An integrative approach to uncover the components, mechanisms, and functions of traditional Chinese medicine prescriptions on male infertility.

Male infertility is a major and growing health problem with an estimated global prevalence of 4.2%. The current therapy is limited by the unknown etiology of MI, emphasizing the critical requirement forward to a more efficient method or medication. Through thousands of years, Traditional Chinese Medicine (TCM) has been shown to be effective in treating MI effectively. However, the components, mechanisms and functions of TCM prescriptions on MI are still obscure, severely limiting its clinical application. In order to discover the molecular mechanism of TCM against MI, our study presents a comprehensive approach integrated data mining, network pharmacology, molecular docking, UHPLC-Q-Orbitrap HRMS, and experimental validation. Here, we begin to acquire 289 clinical TCM prescriptions for MI from a TCM hospital's outpatient department. Then, Core Chinese Materia Medica (CCMM) was then retrieved from the TCM Inheritance Support System (TCMISS), which was utilized to discover the underlying rules and connections in clinical prescriptions. After that, 98 CCMM components and 816 MI targets were obtained from ten distinct databases. Additionally, the network pharmacology methods, including network construction, GO and KEGG pathway enrichment, PPI analysis, were utilized to reveal that kaempferol, quercetin, isorhamnetin, and beta-sitosterol are the core components of CCMM in treating MI. The mechanisms and functions of CCMM against MI are hormone regulation, anti-apoptosis, anti-oxidant stress, and anti-inflammatory. Furthermore, the strong connections between four core components and six key targets were verified using a molecular docking method. Following that, the core components of the CCMM extract were identified using UHPLC-Q-Orbitrap HRMS analysis. Finally, in vivo experiments demonstrated that CCMM and four core components could improve the density, motility, viability of sperm, lecithin corpuscle density, decrease the rate of sperm malformation and testis tissue damage, and regulate the protein expressions of AKT1, MAPK3/1, EGFR, and TNF-α in a mouse model of MI. UHPLC-Q-Orbitrap HRMS analysis and in vivo experiments further validated the results of data mining, network pharmacology, and molecular docking. Our study could uncover the components, mechanisms, and functions of TCM prescriptions against MI and develop a new integrative approach to demonstrate TCM's multi-component, multi-target, and multi-pathway approach to disease treatment.

An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the New Candidate Active Component and Mechanism of Cuscutae Semen-Mori Fructus Coupled-Herbs in Treating Oligoasthenozoospermia.

PURPOSE: One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), Cuscutae Semen-Mori Fructus coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive. METHODS: Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA. RESULTS: The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP. CONCLUSION: Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.

[Medication experience of TCM Master Academician Wang Qi in the treatment of premature ejaculation: Data mining and analysis].

Objective: To analyze the academic thought, medication experience and prescription rules of Academician Wang Qi in the treatment of premature ejaculation (PE) using the TCM inheritance support platform (V2.5). METHODS: We collected and sorted out the medical records on the treatment of PE from Academician Wang Qi's Clinic. We established a database of medical records on the TCM inheritance support platform, analyzed the drugs and prescriptions in the database and explored new prescriptions using "statistical reports" and "data analysis" systems on the platform. RESULTS: A total of 91 effective prescriptions were recorded, involving 148 TCM drugs, with Phellodendron, Amomum Villosum, Polygala Tenuifolia, Tuckahoe, Lodestone, Oyster, Acanthopanax Senticosus, Uncaria, Tribulus, and Keel as the top 10 with the highest frequency of use, which were featured mainly by "warm" and "cold" concerning the four natures, "sweet", "bitter" and "pungent" relating to the five flavors, and acting on "kidney meridian", "liver meridian" and "heart meridian" in terms of the meridian tropisms. In addition, 5 new prescriptions were obtained through unsupervised entropy hierarchical clustering. CONCLUSIONS: In the treatment of PE, Academician Wang Qi employs tranquilizing the mind and consolidating the kidney (An Zhi Gu Shen) as the primary strategy, taking into account the three organs of heart, liver and kidneys, focusing on the phase of calming the mind or regulating the liver or clearing the kidney or controlling fire, and adding or reducing drugs according to different conditions and syndromes, which conforms to his diagnosis and treatment mode of "body differentiation－disease differentiation－syndrome differentiation". The analysis of the potential new prescriptions also accords with Academician Wang Qi's rules of medication, which can provide some ideas for the clinical treatment of and scientific researches on premature ejaculation in the future.

[Academician Wang Qi's medication rules for oligoasthenozoospermia: An analysis based on the Traditional Chinese Medicine Inheritance Auxiliary Platform].

OBJECTIVE: To analyze the medication rules for oligoasthenozoospermia (OAZ) observed by Wang Qi, an academician, master of Traditional Chinese Medicine (TCM) and initiator of andrology in TCM. METHODS: We collected the outpatient cases of OAZ treated by Wang Qi and established a database of clinical medical records using the TCM Inheritance Auxiliary Platform. Employing the integrated rule-based system for analysis of the software, we modified the mutual information method, complex system entropy clustering analysis and other data mining methods, and summarized the medication rules Wang Qi followed in the treatment of OAZ. RESULTS: A total of 134 prescriptions made by Wang Qi for the treatment of OAZ were collected, involving 110 TCM drugs, which are mainly neutral and warm in nature and taste sweet and mostly act through the liver and kidney meridians. The core formula ingredients of the prescriptions included Morinda officinalis, Cuscuta chinensis, Lycium barbarum, Mulberry, Angelica sinensis, Astragalus mongholicus and Fish Maw, and most frequently Morinda officinalis, Cuscuta chinensis, Lycium barbarum and Mulberry. CONCLUSIONS: Wang Qi holds that kidney deficiency, dampness-heat, blood stasis and toxin are the main pathogenic factors for OAZ. The basic treatment of OAZ is to invigorate the kidney and replenish the essence, and meanwhile activate blood circulation, dissipate stasis and eliminate dampness-heat.

Predictors of caregiver burden in patients with neurologic Wilson disease.

OBJECTIVES: Caregiver burden in neurologic Wilson disease (NWD) has received little attention. We investigated predictors of caregiver burden in Chinese NWD patients. METHODS: Participants in this retrospective study were NWD patients admitted to The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from 1 August to 31 December 2019. Sociodemographic information was recorded for caregivers and NWD patients. Caregiver burden was evaluated using the Caregiver Burden Inventory (CBI). Cognitive impairment, functional problems, depression and anxiety were evaluated by professional interviewers. Path analysis was used to evaluate predictors of CBI scores. RESULTS: Sixty NWD patients were enrolled (mean age: 21.35 ± 4.89 years; mean NWD duration: 7.85 ± 3.11 years). The mean CBI score was 52.00 ± 17.16. Care duration had a significant direct effect on CBI score after controlling for confounders (r = 0.493). Cognitive impairment (r = -0.426), functional problems (r = 0.581), depression (r = 0.349) and anxiety (r = 0.317) had significant indirect effects on CBI score. CONCLUSION: Caregivers of NWD patients may experience a medium level of caregiver burden. NWD duration, cognitive impairment, functional problems, depression and anxiety in NWD patients may be useful predictors of caregiver burden.

[Study on HPLC fingerprint characteristics of Selaginella plants].

OBJECTIVE: To establish a method to analyze HPLC fingerprint characteristics of 10 plants from Selaginella. METHOD: HPLC was applied for establishment of fingerprints, which were used to evaluate and distinguish the different species of Selaginella. RESULT: The different species from Selaginella showed different HPLC fingerprint characteristic. The samples of the same species but collected in different period, different environment or different locations showed certain difference in fingerprints CONCLUSION: 2 important mutual fingerprint peaks were found in the 10 plants of Selaginella species and 5 peaks can be used as "main fingerprint peaks". The dates of these peaks can used for assessment of phylogenetic relation among species and evaluation of quality.