Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management.

BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.

Dynamic Changes in the Microbial Community and Metabolite Profile during the Pile Fermentation Process of Fuzhuan Brick Tea.

The pile fermentation process of Fuzhuan brick tea is unique in that it involves preheating without the use of starter cultures. The detailed metabolite changes and their drivers during this procedure are not known. Characterizing these unknown changes that occur in the metabolites and microbes during pile fermentation of Fuzhuan brick tea is important for industrial modernization of this traditional fermented food. Using microbial DNA amplicon sequencing, mass spectrometry-based untargeted metabolomics, and feature-based molecular networking, we herein reveal that significant changes in the microbial community occur before changes in the metabolite profile. These changes were characterized by a decrease in Klebsiella and Aspergillus, alongside an increase in Bacillus and Eurotium. The decrease in lysophosphatidylcholines, unsaturated fatty acids, and some astringent flavan-3-ols and bitter amino acids, as well as the increase in some less astringent flavan-3-ols and sweet or umami amino acids, contributed importantly to the overall changes observed in the metabolite profile. The majority of these changes was caused by bacterial metabolism and the corresponding heat generated by it.

Administration of modified Gegen Qinlian decoction for hemorrhagic chronic radiation proctitis: A case report and review of literature.

BACKGROUND: Hemorrhagic chronic radiation proctitis (CRP) is a common late complication of irradiation of the pelvis and seriously impairs life quality. There is no standard treatment for hemorrhagic CRP. Medical treatment, interventional treatment, and surgery are available, but they are limited in their applications due to nondefinite efficacy or side effects. Chinese herbal medicine (CHM), as a complementary or alternative therapy, may provide another option for hemorrhagic CRP treatment. CASE SUMMARY: A 51-year-old woman with cervical cancer received intensity-modulated radiation therapy and brachytherapy with a total dose of 93 Gy fifteen days after hysterectomy and bilateral adnexectomy. She received six additional cycles of chemotherapy with carboplatin and paclitaxel. Nine months after radiotherapy treatment, she mainly complained of 5-6 times diarrhea daily and bloody purulent stools for over 10 d. After colonoscopy examinations, she was diagnosed with hemorrhagic CRP with a giant ulcer. After assessment, she received CHM treatment. The specific regimen was 150 mL of modified Gegen Qinlian decoction (GQD) used as a retention enema for 1 mo, followed by replacement with oral administration of 150 mL of modified GQD three times per day for 5 mo. After the whole treatment, her diarrhea reduced to 1-2 times a day. Her rectal tenesmus and mild pain in lower abdomen disappeared. Both colonoscopy and magnetic resonance imaging confirmed its significant improvement. During treatment, there were no side effects, such as liver and renal function damage. CONCLUSION: Modified GQD may be another effective and safe option for hemorrhagic CRP patients with giant ulcers.

Hippophae rhamnoides L.: A Comprehensive Review on the Botany, Traditional Uses, Phytonutrients, Health Benefits, Quality Markers, and Applications.

Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1-99), lignans (100-143), volatile oils (144-207), tannins (208-230), terpenoids (231-260), steroids (261-270), organic acids (271-297), and alkaloids (298-305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Survival of Non-small Cell Lung Cancer Patients Treated with Fuzheng Gushe Therapy： A Real World Study / 中国实验方剂学杂志

ObjectiveTo analyze the long-term survival of non-small cell lung cancer （NSCLC） patients treated with Fuzheng Gushe therapy in the real world. MethodA retrospective cohort study was carried out with the NSCLC patients treated with Fuzheng Gushe therapy from January 2014 to December 2018 in Dongzhimen Hospital， Beijing University of Chinese Medicine as the integrated traditional Chinese medicine （TCM） and western medicine cohort. The NSCLC data from January 2011 to December 2015 in the Surveillance， Epidemiology， and End Results （SEER） database were downloaded as the western medicine cohort. The propensity score matching （PSM） was employed to balance the confounding factors between the groups， and comparable samples were obtained from the two groups. The Log-rank test was conducted to compare the overall survival between the groups and the survival curves were established. ResultThe integrated TCM and western medicine cohort and the western medicine cohort included 511 and 5 022 NSCLC patients， respectively. The age， sex， and chemotherapy had no significant differences between the two cohorts， while pathological type， lymph node metastasis （N）， distant metastasis （M）， surgery， and radiotherapy were different between the two cohorts （P<0.05）. After PSM， 122 comparable samples were obtained. The overall survival analysis showed that the total survival of the integrated TCM and western medicine cohort was better than that of the western medicine cohort （P<0.05）. The stratified survival analysis showed that the integrated TCM and western medicine cohort had survival advantages in females， males， the young， and adenocarcinoma， N+， and M+ patients （P<0.05）. ConclusionFuzheng Gushe therapy can significantly improve the overall survival of NSCLC patients， especially in the females， the males， the young， and the patients with adenocarcinoma， lymph node metastasis， and distant metastasis.

Regulation of ischemic stroke by circadian rhythm and intervention by traditional Chinese medicine / 中国中药杂志

Circadian rhythm is an internal regulatory mechanism formed in organisms in response to the circadian periodicity in the environment, which modulates the pathophysiological events, occurrence and development of diseases, and the response to treatment in mammals. It significantly influences the susceptibility, injury, and recovery of ischemic stroke, and the response to therapy. Accumulating evidence indicates that circadian rhythms not only regulate the important physiological factors of ischemic stroke events, such as blood pressure and coagulation-fibrinolysis system, but also participate in the immuno-inflammatory reaction mediated by glial cells and peripheral immune cells after ischemic injury and the regulation of neurovascular unit(NVU). This article aims to link molecular, cellular, and physiological pathways in circadian biology to the clinical consequences of ischemic stroke and to illustrate the impact of circadian rhythms on ischemic stroke pathogenesis, the regulation of NVU, and the immuno-inflammatory responses. The regulation of circadian rhythm by traditional Chinese medicine is reviewed, and the research progress of traditional Chinese medicine intervention in circadian rhythm is summarized to provide a reasonable and valuable reference for the follow-up traditional Chinese medicine research and molecular mechanism research of circadian rhythm.

Targets and Potential Mechanism of Scutellaria baicalensis in Treatment of Primary Hepatocellular Carcinoma Based on Bioinformatics Analysis.

OBJECTIVE: To analyze the target and potential mechanism of Scutellaria baicalensis (SB) in the treatment of HCC based on bioinformatics, so as to provide suggestions for the diagnosis, treatment, and drug development of hepatocellular carcinoma (HCC). METHODS: The regulated gene targets of SB were screened by gene expression pattern clustering and differential analysis of gene expression data of HepG2 cells treated with SB at 0 h, 1 h, 3 h, 6 h, 12 h, and 24 h. The module genes related to HCC were identified by the weighted gene coexpression network analysis (WGCNA). KEGG and GO enrichment were used to analyze the molecular function and structure of the module, and GSEA was used to evaluate the different functional pathways between normal people and patients with HCC. Then, the module gene was used for univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model. The protein-protein interaction network (PPI) was used to analyze the core genes regulated by SB (CGRSB) of the module, and the survival curve revealed the CGRSB impact on patient survival. The CIBERSORT algorithm combined with correlation analysis to explore the relationship between CGRSB and immune infiltration. Finally, the single-cell sequencing technique was used to analyze the distribution of CGRSB at the cellular level. RESULTS: SB could regulate 903 genes, of which 234 were related to the occurrence of HCC. The prognosis model constructed by these genes has a good effect in evaluating the survival of patients. KEGG and GO enrichment analysis showed that the regulation of SB on HCC mainly focused on some cell proliferation, apoptosis, and immune-related functions. GSEA enrichment analysis showed that these functions are related to the occurrence of HCC. A total of 24 CGRSB were obtained after screening, of which 13 were significantly related to survival, and most of them were unfavorable factors for patient survival. The correlation analysis of gene expression showed that most of CGRSB was significantly correlated with T cells, macrophages, and other functions. The results of single-cell analysis showed that the distribution of CGRSB in macrophages was the most. CONCLUSION: SB has high credibility in the treatment of HCC, such as CDK2, AURKB, RRM2, CENPE, ESR1, and PRIM2. These targets can be used as potential biomarkers for clinical diagnosis. The research also shows that the p53 signal pathway, MAPK signal pathway, apoptosis pathway, T cell receptor pathway, and macrophage-mediated tumor immunity play the most important role in the mechanism of SB in treating HCC.

Identification and quantification analysis of the chemical constituents from Mahonia fortune using Q­Exactive HF Mass Spectrometer and UPLC-ESI-MS/MS.

In this research, a comprehensive and innovative method was established for the qualitative and quantitative analysis of the main components in Mahonia fortune (MF). On the one hand, comprehensive insight of the constituents in MF extracts was achieved with a Q­Exactive HF Mass Spectrometer using data-independent acquisition method. The identification of 17 compounds was based on comparison with authentic reference standards and the deduction of 119 additional compounds both in positive and negative modes was using the MS-dial strategy and comparison with literature data. The proportion of alkaloids and phenols were the most in MF. On the other hand, an ultra-performance liquid chromatographic-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method for the quantification of 25 components in MF extract were developed and validated. The method established provided satisfactory precision and accuracy; acceptable recovery and stability; a good linearity and a reasonable limit of detection. The MF samples from 11 different sources were detected, and relative principal component analysis were applied to discriminate these samples. The variations of Columbamine, Jatrorrhizine, Palmatine and Berberine were suggested as important indicators of MF quality. This study supplies a novel and comprehensive method for the quality evaluation of MF. This research presents a MS based analytical strategy which shows an application potential in the analysis of the chemical constituents in Traditional Chinese Medicine (TCM).

Large-scale isolation and antitumor mechanism evaluation of compounds from the traditional Chinese medicine Cordyceps Militaris.

We established a large-scale separation and purification platform to obtain kilogram amounts of natural compounds from the extraction of the fruiting bodies of C. militaris. Seven monomeric compounds, N6-(2-hydroxyethyl) adenosine (HEA), ergosterol (E), ergosta-7,22-diene-3,5,6-triol (EI), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol (ED),ergosta-7,22-dien-3ß,5α-dihydroxy-6-one (EO), (20S,22E,24R)-Eegosta-7,22-dien-3ß,5α,6ß,9α-tetraol (ET), and (24S)-5,22-stigmastadien-3ß-ol (SE), were harvested using different solvents, and the structure of each compound was identified. The activities and functions of the isolated compounds were tested by label-free, real-time cell analysis methods at the cellular level, and their antitumor effects were verified using mouse models of Lewis and H22 tumors. The anti-insomnia effect of HEA was tested in an anti-insomnia mouse model. The interactions between E and 8 A549 cell proteins were determined. The biosynthetic pathways of HEA and E, which possess pharmacologically active monomers, were determined. This platform can provide a theoretical basis for the further development and discovery of novel natural medicines.

Review on Mechanism of Multi-target Intervention of Traditional Chinese Medicine on Metabolic Syndrome / 中国实验方剂学杂志

The pathogenesis of metabolic syndrome （MS） includes insulin resistance （IR）， central obesity， chronic low-grade inflammation， oxidative stress， endoplasmic reticulum stress， elevated free fatty acid levels， intestinal flora imbalance， renin angiotensin system abnormality， and autophagy activity deficiency， etc. Most researchers believe that IR plays a central role in the pathogenesis of MS， and abdominal obesity is an important initial factor of MS. According to the incidence and clinical characteristics， MS is classified as "obesity" "pidan" " abdominal fullness " and other diseases. It is said that the pathogenesis of MS is related to the deficiency of spleen and kidney， the formation of phlegm， turbidity， blood stasis and other pathological products， which damage the body's functions of qi， blood， yin and yang. Traditional Chinese medicine （TCM） has unique advantages in treating MS based on the holistic view and syndrome differentiation concept. It has multi-level， multi-target and multi-channel treatment characteristics. It can intervene insulin signal transduction， regulate adipocyte factor secretion level， relieve oxidative stress and endoplasmic reticulum stress response， regulate intestinal flora and renin angiotensin system， reduce free fatty acid level and regulation Autophagy and other ways to improve chronic low-grade inflammation and IR status， and then comprehensive prevention and treatment of MS and its complications. However， the following problems still exist：lack of high-quality randomized controlled clinical research and large sample real-world research， clinical unified diagnosis and treatment standard has not yet formed， lack of genetic animal model in basic research， relatively single signal pathway and target of experimental research， and difficulty in timely formation of clinical transformation of scientific research achievements. Therefore， we should make full use of modern scientific and technological means to carry out systematic and standardized multicenter， large sample， high-quality randomized controlled trials or real-world research， we should prepare perfect animal models， focus on the crosstalk relationship between multiple related cell signaling pathways， and actively explore the potential relationship between signaling pathways and prescription compatibility， so as to actively promote basic scientific research achievements Clinical practice may be the key research direction in the prevention and treatment of MS in TCM.

Effect of Chinese medicine for promoting blood circulation on microvascular angina: A systematic review and meta-analysis.

BACKGROUND: Blood-activating drugs (BADs) are widely used to treat microvascular angina in China. This study aims to summarize relevant evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of BADs in the treatment of microvascular angina. METHODS: We searched for relevant studies before June 2019 from seven databases. Twenty-four studies were included of 1903 patients with microvascular angina. All studies compared the use of traditional Chinese medicine for activating blood circulation (BADs) and Western medicine (WM) with the use of Western medicine alone. RESULTS: In all, 15 trials reported a significant effect of BADs on improving clinical symptoms compared with the control treatment (P < .00001), and 8 trials reported significant effects of BADs on reducing the frequency of angina pectoris attacks compared with Western medicine treatment (P < .00001). The pooled results also demonstrated that BADs provided a significant benefit in reducing the dosage of nitroglycerin required (P = .02), the maximum range of ST-segment depression (P = .003) and the descending degree of the ST-T segment of ECG (P = .0002); prolonging the total time of treadmill exercise (P < .00001) and the time of ST-segment depression of 1 mm (P = .002); enhancing the total effective rate of Traditional Chinese Medicine (TCM) syndromes (P < .00001); improving endothelial function (P < .00001); and reducing the levels of high-sensitivity C-reactive protein (hs-CRP) (P < .00001). BAD treatment showed no statistically significant effect on the levels of TNF-a (P = .8) or IL-6 (P = .13). No severe adverse events were reported. CONCLUSION: This meta-analysis shows that BADs are effective for the treatment of microvascular angina. Although concerns regarding selective bias and low methodological quality were raised, our findings suggest that BADs are beneficial for patients with microvascular angina and should be given priority for future clinical studies.

Serum Metabolic Profiling Analysis of Gout Patients Treated with Traditional Chinese Medicine Tongfengtai Granules Based on Gas Chromatography-Mass Spectrometry.

Gout has become a public health problem that seriously threatens human health. Traditional Chinese medicines (TCMs) have a long history of treating gout and have some advantages compared with the conventional medicines. Compound TCM Tongfengtai granules are gradually being used for clinical treatment of gout, but its mechanism is still unclear. The purpose of this study was to explore the metabolic profiling of serum from gout patients before and after treatment with Tongfengtai granules and identify the differential metabolites and related metabolic pathways. A total of 40 gout patients hospitalized in Shenzhen Traditional Chinese Medicine Hospital from 2018 to March 2019 were recruited in the current study, and serum samples from these patients before and after treatment with Tongfengtai granules were collected. Gas chromatography-mass spectrometry (GC-MS) assay was used to identify serum metabolites. The OPLS-DA VIP method was used to screen for potential metabolic biomarkers, and MetaboAnalyst 4.0 was used to identify related metabolic pathways. The result showed that there was a significant difference in the concentrations of six metabolites in the serum after treatment: D-galactose, lactic acid, 3-hydroxybutyric acid, D-pyran (type) glucose, alanine, and L-isoleucine. Except D-pyran (type) glucose, the serum concentrations of the other five metabolites were all significantly reduced. Besides, pathway enrichment analysis found that these potential metabolic biomarkers were mainly involved in lactose degradation and the glucose-alanine cycle. Thus, the serum metabolic profiling of gout patients treated with Tongfengtai granules changed, and the differential metabolites and related metabolic pathways might provide clues for understanding the mechanism of Tongfengtai granules.

A meta-analysis for Kuanxiong Aerosol on the treatment of angina pectoris.

BACKGROUND: Kuanxiong Aerosol (KA) has been used in patients with angina pectoris (AP) attacks for many years, this systematic review and meta-analysis aims to evaluate the clinical efficacy and safety of KA versus nitrates in the treatment of AP. METHODS: Seven databases (PubMed, EMBASE, CENTRAL, CNKI, VIP, CBM and Wanfang) were searched from inception to November 2019 to include randomized controlled trials (RCTs) that compare the efficacy and safety of KA with nitrates on the treatment of AP. And two reviewers independently assessed the risk of bias. RESULT: A total of 12 RCTs were eventually included, involving 2001 patients. Compared with the Nitrates group, the KA group showed great significant improvement on the 3-min [relative risk (RR) = 1.12, 95% confidence interval (CI) (1.03,1.23), P < .05;11 studies,1875 patients] and 5-min [RR = 1.05, 95%CI (1.01,1.08), P < 0.05; 11 studies,1875 patients] angina remission rates, the incidence of adverse reactions [RR = 0.42,95% CI (0.33,0.54), P < 0.00001; 8 studies, 1350 patients], endothelin(ET) [SMD = -0.40, 95%CI (-0.74,-0.07), P < 0.05; 2 studies, 143 patients] and c-reactive protein (CRP) [SMD = -0.58, 95%CI (-0.87,-0.30), P < 0.00001;2 studies, 200 patients],but no significant improvement on electrocardiogram efficacy [RR = 1.03, 95%CI (0.98,1.10), P = 0.26;11 studies, 1549 patients], nitric oxide (NO) [SMD = -0.08, 95%CI (-0.61,0.45), P = 0.76;2 studies, 143 patients]. CONCLUSION: The clinical use of KA is effective and safe on the treatment of AP, which appears to be better than nitrates in terms of efficiency, adverse reactions, endothelial function and inflammatory response. Nevertheless, due to some limitations in the sample size and quality of the included studies, more high-quality RCTs were still needed for further verification.

Preventive Effect and Mechanism of Ethyl Acetate Extract of Sceptridium ternatum in Monocrotaline-Induced Pulmonary Arterial Hypertension.

OBJECTIVE: To observe the effect and molecular mechanism of ethyl acetate extract of Sceptridium ternatum (STE) on the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). METHODS: The main chemical components of Sceptridium ternatum were determined, and the effects in PAH rats were observed. A total of 140 Sprague Dawley rats were randomly and equally divided into the normal group, the model group, the Bosentan group, and the STE groups (2.5, 5, 10 g/kg) by the random number table method. The characteristic indicators of PAH were measured, and immunohistochemistry was used to observe the lung tissue of rats. Morphological changes of the lung tissue were observed under the light microscope. RESULTS: Compared with the normal group, rats in the model group showed a significant increase in right ventricular free wall thickness (RVFWT), mean pulmonary arterial pressure (mPAP), mean right ventricular pressure (mRVP), max right ventricular pressure (max RVP), weight of right ventricle (RV), and lung index (LI), while a significant decrease in pulmonary artery acceleration time (PAAT, P<0.01). Compared with the model group, rats treated with STE had a significant decrease of RVFWT, mPAP, mRVP, max RVP, and RV, while a significant increase of PAAT (P<0.01). After injection of MCT, nuclear factor- κB (NF- κB) p65 and α -smooth muscle actin (α -SMA) expression levels were up-regulated, and on the contrary, the treatment groups showed a significant down-regulation without dose-dependent trend. CONCLUSIONS: STE can relieve the PAH in rats. STE may relieve pulmonary vascular disease and pulmonary injury by down-regulating the expression of NF- κB p65 and α -SMA.

Effect of Huanglian Wendantang in Treatment of Metabolic Syndrome / 中国实验方剂学杂志

Metabolic syndrome (MS) is a pathological condition characterized by central obesity, insulin resistance, hypertension, and hyperlipidemia. With the increase of poor dietary habits and lifestyles in modern society, especially the poor living habits of sedentariness and less movement, the prevalence of MS has increased year by year. According to relevant data, the number of MS patients worldwide will reach about 2.568 billion by 2040, which will seriously endanger human life and health. Huanglian Wendantang, as a famous traditional Chinese medicine prescription for clearing away heat and drying dampness, regulating Qi and resolving phlegm, and benefiting the stomach and gall, has been proved to have significant pharmacological effects in lowering blood fat, reducing blood sugar and resisting inflammation by modern pharmacological studies, and widely used in the treatment of metabolic diseases, cardiovascular diseases and other systemic diseases. In recent years, a large number of studies have proved that Huanglian Wendantang has a significant effect on MS. In terms of clinical efficacy, it could significantly improve the pathological state of obesity, dyslipidemia, abnormal glucose metabolism and hypertension in MS patients. Meanwhile, it could also interfere with the inflammatory state, prethrombotic state, abnormal vascular regulation and other potential risk factors in the body, with a high safety and fewer side effects. In terms of experimental study, it could enhance the insulin sensitivity, and improve the insulin resistance of MS animal models and cell models through interventions in insulin signal transduction, inflammatory response, and antioxidant stress. By retrieving PubMed, CNKI, Weipu, Wanfang and other databases, the author summarized the study reports of Huanglian Wendantang on MS in recent years in three aspects: theoretical study, clinical efficacy study and experimental mechanism study, in the expectation of provide some scientific references for in-depth study of the mechanism of Huanglian Wendantang in treating MS and the development and clinical promotion of the prescription.

Palmatine: A review of its pharmacology, toxicity and pharmacokinetics.

Palmatine is a natural isoquinoline alkaloid and has been widely used in pharmaceutical field. The purpose of this review is to provide the latest and comprehensive information on the pharmacology, toxicity and pharmacokinetics of palmatine in the past, to explore the therapeutic potential of this compound and look for ways to reduce toxicity. Information on palmatine was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library and Europe PMC using a combination of keywords including "pharmacology", "toxicology", "pharmacokinetics". All studies of this genus were included in this review until March 2019. Palmatine has a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, anti-bacterial, anti-viral and regulating blood lipids. However, palmatine has obvious DNA toxicity, and has a complex effect on metabolic enzymes in the liver. Pharmacokinetic studies have demonstrated that glucuronidation and sulfation are the main metabolic pathways of palmatine. Palmatine can be used in many diseases. Future research directions include: how the concentration of palmatine affects pharmacological effects and toxicity; the mechanism of synergy between palmatine and other protoberberine alkaloid; Structural modification of palmatine is one of the key methods to enhance pharmacological activity and reduce activity.

Comparative analysis of vertebral transcriptome in Japanese seabass (Lateolabrax japonicus) fed diets with varying phosphorus/calcium levels.

Aquaculture jeopardizes the aquatic environment by discharge of the most dietary phosphorus (P) into the water. Reducing the dietary P level is a common approach for decreasing the P discharge but it may result in increased risk of P deficiency leading to vertebral deformities. However, the molecular mechanism of vertebral deformities is poorly understood. We assessed vertebral transcriptome and compared the genes associated with bone metabolism in Japanese seabass (Lateolabrax japonicus) fed three diets containing different P and Ca levels including: diet I (0.4% P, 0.3% Ca), diet II (0.8% P, 0.3% Ca) and diet III (0.8% P, 3% Ca). The results showed that P deficiency reduces the ossification of vertebrae and induces visible vertebral deformities. Moreover, 256 gens were up-regulated and 125 genes were down-regulated in fish fed P deficient diets. Furthermore, administration of the diet with adequate P and Ca excess (diet III) resulted in the significant enhancement in expression of 19 genes and reduced expression of 93 genes. Comparing group II with group III, expression of 109 genes was up-regulated and expression of 1369 genes was down-regulated. Gene ontology enrichment analysis revealed significant alterations in biological functions by P deficiency. In summary, these findings indicated that both dietary P shortage and Ca excess lead to reduced differentiation and proliferation of osteoblast and induce a higher activity of osteoclastogenesis, which could subsequently impair vertebral mineralization and cause skeletal deformities.

The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response Against Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals.