TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine.

The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with "herb-compound-target-pathway" and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub ( https://github.com/yangpluszhu/tcmnpas ), and the project is freely available at http://54.223.75.62:3838/ .

Differences in Contents and Formation Methods of Clinical Questions in Chinese and Korean Clinical Practice Guidelines of Acupuncture-Moxibustion: Scoping Review.

OBJECTIVE: To analyze the differences in the needs of users and the value orientation of clinical practice guidelines (CPGs) by comparing the contents and formation methods of clinical questions in Chinese and Korean CPGs of acupuncture-moxibustion (Acup-Mox). METHODS: The full text of CPGs was systematically searched from the official websites of Chinese and Korean traditional medicine societies and Acup-Mox associations, with the topic "Acup-Mox for treating diseases" and the retrieval time up to September 28, 2022. Two researchers screened the CPGs independently, and extracted the guidelines' topics, content, quantity and formation methods of clinical questions. The quantitative data were collected by counting the frequency, and the qualitative data were classified and described by thematic analysis. RESULTS: A total of 29 guidelines were included in this study, including 20 Chinese guidelines (305 questions) and 9 Korean guidelines (223 questions). The differences lie in the aspects of content and diversity, and formation method. As for content and diversity, Chinese guidelines focused mainly on the questions related to treatment such as the operation of specific intervention (86, 28.2%), efficacy of intervention (78, 25.6%), and also involving questions in diagnosis, prevention, and prognosis. While the clinical questions in Korean guidelines were concentrated to efficacy of intervention (218, 97.8%). As for formation method, in Chinese guidelines, questions were usually collected directly from clinicians, and then determined and optimized by experts. In Korean guidelines, frequently used clinical Acup-Mox interventions would be screened first. Then the expert group would set up corresponding intervention control measures so as to form clinical questions related to treatment efficacy. CONCLUSIONS: The differences reflect the different needs of clinical practitioners, and the different aims or concepts in developing Acup-Mox guidelines between China and South Korea. Chinese guidelines emphasized promoting operation protocols and techniques of Acup-Mox for practical use, while Korean guidelines emphasized promoting the frequently used clinical intervention therapies. It is speculated that the guidelines from these two countries would play different roles in guiding clinical operation and supporting medical decision. In terms of formation methods of clinical questions, it is suggested to attach importance to optimizing process in formatting clinical questions to improve the clinical applicability of CPGs of Acup-Mox.

Discussion on Collection of Clinical Questions in International Clinical Practice Guidelines of Acupuncture-Moxibustion.

The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox intervention measures, but also the operational elements of Acup-Mox. This paper aimed to put forward the idea and process of collecting clinical questions in developing international acupuncture clinical practice guidelines. The experience was collected and the idea of collecting clinical questions of Acup-Mox was formed through expert consultation and discussion in combination with expert opinions. Based on the characteristics of Acup-Mox discipline. This paper put forward the thinking of collecting elements of clinical questions following the intervention-population-outcome-control (I-P-O-C) inquiry process, according to the discipline of Acup-Mox. It was emphasized that in the process of collecting clinical questions, "treatable population" and "alleviable outcome indicators" for a specific Acup-Mox intervention with certain therapeutic effect should be focused on, so as to highlight the pertinence of clinical questions of Acup-Mox guidelines in terms of population and outcome elements.

Potential molecular mechanism of Guiqi Baizhu Decoction in radiation-induced intestinal edema by regulating HIF-1a, AQP4 and Na+/K+-ATPase.

BACKGROUND: Guiqi Baizhu Decoction (GQBZD) has a good protective effect on radiation-induced intestinal edema (RIIE). However, the underlying molecular mechanisms need further elucidation. PURPOSE: To reveal the potential mechanism of RIIE and GQBZD treatment. METHODS: SD rats were irradiated with 6Gy X-ray to establish RIIE model. The general condition of the rats was observed; the dry/wet weight ratio of colon tissue was detected; the morphological changes of colon tissue were observed by HE staining; the expressions of ROS, HIF-1α and AQP4 in colon tissue were detected by confocal laser scanning; the expression of edema-related proteins was detected by Western blot. In addition, human colon epithelial cells (NCM460) was irradiated with 2Gy X-ray, and HIF-1α expression in NCM460 was knocked down by small interfering RNA (siRNA) transfection, and the activity of Na+/K+-ATPase was detected by enzyme activity kit; the ROS expression was detected by flow cytometer; the AQP4 expression was detected by laser confocal microscopy; and the expression of edema-related proteins were detected by Western blot. RESULTS: We found that after irradiation, the colon tissue of rats was significantly edema, mainly manifested as mucosal and submucosal edema, and the ultrastructure was reflected in the structural damage of nucleus and mitochondria. ROS, HIF-1α and AQP4 were significantly expressed, and Na+/K+-ATPase expression/activity was decreased. After the intervention of GQBZD, the edema of the colon tissue of the rats was improved, the expressions of ROS, HIF-1α and AQP4 were decreased, and the expression/activity of Na+/K+-ATPase was increased. CONCLUSION: Ionizing radiation (IR) can cause significant intestinal edema. AQP4 and Na+/K+-ATPase are the key factors of RIIE, which are regulated by ROS and HIF-1α. GQBZD can improve hypoxia and oxidative stress, regulate the expression of AQP4 and Na+/K+-ATPase, and achieve a protective effect on RIIE. This study is the first to reveal the mechanism of RIIE.

Comparative pharmacokinetic studies of five C-glycosylflavones in normal and urolithiasis model rats following administration of total flavonoids from Desmodium styracifolium by liquid chromatography-tandem mass spectrometry.

The total flavonoids of Desmodium styracifolium are the flavonoid extracts purified from Desmodii Styracifolii Herba, which has conventionally been used for treating urolithiasis in China. In this study, a sensitive and simple liquid chromatography-tandem mass spectrometry method was developed to simultaneously determine five active components of the extracts in rat plasma. Chromatographic separation of the analytes (schaftoside, vicenin-1, vicenin-2, vicenin-3, and isovitexin) was performed on an ACQUITY UPLC HSS T3 Column under gradient elution conditions. The calibration curves were linear over ranges from 0.5 to 100 ng/ml for schaftoside, vicenin-1, vicenin-2, and vicenin-3, and 0.2-20 ng/ml for isovitexin. The relative standard deviation of intra- and inter-day precisions were ≤6.8% and ≤8.3%, respectively, and the accuracies (relative error) were within ±7.6%. The recoveries of the analytes ranged between 97.3% and 100.3%, and the matrix effects ranged from 98.6% to 113.8%. The method was successfully applied to the pharmacokinetic studies of the five active ingredients of Desmodium styracifolium, for the first time, in both normal and urolithiasis model rats. Results revealed that the plasma levels of these components were significantly increased under the pathological state. This study provided valuable information facilitating the clinical investigation of this medicine.

[Analysis and thought on reaching the consensus during the development of acupuncture and moxibustion clinical practice guidelines in China].

Based on the 28 Chinese clinical practice guidelines of acupuncture and moxibustion, this study summarized and analyzed the contents related to reaching consensus during the development process. The results indicated that all the 28 guidelines reported they have used consensus in the "recommendations" section, and provided details on consensus personnel, consensus methods, consensus process and consensus materials. However, it was found that the reporting of consensus was in need of further improvement. The limitations included unclear definition and responsibilities of "expert group", obscure concept between "consensus meeting" and "expert discussion", non-rigorous process of reaching consensus when generating recommendations and lacking of detailed reporting of the consensus reaching process. As such, we suggested that future researchers should conduct researches to further standardized the consensus process when developing acupuncture and moxibustion clinical practice guidelines, so as to improve the quality and clinical applicability of guidelines．.

Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells.

Breast cancer is a major threat to women's health and estrogen receptor-positive (ER+) breast cancer exhibits the highest incidence among these cancers. As the primary estrogen, estradiol strongly promotes cellular proliferation and radiotherapy, as a standard treatment, exerts an excellent therapeutic effect on ER+ breast cancer. Therefore, we herein wished to explore the mechanism(s) underlying the inhibitory effects of radiation on the proliferation of ER+ breast cancer cells. We used the ER+ breast cancer cell lines MCF7 and T47D, and their complementary tamoxifen-resistant cell lines in our study. The aforementioned cells were irradiated at different doses of X-rays with or without exogenous estradiol. CCK8 and clone-formation assays were used to detect cellular proliferation, enzyme-linked immunosorbent assay (ELISA) to determine estradiol secretion, western immunoblotting analysis and quantitative real-time PCR to evaluate the expression of proteins, and immunofluorescence to track endoplasmic reticulum stress-related processes. Finally, BALB/C tumor-bearing nude mice were irradiated with X-rays to explore the protein expression in tumors using immunohistochemistry. We found that ionizing radiation significantly reduced the phosphorylation of estrogen receptors and the secretion of estradiol by ER+ breast cancer cells. CYP19A (aromatase) is an enzyme located in the endoplasmic reticulum, which plays a critical role in estradiol synthesis (aromatization), and we further demonstrated that ionizing radiation could induce endoplasmic reticulum stress with or without exogenous estradiol supplementation, and that it downregulated the expression of CYP19A through ER-phagy. In addition, ionizing radiation also promoted lysosomal degradation of CYP19A, reduced estradiol synthesis, and inhibited the proliferation of tamoxifen-resistant ER+ breast cancer cells. We concluded that ionizing radiation downregulated the expression of CYP19A and reduced estradiol synthesis by inducing endoplasmic reticulum stress in ER+ breast cancer cells, thereby ultimately inhibiting cellular proliferation.

Efficacy and safety of traditional Chinese medicine on treating oligomenorrhea: a systematic review and meta-analysis.

BACKGROUND: Oligomenorrhea is one of the most frequent gynecologic complaints that interferes with women's life quality. Treatment using traditional Chinese medicine (TCM) is a preferred alternative therapy for oligomenorrhea. However, systematic reviews (SRs) evaluating the efficacy of TCM treatments for oligomenorrhea remain absent. The present SR and meta-analysis aimed to evaluate the efficacy and safety of TCM treatment for oligomenorrhea. METHODS: Randomized controlled trials (RCTs) published in English and Chinese were retrieved by searching in the databases in October 2019, including PubMed, Cochrane Library, EMBASE, Sinomed, CNKI, VIP, and WanFang databases. Quantitative analyses and quality assessments were then conducted based on abstracted data. This study protocol is registered PROSPERO, number CRD42018095660. RESULTS: A total of 26 eligible RCTs involving 2,389 patients were included in our analysis. Overall, we observed an effect of increasing menstrual blood volumes owing to using TCM treatments plus bio-medicine (BM) (n=649; MD, 12.05; 95% CI: 5.23 to 18.87; P<0.00001; I2=96%). Besides, TCM combined with BM yielded a significant prolongation in menstrual periods (MD, 1.20; 95% CI: 0.78 to 1.62; P<0.00001; I2=76%), and had potential improvements on enhancing effectiveness rates, increasing endometrial thickness, and raising the levels of estradiol (E2) and progesterone (P). Concerning adverse events (AEs), no significant difference was found in either group. The quality of evidence was relatively low. CONCLUSIONS: This study seems to support the potential effect of TCM on treating oligomenorrhea. However, the relatively low quality of prior studies calls for future RCTs to further assess the efficacy of TCM on treating oligomenorrhea using rigorous designs.

How to rescue high-dose methotrexate induced nephrotoxicity and literature review about hemodiafiltration?

Methotrexate (MTX) is a highly renal and liver toxicity drug used in hematological malignancy treatment in children and adults. High-dose methotrexate (HD-MTX) therapy may cause impairment of kidney and decrease the elimination of MTX, at the same time, the serum concentration of MTX increased. Today the treatment for preventing MTX toxicity after renal shutdown is Carboxypeptidase. We report a patient who experienced nephrotoxicity after the HD-MTX infusions during the treatment for non-Hodgkin lymphoma (NHL) and received hemodiafiltration (HDF) with large dose of leucovorin (LV) to treat MTX intoxication. LV is very potent in the prevention of neurotoxicity and administration of LV could protect the normal cells, but the dosage and duration of LV should be according to the MTX concentration. Although a large dose of LV was applied, the patient's condition did not improve. It was found that the HDF with large dose of LV to save the patient and steadily improved the patient's clinical condition.

Guiqi Baizhu Decoction Alleviates Radiation Inflammation in Rats by Modulating the Composition of the Gut Microbiota.

The gut microbiota is important in metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with inflammation caused by ionizing radiation (IR). Guiqi Baizhu decoction (GQBZD) is a medicinal compound used in traditional Chinese medicine with anti-inflammatory and antioxidation effects, especially in the process of radiotherapy. However, the effect of GQBZD on reducing the damage to the normal immune system in radiotherapy remains unclear. Here, we show that GQBZD reduces body weights, water intake, food intake, diarrhea level and quality of life score, and inflammation and enhances immunity function in rats treated with X-ray radiation. Meanwhile, our data indicate that GQBZD not only reverses IR-induced gut dysbiosis as indicated change of α-diversity and ß-diversity of microbiota, the composition of Desulfovibrio, Bacteroides, and Parabacteroides, except for Roseburia and Lachnoclostridium, but also maintains intestinal barrier integrity and promoting the formation of short-chain fatty acids (SCFAs). GQBZD can also reduce the level of phosphorylation P65 (p-P65). Our results demonstrate that GQBZD can significantly alleviate the inflammatory responses and improve the immune damage against IR, and may be used as prebiotic agents to prevent gut dysbiosis and radiation-related metabolic disorders in radiotherapy.

[Similarities and differences between Ginkgo biloba and Panax notoginseng in treatment of ischemic cerebrovascular disease].

Ginkgo biloba and Panax notoginseng are both herb medicines for cerebrovascular disease, and play an active role in treating ischemic cerebrovascular disease(ICVD). Their mechanisms of action include antioxidant stress, nerve protection, vascular protection. According to the comparative study of literatures, G. biloba has a certain protective effect from the early stage of free radical formation throughout the whole process of causing cell inflammation and apoptosis in antioxidant stress; while P. notoginseng has mainly anti-inflammatory, anti-apoptosis effects. In the nerve protection and repair of nerve damage caused by glutamate, both could promote neurogenesis, repair damaged axons and protect nerve cells. In addition, G. biloba could also relieve neurotoxicity caused by glutamate damage, while P. notoginseng have a unique effect in repairing blood-brain barrier(BBB) and blood vessel regeneration. In clinic, they are used as auxiliary drugs in combination with thrombolytic therapy, and play curative effects in alleviating inflammation, eliminating edema, improving the cure rate and the prognosis. For cerebral diseases caused by chronic cerebral hypoperfusion, G. biloba could reduce inflammation and improve cognition. In addition, G. biloba could protect neurocyte by adjusting the secretion of dopamine in vivo, and has a certain effect on antidepressant diseases, which however needs further studies.

Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium tuberculosis in China.

BACKGROUND: The increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB. METHODS: We sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size. RESULTS: Epidemiological/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes/intergenic regions/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993-2000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis/treatment technologies and government support. CONCLUSIONS: Our findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.

Baicalin and rutin are major constituents in Shuanghuanglian injection involving anaphylactoid reaction.

OBJECTIVE: To identify the constituents in Shuanghuanglian injection (SHLI) that correlate with anaphylactoid reaction. METHODS: Chemical fingerprints of 10 batches SHLI samples were determined by High Performance Liquid Chromatography (HPLC), and further investigated by similarity analysis. Combined with optical microscopy, both anaphylactoid experiments and confirmatory assay were displayed in Rat basophil leukemia cells (RBL-2H3) to obtain the histamine release inducing by SHLI. The content of histamine was tested by Enzyme-Linked Immuno Sorbent Assay method. Partial least squares regression (PLSR) method and HPLC-DAD-ESI-MSn technology were conducted to analyze constituents in SHLI involving anaphylactoid reaction. RESULTS: The results of spectrum and effect relationships showed that the eight constituents were positively correlated with anaphylactoid reaction. Among which, nearly 90% of them were identified as baicalin and rutin with PLSR and HPLC-DAD-ESI-MSn. This result was in accordance with confirmatory assay on RBL-2H3 cells. CONCLUSION: Baicalin and rutin from SHLI were the main constituents involving anaphylactoid reaction.

In vitro evaluation of a Folate-bovine serum albumin-doxorubicin conjugate.

Doxorubicin (DOX) is one of the most effective anticancer drugs. However, its therapeutic effectiveness is greatly hampered by its dose limiting and cumulative cardiotoxic side effects. To overcome these limitations, bioconjugates of DOX were studied using bovine serum albumin (BSA) as a carrier to provide passive tumor targeting by the enhanced permeability and retention (EPR) effect. Folic acid, as an active targeting agent, was linked to BSA to increase the selectivity of the conjugate. In the present study, folate-targeted (Folate-BSA-DOX) conjugates were prepared. In the optimization process, we found that 30 mg of folic acid activated esters reacted with BSA at pH 9.8 for 1 h, the yield was maximum. The qualitative analysis of fluorescent experiments revealed that Folate-BSA-DOX can be specifically delivered to Hela cells and that this unique interaction can be blocked by 1 mM free folic acid. More importantly, the enhanced efficiency of uptake of Folate-BSA-DOX by Hela cells was coupled with the increase of the amount of the conjugate, the incubated time and the conjugated ratio of folic acid. Finally, the quantitative data obtained from the flow cytometry further verified the higher targeting and killing ability of Folate-BSA-DOX to folate receptor positive tumor cells than BSA-DOX.