[Evaluation methods of clinical efficacy of traditional Chinese medicine].

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Effect of acupuncture in eczema: An overview of systematic reviews.

BACKGROUND: Eczema is a common chronic relapsing inflammatory skin disease, which is characterized by intense itching. Acupuncture can be effective for eczema, and it is thus regarded as a common complementary treatment. OBJECTIVE: The intention of this overview is to methodically appraise and synthesize evidence about systematic reviews/meta-analyses (SRs/MAs) on acupuncture in eczema. METHODS: We searched for SRs/MAs of acupuncture with eczema in eight databases. We evaluated the methodological quality by Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the reporting quality with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020 Checkist), and the evidence quality according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A total of 7 SRs/MAs were included. According to AMSTAR-2, all the SRs/MAs included were categorized as critically low-quality. According to the PRISMA 2020 checklist, none of the reviews completed all the 27 items, thus their compliance was relatively weak. On the base of GRADE system, 2 of the 12 outcomes were rated as moderate, and 5 outcomes were rated as low-quality, while the others were regarded as very low-quality. CONCLUSION: Compared with the control group, the included reviews of the acupuncture group were more effective and safer; however, the conclusion should be treated cautiously because the quality of evidence was not high enough to support it. In order to improve the quality, more rigorous, standardized, and comprehensive SRs/MAs need designing in the future.

Efficacy and safety of zhibitai in the treatment of hyperlipidemia: A systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of Zhibitai (ZBT) in the treatment of patients with hyperlipidemia (HLP). Methods: A search of 8 electronic databases was conducted to find randomized controlled trials (RCTs), to evaluate the efficacy and safety of ZBT for the treatment of HLP. The risk of bias in randomized controlled trials was assessed by using the Cochrane Collaboration Risk of Bias tool for randomized controlled trials 2.0 (RoB 2.0). The primary outcomes were the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The total effective rate served as the secondary outcome. The incidence of adverse events was considered the safety outcome. Review Manager 5.4 was used to conduct meta-analyses. Data were pooled by random-effects or fixed-effects model to obtain the mean difference (MD), risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI). Results: There were 28 eligible RCTs with a total of 2,952 participants. Overall, we verified that ZBT plus conventional therapy (CT) was superior to CT for the treatment of HLP [TC: MD = -0.50, 95% CI (-0.80, -0.19); TG: MD = -0.38, 95% CI (-0.49, -0.27); LDL-C: MD = -0.50, 95% CI (-0.69, -0.31); HDL-C: MD = 0.17, 95% CI (0.11, 0.24); total effective rate: OR = 4.26, 95% CI (2.28, 7.95)]. There were no significant differences in the primary outcomes between ZBT alone vs. CT (p > 0.05). For safety, the ZBT group (with CT or alone) outperformed the CT group [ZBT alone: RR = 0.51, 95% CI (0.32, 0.81); ZBT plus CT: RR = 0.51, 95% CI (0.30, 0.89)]. For each outcome, the subgroups and the sensitivity analysis matched the overall results. Conclusion: ZBT may be safe and beneficial to HLP patients, especially for serum lipid management. ZBT can be used along with CT for the treatment of HLP. However, it is necessary to conduct more rigorous RCTs to confirm these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022316251].

FumDSB Can Reduce the Toxic Effects of Fumonisin B1 by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs.

Fumonisin B1 (FB1) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB1 ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1 group was supplemented with FB1 at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1 group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1 can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1 were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1 by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.

Pyridoxine regulates hair follicle development via the PI3K/Akt, Wnt and Notch signalling pathways in rex rabbits.

This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism. Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0, 5, 10, 20, or 40 mg/kg pyridoxine. The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or Akt), Wnt, Notch and bone morphogenetic protein (BMP) signalling pathways were measured. In addition, free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth. Furthermore, dermal papilla cells (DPC) were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3K/Akt, Wnt, Notch and BMP signalling pathways. The results showed that the addition of dietary pyridoxine significantly increased the total follicle density, secondary follicle density, and secondary-to-primary ratio (S/P, P < 0.05), that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium, and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group (P < 0.05). In addition, pyridoxine changed the DPC cycle progression and promoted cell proliferation, and appropriate concentrations of pyridoxine (10 and 20 µmol/L) significantly inhibited cell apoptosis (P < 0.05). Pyridoxine significantly affected the gene expression of components of the PI3K/Akt, Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits (P < 0.05), increased the levels of phosphorylated catenin beta 1 (CTNNB1) and Akt, and decreased the level of phosphorylated glycogen synthase kinase 3 beta (GSK-3ß) (P < 0.05). Therefore, the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3K/Akt, Wnt and Notch signalling pathways, prolonging hair follicle growth and delaying the onset of telogen.

LC-MS/MS determination of ginsenoside compound K and its metabolite 20 (S)-protopanaxadiol in human plasma and urine: applications in a clinical study.

AIM: Ginsenoside compound K (CK) is considered to be a potential therapeutic drug for rheumatoid arthritis because of its good anti-inflammatory activity. The purpose of this work was to establish a rapid, sensitive and specific method for determination of CK and its active metabolite 20(S)-protopanaxadiol (20(S)-PPD). Materials & methods: The analytes and internal standards were extracted by liquid-liquid extraction. Then, were separated by high performance liquid phase and determined by triple quadrupole mass spectrometry. RESULTS: A LC-MS/MS using liquid-liquid extraction was developed for determining CK over the concentration range 1.00-1002.00 ng/ml and 0.15-54.30 ng/ml for 20(S)-PPD. The lower limits of quantification for CK and 20(S)-PPD were 1.00 and 0.15 ng/ml, respectively. CONCLUSION: This method was successfully validated for detecting both CK and 20(S)-PPD in the human plasma and urine, and was proved to be suitable for the pharmacokinetic study of CK in healthy Chinese volunteers. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-14004824.

Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors.

A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.

Effects of Maydis stigma polysaccharide on the intestinal microflora in type-2 diabetes.

CONTEXT: Diabetes is a serious endocrine and metabolic disorder. Food supplements attract people's attention in mitigating health problems from the aspect of gastrointestinal microflora. Maydis stigma (Zea mays subsp. mays L. [Poaceae]), has been used as water decoction for treating diabetes in folk medicine. It has great potential, and feasibly a stable form of Maydis stigma commercial products could be developed to fulfil the health food market. OBJECTIVE: To study the effects of Maydis stigma polysaccharide (MSP) on the intestinal microflora in type-2 diabetes (T2D). MATERIALS AND METHODS: MSP was fractioned from Maydis stigma by distilled water, purified by DEAE-52 Cellulose chromatography and Sephadex G-200 gel column. Streptozotocin (160 mg/kg) was intraperitoneal injected for 3 days to build model. The diabetic mice were randomly divided into five groups together with control group (10 mice in each group). The doses of MSP were 400, 600 and 800 mg/kg, respectively. After 5 weeks of administration, antidiabetic effects and intestinal microflora balance restoring activities were evaluated by denaturing gradient gel electrophoresis. RESULTS: Blood glucose levels of MSP-treated groups showed extremely significant hypoglycemic effects (p < 0.01), body weight increased showed extremely significant (p < 0.01) differences. Bacteroides, Lactobacillus and Prevotella were dominant organisms in the intestinal tract. The quality and quantity of Lactobacillus and Bacteroides genus increased remarkably with increasing concentration of MSP. DISCUSSION AND CONCLUSION: Experimental results of this study suggest that MSP has the significant potential to be used as a natural agent for treating T2D and restoring the intestinal microflora balance.

Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1-ERK signaling pathway.

The aerial parts of Saururus chinensis (Lour.) Baill are a Chinese herbal medicine used for the treatment of edema and inflammatory diseases. However, the effect of this medicine on enterovirus 71 (EV71) infection has not been explored. Previous studies showed that MEK1-ERK signal pathway was required for efficient replication of EV71 infection and inhibition of this signal pathway has been shown to suppress virus infection. Here we show that the water extract of S. chinensis (Lour.) Baill (SCB) significantly blocks EV71 infection by inhibiting the activation of MEK1-ERK signal pathway with an IC50 of 8.9µg/mL. SCB at 30 and 60 µg/mL blocked EV71-induced cytopathic effect (CPE) and production of infectious virion by 1.9 and 5.1 logs, respectively. Virucidal assay suggested that SCB had no virucidal activity against EV71 and probably exerted its effect by targeting multiple steps in EV71 infection. Knockdown of MEK1 but not MEK2 blocked EV71 replication. And SCB treatment inhibited the activation of MEK1-ERK signal during EV71 infection. Furthermore, we found that rutin at 200 µM, one of the major components of SCB, significantly suppressed EV71 induced CPE and inhibited viral replication in a dose dependent manner. Taken together, SCB inhibited EV71 infection by hijacking MEK1-ERK signal pathway and rutin was the responsible antiviral component of SCB.

Effects of cordycepin on Y-maze learning task in mice.

Cordycepin (3'-deoxyadenosine) is the major bioactive component of Cordyceps militaris that has been widely used in oriental countries as a Traditional Chinese Medicine and healthy food for preventing early aging, improving physical performance and increasing lifespan. Cordyceps militaris extracts other than cordycepin have been reported to improve cognitive function. Although cordycepin is one of the most utilized Cordyceps militaris components, it remains unknown whether cordycepin could improve learning and memory. Here we investigated effects of cordycepin on learning and memory in healthy and ischemic mice using Y-maze test. We found that oral cordycepin administration at dose of 10 mg/kg significantly improved Y-maze learning performance both in healthy and ischemic mice. However, cordycepin at dose of 5 mg/kg enhanced Y-maze learning only in ischemic mice but not healthy mice. In this study, simultaneously, we found that orally administrated cordycepin significantly decreased the neuronal loss induced by ischemia in hippocampal CA1 and CA3 regions. Collectively, our results can provide valuable evidence that cordycepin may act as a nootropic product or potential clinical application in improving cognitive function of patients with ischemic stroke in the future.

Tenuigenin ameliorates learning and memory impairments induced by ovariectomy.

Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction.

A laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease.

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC50 (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 µ g/mL and 20.6 µ g/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC50 value of 70.3 µ g/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD.

Tenuigenin treatment improves behavioral Y-maze learning by enhancing synaptic plasticity in mice.

Polygala tenuifolia root has been used to improve memory and cognitive function in Traditional Chinese Medicine for more than 2000 years. Since tenuigenin (TEN) is one of the most utilized P. tenuifolia root extracts, it is surprising there is no evidence for the effects of TEN on learning and memory so far. In the present study, we investigated the effects of TEN on learning and memory with Y-maze test in mice. We found that oral administration of 4mg/kg TEN significantly improved learning and memory in Y-maze task. Treatment with 4mg/kg TEN markedly reduced the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity in hippocampus. In the electrophysiological test of hippocampal brain slice, 2µg/ml TEN perfusion substantially enhanced field excitatory postsynaptic potential (fEPSP) amplitude both in basic synaptic transmission and after high frequency stimulation (HFS) in Schaffer to CA1 pathway (Scha-CA1). These results indicate that TEN enhancing learning and memory may result from inhibiting AChE activity, improving antioxidation and enhancing synaptic plasticity in mice. Therefore, TEN shows promise as a potential nootropic product in improving learning and memory.

[Clinical efficacy of Yougui capsules and Wuziyanzong pills on oligoasthenospermia].

OBJECTIVE: To investigate the clinical effects of the Chinese traditional medicine Yougui Capsules and Wuziyanzong Pills on sperm viability and motility in patients with oligoasthenospermia. METHODS: A total of 80 infertile men oligoasthenospermia were equally randomized into a trial and a control group, the former treated with Yougui Capsules at 1.68 g tid, while the latter with Wuziyanzong Pills at 6 g bid, both for a course of 12 weeks. The sperm viability and motility of the patients were detected and compared before and after medication. RESULTS: After 12 weeks of medication, the sperm viability and percentages of grade a and grade a + b sperm were (65.7 +/- 13.1), (22.5 +/- 9.1) and (47.6 +/- 15.8)% in the trial group, significantly higher than (38.1 +/- 11.1), (13.2 +/- 6.8) and (24.1 +/- 10.9)% in the control (P<0.05). What's more, the above three parameters of the two groups were also significantly higher than those before medication, which were (31.9 +/- 16.9), (8.2% +/- 3.7) and (15.7 +/- 13.9)% in the former and (31.7 +/- 17.0), (7.9 +/- 4.5) and (16.9 +/- 13.6)% in the latter (P<0.05). CONCLUSION: Both Yougui Capsules and Wuziyanzong Pills can improve sperm viability and motility in patients with oligoasthenospermia, and the former is even more efficacious than the latter.

[Acupuncture for chronic prostatitis: a meta-analysis].

OBJECTIVE: To determine the effect of acupuncture on chronic prostatitis. METHODS: We retrieved all the case-control studies on acupuncture for chronic prostatitis before August 2007 in MEDLINE and CNKI databases, screened the eligible literature according to the selection and exclusion criteria, and performed meta-analyses of the included studies with the software Revman 4. 2. RESULTS: Thirteen eligible reports were identified in this study, including 861 cases and 738 controls. The effectiveness and cure rates were significantly higher in the acupuncture therapy group than in the control, with pooled RR as 1.20 (95% CI, 1.14, 1.25; P < 0.01) and 1.85 (95% CI, 1.63, 2.11; P < 0.01), respectively. CONCLUSION: Acupuncture therapy exhibited a definite effect in the treatment of chronic prostatitis.

Acupuncture therapy for experimental stomach ulcer and c-Fos expression in rats.

AIM: To determine the role of acupuncture therapy in treating experimental gastric ulcer in rats. METHODS: Twenty-eight adult male Sprague-Dawley rats were randomly divided into four groups (pre-acupuncture group; acupuncture group; paradistance-acupuncture group; and control group), and pre-acupuncture, paradistance-acupuncture, and control groups received 5 muL acetic acid (200 mL/L HAc) injection after a same course of electroacupuncture (EA) treatment (4 Hz, 0.6 mA, 0.45 ms, 45 min for 4 d). The rats in these three groups recovered within 4 d. The acupuncture group received EA therapy for 4 d, after HAc injection. The stomach was dissected to compare the pathological structures of ulcer. Also c-Fos activation in the nuclei of solitary tract (NTS) was observed under microscope after regular immunohistochemistry staining of brain stem sections. RESULTS: The number of ulcers was different among the four groups, especially between control group and paradistance-acupuncture group or pre-acupuncture group. In the latter group, the number of ulcers was much less. The gastric ulcer area was consistent with the histopathological results, indicating that pre-acupuncture had an obvious therapeutic effect on gastric ulcers. Acupuncture had a very modest effect and paradistance-acupuncture had no effect on gastric ulcers. No therapeutic effect was found in the control group. Fos-Li neurons in NTS induced by noxious gastric ulcer showed a significant difference between pre-acupuncture and control groups. CONCLUSION: Acupuncture before ulceration can obviously alleviate ulcer. The production of c-Fos proves that the vagus nerve mediates the induction of c-Fos in nuclei of solitary tract following experimental ulceration, suggesting that parasympathetic afferents promote the process of noxious visceral stimulation.

[Description and histology identification of several algae of Sargassum sp].

This paper reported the description characters and microscopical identification of seven kinds of algae of Sargassum sp., Sargassum pallidum (Tum.) C. Ag., S. fusiforme (Harv.) Setch., S. horneri (Tum.) C. Ag., S. hemiphyllum (Turh.) C. Ag., S. thunbergii (Mert.) O'Kuntze, S. polycystum C. Ag. and S. kjellmanianum Yendo. The results revealed that there were clear differences in the description characters and microscopical identification of the seven kinds of algae of Sargassum sp. These studies provided a scientific basis for distinguishing crude drug of algae, developing and making use of alga natural resources of Sargassum sp.