Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. AIM OF THE STUDY: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. METHODS: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. RESULTS: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCß, IKKß, GSK3ß, c-Fos and NF-κB p65 proteins. CONCLUSION: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload.

Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management.

BACKGROUND: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers. AIM: To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. METHODS: We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved. RESULTS: We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80-0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas. CONCLUSION: This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Exploring progress in iron supplement formulation approaches for treating iron deficiency anemia through bibliometric and thematic analysis.

Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia.

The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Analysis of drug-induced interstitial lung disease caused by herbal medicine using the Japanese Adverse Drug Event Report database.

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a severe adverse event leading to morbidity and mortality. This study evaluated the adverse event indicators of DIILD and time-to-onset profiles following the daily intake of herbal drugs (Scutellariae radix ["ogon" in Japanese], Bupleuri radix ["saiko" in Japanese], and Pinelliae tuber ["hange" in Japanese]) using the Japanese Adverse Drug Event Report database. DIILD was defined in accordance with the Medical Dictionary for Regulatory Activities. METHODS: The Japanese Adverse Drug Event Report database contained 830,079 reports published between April 2004 and April 2023. The association between herbal medicines and DILLD was evaluated using the pharmacovigilance index as the reporting odds ratio (ROR), logistic regression models, propensity score-matching techniques, and Weibull shape parameters. RESULTS: The adjusted RORs using multivariate logistic regression models for Scutellariae radix (daily intake), Pinelliae tuber (daily intake), sex (male), age (≥ 60 years), Scutellariae radix (daily intake)*age (≥ 60 years), and Scutellariae radix (daily intake)* Pinelliae tuber (daily intake) were 1.47 (1.36 - 1.59), 1.05 (1.01 - 1.10), 1.45 (1.34 - 1.57), 1.92 (1.74 - 2.11), 3.35 (3.12 - 3.60), and 1.49 (1.46 - 1.53), respectively. DIILD onset profiles were evaluated using the Weibull shape parameter. A logistic plot of daily intake and onset of DIILD was drawn. ROR signals were detected in 32 of 54 herbal medicines, including Scutellariae radix, Bupleuri radix, and Pinelliae tuber. The median duration (days) (interquartile range) to DIILD onset was 36.0 (27.0-63.0) for Saikokaryukotsuboreito, 35.0 (21.0-55.0) for Saireito, and 31.0 (13.5-67.5) for Shosaikoto. The Weibull shape parameter beta (95% confidence interval) values for Saikokaryukotsuboreito, Saireito, and Shosaikoto were 1.36 (1.08-1.67), 1.36 (1.20-1.52), and 1.31 (0.98-1.68), respectively. CONCLUSIONS: DIILD demonstrated a dose-dependent to crude drugs. Clinicians should strive for the early detection of DIILD and avoid the inadvertent administration of herbal medicines.

TCMSSD: A comprehensive database focused on syndrome standardization.

BACKGROUD: Quantitative and standardized research on syndrome differentiation has always been at the forefront of modernizing Traditional Chinese Medicine (TCM) theory. However, the majority of existing databases primarily concentrate on the network pharmacology of herbal prescriptions, and there are limited databases specifically dedicated to TCM syndrome differentiation. PURPOSE: In response to this gap, we have developed the Traditional Chinese Medical Syndrome Standardization Database (TCMSSD, http://tcmssd.ratcm.cn). METHODS: TCMSSD is a comprehensive database that gathers data from various sources, including TCM literature such as TCM Syndrome Studies (Zhong Yi Zheng Hou Xue) and TCM Internal Medicine (Zhong Yi Nei Ke Xue) and various public databases such as TCMID and ETCM. In our study, we employ a deep learning approach to construct the knowledge graph and utilize the BM25 algorithm for syndrome prediction. RESULTS: The TCMSSD integrates the essence of TCM with the modern medical system, providing a comprehensive collection of information related to TCM. It includes 624 syndromes, 133,518 prescriptions, 8,073 diseases (including 1,843 TCM-specific diseases), 8,259 Chinese herbal medicines, 43,413 ingredients, 17,602 targets, and 8,182 drugs. By analyzing input data and comparing it with the patterns and characteristics recorded in the database, the syndrome prediction tool generates predictions based on established correlations and patterns. CONCLUSION: The TCMSSD fills the gap in existing databases by providing a comprehensive resource for quantitative and standardized research on TCM syndrome differentiation and laid the foundation for research on the biological basis of syndromes.

Trend in the Incidence of Severe Partial Edentulism among Adults Using the Korean National Health Insurance Service Claim Data, 2014-2018.

PURPOSE: Missing teeth is one of the most important indicators of oral health behavior and the result of dental caries, periodontal disease, and injuries. This study examined a trend in the incidence of severe partial edentulism (SPE) using the Korean National Health Insurance Service (KNHIS) data. MATERIALS AND METHODS: Data of adults aged ≥20 years were obtained from the KNHIS for the 2014-2018 period. SPE was defined in dental information within a population with a treatment history of dental scaling as having 1 to 8 natural teeth. Crude incidence rates (CIRs) and age-standardized incidence rates (AIRs) with 95% confidence interval were calculated per 100000 persons. The Cochran Armitage trend (CAT) test and average annual percentage change were used to analyze SPE trends. RESULTS: The CIRs among Korean adults were from 346.29 to 391.11 in 2014-2016 and from 391.11 to 354.09 in 2016-2018. The AIRs trend statistically increased by 4.31% from 346.29 to 376.80 and decreased by 4.72% from 376.80 to 342.10. The AIRs in men increased by 4.00% and decreased by 3.01%. The AIRs in women decreased by 2.18% and increased by 2.11% (CAT; p<0.01). The AIRs by region and income also showed trends of increase and decrease. CONCLUSION: The study showed that the incidence trend of SPE increased and decreased from 2014 to 2018. This result would be able to aid in the planning of public oral health, and may also serve as fundamental data for verifying the impact of the public oral health policies implemented.

[Optimal search conditions for identification of patients with chronic myeloid leukemia from Japanese National Health Insurance data].

This study investigated which conditions could be used to identify patients with chronic myeloid leukemia (CML) from a National Health Insurance claims dataset. During April 2012 and September 2018, 1,789,462 employees were enrolled in the dataset for Shizuoka Prefecture residents. The number of patients with the ICD-10 code for CML was 761. Among them, 246 who had been prescribed a tyrosine kinase inhibitor were considered as having true CML. The positive predictive value was calculated as 32.3% when CML was identified by ICD-10 code alone. Combination of ICD-10 code with prescribed drugs was required to accurately identify patients with CML from the insurance database.

Prediction of protein-ligand binding affinity via deep learning models.

Accurately predicting the binding affinity between proteins and ligands is crucial in drug screening and optimization, but it is still a challenge in computer-aided drug design. The recent success of AlphaFold2 in predicting protein structures has brought new hope for deep learning (DL) models to accurately predict protein-ligand binding affinity. However, the current DL models still face limitations due to the low-quality database, inaccurate input representation and inappropriate model architecture. In this work, we review the computational methods, specifically DL-based models, used to predict protein-ligand binding affinity. We start with a brief introduction to protein-ligand binding affinity and the traditional computational methods used to calculate them. We then introduce the basic principles of DL models for predicting protein-ligand binding affinity. Next, we review the commonly used databases, input representations and DL models in this field. Finally, we discuss the potential challenges and future work in accurately predicting protein-ligand binding affinity via DL models.

Intelligent chemical profiling of 73 edible flowers by liquid chromatography-high resolution mass spectrometry combined with HRMS database and their authentication based on large-scale fingerprints.

A commercial high-resolution MS database "TCM-PCDL" was innovatively introduced to automatically identify multi-components in 73 edible flowers rapidly and accurately by liquid chromatography-high resolution mass spectrometry, which can be time-consuming and labor-intensive in traditional manual method. The database encompasses over 2565 natural products with various energy levels. Unknown compounds can be identified through direct matching and scoring MS2 spectra with database. A total of 870 compounds were identified from 73 flowers, with polyphenols constituting up to 75%. Focusing on polyphenols, a high performance liquid chromatography (HPLC) method was developed to generate fingerprints from 510 batches, establishing an "HPLC database" that enabled accurate authentication using similarity scores and rankings. This method demonstrated an accuracy rate of 100% when applied to 30 unknown samples. For flowers prone to confusion, additional statistical analysis methods could be employed as aids in authentication. This study provides valuable insights for large-scale sample chemical profiling and authentication.

Comprehensive Characterization of Triterpene Saponins in Rhizoma Panacis Japonici by Offline Two-Dimensional Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.

Rhizoma Panacis Japonici (RPJ) is an ancient herbal medicine from China that has long been employed for its medicinal benefits in relieving arthritis physical debility and diverse afflictions. The primary bioactive constituents found in RPJ are triterpene saponins, which exhibit numerous pharmacological actions, including anti-inflammatory, antioxidant, and immunomodulating effects. The present study established a straightforward and effective approach for characterizing triterpene saponins in RPJ. An offline HILIC × RP LC/QTOF-MS method was developed, along with a self-constructed in-house database containing 612 saponins reported in the Panax genus and 228 predicted metabolites. The approach achieved good chromatographic performance in isolating triterpene saponins of RPJ, with the HILIC column as the first dimension (1D) and the BEH C18 column as the second dimension (2D). The developed two-dimensional liquid chromatography system exhibited an orthogonality of 0.61 and a peak capacity of 1249. Detection was performed using a QTOF mass spectrometer in a data-independent manner (MSE) in a negative ion mode. Using the in-house database, the collected MS data were processed by an automatic workflow on UNIFI 1.8.2 software, which included data correction, matching of precursor and product ions, and peak annotation. In this study, 307 saponins were characterized from RPJ and 76 saponins were identified for the first time in Panax japonicus. This research not only enhances our understanding of the chemical characteristics of RPJ but also offers a simple and efficient method for analyzing the complex composition of herbal medicine.

Usage Patterns of Traditional Chinese Medicine for Patients with Bipolar Disorder: A Population-Based Study in Taiwan.

BACKGROUND: Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. METHODS: Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t-test was used for continuous variables. A p-value less than 0.05 indicated significance. RESULTS: One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae. CONCLUSIONS: Physicians need to be aware of the use of TCM in patients with BD.

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study.

OBJECTIVE: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA). DESIGN: A propensity score-matched cohort study. SETTING: A nationwide population-based study. PARTICIPANTS: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan. INTERVENTIONS: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort. PRIMARY OUTCOME MEASURES: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models. RESULTS: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities. CONCLUSIONS: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA.

Validating core therapeutic targets for osteoporosis treatment based on integrating network pharmacology and informatics.

OBJECTIVE: Our goal was to find metabolism-related lncRNAs that were associated with osteoporosis (OP) and construct a model for predicting OP progression using these lncRNAs. METHODS: The GEO database was employed to obtain gene expression profiles. The WGCNA technique and differential expression analysis were used to identify hypoxia-related lncRNAs. A Lasso regression model was applied to select 25 hypoxia-related genes, from which a classification model was created. Its robust classification performance was confirmed with an area under the ROC curve close to 1, as verified on the validation set. Concurrently, we constructed a ceRNA network based on these genes to unveil potential regulatory processes. Biologically active compounds of STZYD were identified using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database. BATMAN was used to identify its targets, and we obtained OP-related genes from Malacards and DisGeNET, followed by identifying intersection genes with metabolism-related genes. A pharmacological network was then constructed based on the intersecting genes. The pharmacological network was further integrated with the ceRNA network, resulting in the creation of a comprehensive network that encompasses herb-active components, pathways, lncRNAs, miRNAs, and targets. Expression levels of hypoxia-related lncRNAs in mononuclear cells isolated from peripheral blood of OP and normal patients were subsequently validated using quantitative real-time PCR (qRT-PCR). Protein levels of RUNX2 were determined through a western blot assay. RESULTS: CBFB, GLO1, NFKB2 and PIK3CA were identified as central therapeutic targets, and ADD3-AS1, DTX2P1-UPK3BP1-PMS2P11, TTTY1B, ZNNT1 and LINC00623 were identified as core lncRNAs. CONCLUSIONS: Our work uncovers a possible therapeutic mechanism for STZYD, providing a potential therapeutic target for OP. In addition, a prediction model of metabolism-related lncRNAs of OP progression was constructed to provide a reference for the diagnosis of OP patients.

A Retrospective Claims Database Study to Clarify Treatment Reality of Asthma Patients Before and After Referral to a Specialist.

Purpose: Japanese guidelines recommend that patients with uncontrolled asthma be referred by non-specialists to specialists (allergists and/or pulmonologists). This study investigated the reality of clinical practice in asthma patients referred to specialists in Japan. Patients and Methods: This was a retrospective, observational cohort study of asthma patients in a health insurance claim database (Cross Fact) referred from facilities with non-specialists to those with specialists from January 2016 to December 2018. The referred asthma patients were defined as patients with ≥4 inhaled corticosteroid (ICS)-containing prescriptions during a 1-year baseline period, with an asthma diagnosis, and who had visited a facility with specialists. Asthma exacerbation, maintenance treatment, laboratory tests, and medical procedures before and after referral were analyzed. Results: Data for 2135 patients were extracted, of which 420 with referral codes were analyzed. The proportion of patients with asthma exacerbations was 50.2% (95% confidence interval [CI]: 45.4-55.1%) before referral and 37.4% (95% CI: 32.7-42.2%) after, a significant decrease (P<0.001; McNemar test). The proportions of patients prescribed ICS alone, long-acting beta-agonists (LABA), and ICS/LABA were lower after referral than before, but the proportions of patients prescribed long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, and biologics increased after referral. More asthma-related laboratory tests were performed after referral, and spirometry incidence increased from 16.4% before referral to 51.4% after referral. Conclusion: This study shows a decrease in asthma exacerbations, change in asthma treatments, and increase in laboratory tests after referral to a specialist, suggesting that referrals to specialists lead to better management of asthma.

MicrobeTCM: A comprehensive platform for the interactions of microbiota and traditional Chinese medicine.

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com.

Machine Learning-based Models for Outpatient Prescription of Kampo Formulations: An Analysis of a Health Insurance Claims Database.

BACKGROUND: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations. METHODS: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated. RESULTS: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models. CONCLUSION: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Screening of potential phytomolecules against MurG as drug target in nosocomial pathogen Pseudomonas aeruginosa: perceptions from computational campaign.

The nosocomial infection outbreak caused by Pseudomonas aeruginosa remains a public health concern. Multi-drug resistant (MDR) strains of P. aeruginosa are rapidly spreading leading to a huge mortality rate because of the unavailability of promising antimicrobials. MurG glycotransferase [UDP-N-acetylglucosamine-N-acetylmuramyl (pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase] is located at the plasma membrane and plays a key role in murein (peptidoglycan) biosynthesis in bacteria. Since MurG is required for bacterial cell wall synthesis and is non-homologous to Homo sapiens; it can be a potential target for the antagonist to treat P. aeruginosa infection. The discovery of high-resolution crystal structure of P. aeruginosa MurG offers an opportunity for the computational identification of its prospective inhibitors. Therefore, in the present study, the crystal structure of MurG (PDB ID: 3S2U) from P. aeruginosa was selected, and computational docking analyses were performed to search for functional inhibitors of MurG. IMPPAT (Indian medicinal plants, phytochemicals and therapeutic) phytomolecule database was screened by computational methods with MurG catalytic site. Docking results identified Theobromine (-8.881 kcal/mol), demethoxycurcumin (-8.850 kcal/mol), 2-alpha-hydroxycostic acid (-8.791 kcal/mol), aurantiamide (-8.779 kcal/mol) and petasiphenol (-8.685 kcal/mol) as a potential inhibitor of the MurG activity. Further, theobromine and demethoxycurcumin were subjected to MDS (molecular dynamics simulation) and free energy (MM/GBSA) analysis to comprehend the physiological state and structural stability of MurG-phytomolecules complexes. The outcomes suggested that these two phytomolecules could act as most favorable natural hit compounds for impeding the enzymatic action of MurG in P. aeruginosa, and thus it needs further validation by both in vitro and in vivo analysis. HIGHLIGHTSThe top phytomolecules such as theobromine, demethoxycurcumin, 2-alpha-hydroxycostic acid, aurantiamide and petasiphenol displayed promising binding with MurG catalytic domain.MurG complexed with theobromine and demethoxycurcumin showed the best interaction and stable by MD simulation at 100 ns.The outcome of MurG binding phytomolecules has expanded the possibility of hit phytomolecules validation.Communicated by Ramaswamy H. Sarma.

Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan.

Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.

Prescription characteristics of Xue-Fu-Zhu-Yu-Tang in pain management: a population-based study using the National Health Insurance Research Database in Taiwan.

Objective: To explore the prevalence and distinctive features of Xue-Fu-Zhu-Yu-Tang (XFZYT) prescriptions by analyzing the National Health Insurance Research Database (NHIRD) to identify the specific medical problems for which XFZYT is prescribed. Methods: This nationwide, population-based, cross-sectional study included 109,073 XFZYT users and 532,848 XFZYT non-users among Chinese herbal product (CHP) users in NHIRD. Chi-squared tests were used to analyze disparities between the XFZYT user and XFZYT non-user cohorts, and the mean age was evaluated using the Wilcoxon rank-sum test. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: XFZYT was frequently used to treat pain. The top five conditions for which the Taiwanese traditional Chinese medicine (TCM) practitioners would prescribe XFZYT were chest pain; headache; myalgia and myositis; lumbago; and neuralgia, neuritis, and radiculitis. Conclusion: This study represents an inaugural comprehensive survey conducted on the utilization of XFZYT prescriptions among patients with diverse diseases. XFZYT is mostly used to treat pain conditions in Taiwan. Combined with the combination use of other CHPs, XFZYT is used to treat symptoms of the chest and respiratory system, soft tissue conditions, menstruation disorders, and joint and back discomfort. These results suggest that further clinical trials are warranted to verify the effects of XFZYT in pain management.