles on RHTA were mainly published from 2011 to 2022. The number of articles showed an obvious increase from 2014 and surged in 2019.(2) Among the journals with the above RHTA papers published, Chinese Journal of New Drugs(21.5%), Evaluation and Analysis of Drug-Use in Hospitals of China(16.9%), and Chinese Pharmacy(15.4%) topped the Chinese journals in the number of the papers, while International Journal of Technology Assessment in Health Care(23.5%), Reviews in Medical Virology(11.8%), and Value in Health(11.8%) came out on top in the English journals.(3)The RHTA of drugs(especially western medicine)(68.7%) dominated the eligible articles, followed by the RHTA of therapy technology(13.1%), detection technology(5.1%), and diagnosis technology(1.0%). There was a significant gap in the number of studies among different health technology categories and an imbalance in the types of health technologies involved in the overall RHTA studies.(4) RHTA of tumors has been the research focus in recent years. In summary, RHTA plays a positive role in rapid health decision-making, but there is a lack of primary data sources at present. Compared with the systematic review, Meta-analysis, and pharmacoeconomic studies, a few reports on health technology assessment(HTA) were included. In the future, research on the evaluation of the safety, efficacy, cost effectiveness and social applicability of health technologies should be further strengthened.

[Rapid health technology assessment of four oral Chinese patent medicines for constipation].

This study evaluated the safety, efficacy, and cost effectiveness of Biantong Capsules(Tablets), Maren Runchang Pills, Qirong Runchang Oral Liquid, and Qihuang Tongmi Soft Capsules in the treatment of constipation by the rapid health technology assessment(RHTA) to provide evidence for clinical decision and references for rapid evaluation of Chinese patent medicine(CPM). CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science, and Cochrane Library were searched for research articles from database inception to February 2022. Two reviewers conducted literature screening, data extraction, and quality evaluation according to the predetermined standards. Descriptive analysis of the results combined with visual charts was performed. Sixty research articles were included, involving 44 randomized controlled trials(RCTs), 7 clinical controlled trials(CCTs), 4 systematic reviews/Meta-analyses, and 5 economic analysis studies. As revealed by the results, Biantong Capsules(Tablets) could be used for postoperative and senile constipation, in which some studies reported Biantong Capsules(Tablets) were superior to Maren Runchang Pills and Qirong Runchang Oral Liquid. Maren Runchang Pills were mainly used for senile constipation, and the efficacy was similar to that of conventional wes-tern medicine, but the cost was low and the compliance of patients was good. Qirong Runchang Oral Liquid was indicated for disease-derived or drug-induced constipation, chronic constipation, and senile constipation with fewer adverse reactions. Qihuang Tongmi Soft Capsules had good efficacy and safety in the treatment of functional constipation. Overall, compared with western medicine glycerine enema and lactulose, the number of clinical studies of the four CMPs was small, but they targeted constipation patients with different subtypes. In conclusion, the four CMPs have their advantages and characteristics in the treatment of constipation, but they are restric-ted by sparse existing evidence, low quality of evidence, and insufficient economic research. In the future, more high-quality and long-term follow-up studies should be carried out to obtain reliable evidence. Meanwhile, it is called for strengthening the economic evaluation of CMPs to provide evidence for decision-making.

[Multi-criteria decision analysis in clinical comprehensive evaluation of Chinese patent medicine].

Multi-criteria decision analysis(MCDA), a comprehensive analysis method that can help decision-makers consider multiple criteria systematically, has been used for clinical comprehensive evaluation of drugs, such as chemicals and Chinese patent medicines. The present study summarized the theoretical basis of MCDA and its application in the clinical comprehensive evaluation of drugs and put forward suggestions. MCDA includes problem identification, structuring problem, model building, and using the model to inform and challenge thinking to develop an action plan. The modeling methods include value measurement models, outranking models, and reference-level models. The value measurement model is the most commonly used method in healthcare. The implementation steps of MCDA consist of defining the decision problem, selecting and structuring criteria, measuring performance, scoring alternatives, weighting criteria, calculating aggregate scores, dealing with uncertainty, and reporting and examination of findings. It is urgent to carry out the clinical comprehensive evaluation of Chinese patent medicine, the important part of traditional Chinese medicine(TCM), to promote its scientization, homogenization, and standardization. It is of great significance to carry out the clinical comprehensive evaluation of Chinese patent medicine with MCDA, which should be demand-oriented, coordinated by many parties, and learn from international experience and successful practice to establish the corresponding technical guidelines, specifications, and evaluation tools, so as to provide technical support for Chinese patent medicine supply and policy formulation.

[Enlightenment of WHO guideline on institutionalizing health technology assessment mechanism for traditional Chinese medicine].

To promote the institutionalization of the health technology assessment(HTA) mechanism in various countries, World Health Organization(WHO) has published the Institutionalizing Health Technology Assessment Mechanisms: a How to Guide to introduce five steps of institutionalizing the HTA mechanism systematically, specifically, "establishing a mandate; establishing the legal framework; reviewing or establishing the legal framework; establishing institutional and governance arrangements; processes and evidence required for assessment and appraisal; and monitoring and evaluation". Traditional Chinese medicine(TCM) HTA can provide scientific information and decision-making evidence for decision-makers at all levels to select TCM health technology reasonably, and promote the high-quality development of the TCM healthcare system. However, TCM HTA is in its infancy, and it is imperative to carry out relevant work under the guidance of global standard documents to ensure standardization, transparency, and fairness. In light of the WHO guidance, this research group put forward the necessity and logical framework for the institutionalizing HTA mechanism of TCM, which is helpful to establish the institutionalizing HTA mechanism in line with national conditions and suitable for TCM, provide scientific guidance for the research of TCM HTA, and contribute to TCM healthcare decision-making.

Use of levosimendan combined with Shenfu injection to treat acute heart failure patients with hypotension: a prospective randomized controlled single-blind study.

BACKGROUND: Levosimendan can improve clinical symptoms and the cardiorenal rescue success rate, and stabilize hemodynamic parameters in individuals suffering from acute decompensated heart failure. In addition, Shenfu injection (SFI) has been shown to protect the ischemic heart and enhance myocardial contractility. METHODS: For this randomized control single-blind study, 101 patients with acute decompensated heart failure (ADHF) were enrolled and randomly assigned to control levosimendan (n = 51) and levosimendan + SFI injection (n = 50) groups. Attending physicians were not blinded for which arm the patients were allocated. Blood pressure, heart rate, the electrocardiogram, respiratory rate, fluid intake and urine output were all recorded 2 h and 24 h after drug infusions had commenced, and the cardiac index (CI) was monitored by ultrasonic cardiac output monitors. RESULTS: Median blood pressure was markedly increased in the levosimendan + SFI group after 2 h and 24 h from the initiation of infusions compared to levosimendan administration alone. Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001). Alterations in BNP concentrations were not different in the combination and control groups. No differences were found between the 2 groups in heart rate or severe hypotension, but blood pressure (systolic blood pressure, diastolic blood pressure) and hemodynamic parameters including CI, cardiac output and stroke volume index responded better in the levosimendan + SFI group compared to the monotherapy levosimendan group. CONCLUSIONS: Levosimendan + SFI was superior to treat ADHF patients compared to levosimendan monotherapy and produced significant improvements in hemodynamic parameters especially for ADHF patients with hypotension. Trail registration The study was prospectively registered at Chinese Clinical Trial Registry with registration number [ChiCTR2000039385] (10/25/2020).

Ganoderma modulates allergic asthma pathologic features via anti-inflammatory effects.

Ganoderma, a fungal genus, is a traditional medicine with immuno-modulating effects. Asthma is an inflammatory disease of airways, and the main trigger of asthma is allergic inflammation. In this study, the effects of Ganoderma (an anti-inflammatory agent) given via oral administration (G/O) or intraperitoneal injection (G/IP) on asthma was evaluated. Forty BALB/c mice were divided into four groups, including the control, OVA-challenge, OVA-challenge + G/O, and OVA-challenge + G/IP. To determine AHR, the MCh challenge test was done. The levels of IL-1ß, -4, -5, -6, -8, -10, -12, -13, -17, -25, -33, -38, Cys-LT, LTB4, and hydroxyproline were measured. Finally, lung histopathology was evaluated to determine eosinophilic inflammation, goblet cell hyperplasia, and mucus hyper-secretion. Treatment with G/O and G/IP could significantly reduce the levels of IL-1ß, -5, -6, -8, -17, -25, -33, and -38; the levels of IL-4 and IL-13 had no significant changes, but the levels of IL-10 and IL-12 were enhanced. The mice treated with G/O and G/IP showed decreased levels of Cys-LT, LTB4, peribronchial and perivascular inflammation, but no significant changes were observed in AHR, hydroxyproline level, goblet cell hyperplasia, and mucus hyper-secretion. Ganoderma can be applied as an immunomodulatory and anti-inflammatory agent for managing asthma.

Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice.

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8+ T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8+ T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8+ T cell responses in COVID-19 patients.