Mechanism of Preventing Recurrence of Stage II-III Colorectal Cancer Metastasis with Immuno-inflammatory and Hypoxic Microenvironment by a Four Ingredients Chinese Herbal Formula: A Bioinformatics and Network Pharmacology Analysis.

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

A Review of Traditional Chinese Medicine for Triple Negative Breast Cancer and the Pharmacological Mechanisms.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Conventional treatment options for TNBC often have limited efficacy and significant side effects. In recent years, traditional Chinese medicine (TCM) has shown promising results in the treatment of TNBC. TCMs include herb combinations that have synergistic effects to regulate homeostasis in the body, reduce tumor resistance, and improve patient quality of life. At present, three main TCM methods are used to treat TNBC in the clinic: strengthening the body's resistance, dispelling phlegm, and removing cancer toxins. This paper reviews the theories and mechanisms of each in TNBC treatment. The method of strengthening the body's resistance emphasizes enhancing the body's original Qi to fight against pathogenic factors; the method of dispelling phlegm seeks to eliminate phlegm stagnation and alleviate the burden on affected organs; the method of removing cancer toxins focuses on detoxification and detumescence to remove the toxic elements associated with TNBC. Although these methods treat TNBC from different etiologies, they have achieved good therapeutic effects and represent an important academic approach: That is, to cure the disease with a comprehensive view of the body and restore the balance of Yin and Yang. This knowledge lays a foundation for the future development and reasonable application of TCM in the clinic.

Exploring the Mechanisms of Yishen Tongluo Decoction on Repairing DNA Damage in Mouse Spermatogonia Cells Based on Whole Transcriptome Sequencing.

The aim of this study was to investigate the potential mechanism through which Yishen Tongluo decoction (YSTL) repairs DNA damage caused by benzo(a)pyrene diol epoxide (BPDE) in mouse spermatocytes (GC-2). The GC-2 cells were divided randomly into the control group, BPDE group, and low-, medium-, and high-dose YSTL groups of YSTL decoction. A comet assay was used to detect the DNA fragment index (DFI) of cells in each group. Based on the DFI results, whole transcriptome sequencing was conducted, followed by trend analysis, gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and ceRNA network analysis. Compared with the control group, the BPDE group reported a significant increase in the DNA fragmentation index (DFI) (p < .05). Compared with the BPDE group, the low-, high- and medium-dose YSTL groups had a significantly reduced DFI (p < .05). Whole-transcriptome sequencing revealed seven differentially expressed circRNAs, 203 differentially expressed miRNAs, and 3,662 differentially expressed mRNAs between the control group and the BPDE group. There was a total of 12 differentially expressed circRNAs, 204 miRNAs, and 2150 mRNAs between the BPDE group and the traditional Chinese medicine group. The pathways involved include DNA repair pathway, nucleotide excision repair pathway, base excision repair pathway, etc. The ceRNA network reported that Hmga2 was the core protein involved, novel_cir_000117 and mmu-miR-466c-3p were located upstream of Hmga2, and they were regulatory factors associated with Hmga2. Finally, we conclude that YSTL decoction may repair sperm DNA damage caused by BPDE through the novel_cir_000117-mmu-miR-466c-3p-Hmga2 pathway.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Exploration of Potential Targets and Molecular Mechanisms of the Yiqi Jianpi Tongqiao Formula in Treating Allergic Rhinitis Mouse Model based on Network Pharmacology and Molecular Docking.

OBJECTIVE: To investigate the therapeutic effect of Yiqi Jianpi Tongqiao (YJT) formula (Hedysarum Multijugum Maxim, Magnoliae Flos, Xanthii Fructus, Notopterygii Rhizoma Et Radix, Kaempferiae Rhizoma, Acoritataninowii Rhizoma, Saposhnikoviae Radix) on an allergic rhinitis mouse model, and to explore the active ingredients, key targets, and molecular mechanisms of this formula using network pharmacology and molecular docking methods. METHODS: An allergic rhinitis mouse model was established to observe changes in rhinitis symptoms, nasal mucosal morphology, and serum indicators after administering the YJT formula. The TCMSP, GeneCards, OMIM, and DisGeNET databases were used to screen for the active ingredients, action targets, and disease targets of the YJT formula. The Cytoscape software was used to construct a network of the active ingredients and action targets. The protein-protein interaction (PPI) network was used to predict hub genes. The corresponding active compounds with the hub genes' highest oral bioavailability (OB) values were identified, followed by molecular docking analysis. RESULTS: Animal experiments demonstrated that the YJT formula reduced rhinitis symptoms (nasal itching, runny nose, and face scratching) in allergic rhinitis mice, as well as decreased nasal mucosal inflammatory reactions and serum inflammatory indicators (histamine, OVAspecific IgE, IL-1ß levels). Furthermore, 63 active components and 101 potential indicator targets of the YJT formula were identified, along with 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2), and the corresponding active compounds with the highest OB values were quercetin, aloe-emodin, and denudanolide b. Molecular docking results revealed the binding energy between quercetin, aloe-emodin, denudanolide b and 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2) were -5.78 to -10.22 kcal/mol, the binding energy between dexamethasone and 5 hub genes were -6.3 to -9.7 kcal/mol. In addition, GO and KEGG analysis suggested significant enrichment of these genes in biological processes such as response to lipopolysaccharide, response to molecule of bacterial origin, and response to reactive oxygen species, as well as signaling pathways like AGE-RAGE signaling pathway in diabetic complications, Lipid and atherosclerosis, and IL-17 signaling pathway. CONCLUSION: The YJT formula has therapeutic effects in an allergic rhinitis mouse model, with the main active components being quercetin, aloe-emodin, and denudanolide b, and the key targets being IL6, AKT1, IL1B, VEGFA, and PTGS2, involving multiple signaling pathways.

SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment.

Objective: Diabetic retinopathy (DR) is a severe diabetic complication that leads to severe visual impairment or blindness. He-Ying-Qing-Re formula (HF), a traditional Chinese medicinal concoction, has been identified as an efficient therapy for DR with retinal vascular dysfunction for decades and has been experimentally reported to ameliorate retinal conditions in diabetic mice. This study endeavors to explore the therapeutic potential of HF with key ingredients in DR and its underlying novel mechanisms. Methods: Co-expression gene modules and hub genes were calculated by weighted gene co-expression network analysis (WGCNA) based on transcriptome sequencing data from high-glucose-treated adult retinal pigment epithelial cell line-19 (ARPE-19). The chromatographic fingerprint of HF was established by ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-Q-TOF-MS). The molecular affinity of the herbal compound was measured by molecular docking. Reactive oxygen species (ROS) was measured by a DCFDA/H2DCFDA assay. Apoptosis was detected using the TUNEL Assay Kit, while ELISA, Western blot, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used for detecting the cytokine, protein, and mRNA expressions, respectively. Results: Key compounds in HF were identified as luteolin, paeoniflorin, and nobiletin. For WGCNA, ME-salmon ("protein deacetylation") was negatively correlated with ME-purple ("oxidative impairment") in high-glucose-treated ARPE-19. Luteolin has a high affinity for SIRT1 and P53, as indicated by molecular docking. Luteolin has a hypoglycemic effect on type I diabetic mice. Moreover, HF and luteolin suppress oxidative stress production (ROS and MDA), inflammatory factor expression (IL-6, TNF-α, IL1-ß, and MCP-1), and apoptosis, as shown in the in vivo and in vitro experiments. Concurrently, treatment with HF and luteolin led to an upregulation of SIRT1 and a corresponding downregulation of P53. Conclusion: Using HF and its active compound luteolin as therapeutic agents offers a promising approach to diabetic retinopathy treatment. It primarily suppressed protein acetylation and oxidative stress via the SIRT1/P53 pathway in retinal pigment epithelial cells.

Sijunzi decoction, a classical Chinese herbal formula, improves fatigue symptoms with changes in gut microbiota in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial. METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. CONCLUSION: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. CLINICAL TRIAL REGISTRATION: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).

Dietary Chinese herbal formula supplementation improves yolk fatty acid profile in aged laying hens.

Chinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p < .05) the concentrations of several saturated fatty acids (SFA, including myristic acid and stearic acid), monounsaturated fatty acids (MUFA, including petroselinic acid, elaidic acid, trans-11-eicosenoic acid, and cis-11-eicosenoic acid), polyunsaturated fatty acids (PUFA, including linolelaidic acid, linoleic acid, γ-linolenic acid, α-linolenic acid, 11c,14c-eicosadienoic acid, eicosatrienoic acid, homo-γ-linolenic acid, arachidonic acid, and docosapentaenoic acid), and fatty acid indexes (total MUFA, n-3 and n-6 PUFA, PUFA/SFA, hypocholesterolemic/hypercholesterolaemic ratio, health promotion index, and desirable fatty acids) in egg yolks. Collectively, these findings suggest that dietary CHF supplementation could improve the nutritional value of fatty acids in egg yolks of aged laying hens, which would be beneficial for the production of healthier eggs to meet consumer demands.

Efficacy of Chinese Herbal Medicine Formula in the Treatment of Mild to Moderate Erectile Dysfunction: Study Protocol for a Multi-Center, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Introduction: Erectile dysfunction (ED) is a prevalent condition in urology, primarily managed with PDE5 inhibitors (PDE5Is). However, approximately 20% of patients do not experience improvement in overall sexual satisfaction (OS) after taking PDE5Is. Among these, traditional Chinese medicine (TCM) has emerged as a complementary approach, with formulas like Hongjing I granules (HJIG) showing promise in preliminary studies. This study aims to rigorously evaluate the effectiveness and safety of HJIG in mild to moderate ED cases, assessing improvement in both sexual function and TCM pattern alignment. Methods: This study is a randomized, double-blind, placebo-controlled multicentre trial. Recruitment will be conducted from patients who have a strong willingness to try using only traditional Chinese medicine treatment (This is very common in traditional Chinese medicine hospitals.). A total of 100 patients diagnosed with mild to moderate ED caused by qi deficiency and blood stasis will be recruited and randomly assigned to receive one of two treatments: HJIG (N = 50) or placebo (N = 50). Patients will receive 8 weeks of treatment and a 16-week follow-up starting from the fourth week of treatment. Outcome measures, including the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, Sexual Encounter Profile (SEP), and Traditional Chinese Medicine symptom score, will be evaluated. Discussion: The expected outcome of this trial is that the use of the herbal formula HIJG alone can improve overall sexual satisfaction (OS) in patients with mild to moderate ED, while also improving their traditional Chinese medicine symptom scores. This will provide evidence-based support for the use of Chinese medicine in the treatment of ED in China. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000041127, Registered on 19 December 2020, https://www.chictr.org.cn/showproj.html?proj=46469. Trial Status: Recruitment began in March 2021, therefore 80 patients have been recruited. It is expected to finish recruiting in December 2023.

Effectiveness and safety of Xuefu Zhuyu oral liquid on -stagnation and blood-stasis pattern in patients with stable angina, tension-type headache and primary dysmenorrhea: rationale and design of a master protocol.

We present the rationale and design of a master protocol study that clarifies the effectiveness and safety of Chinese herbal formulas on -stagnation and blood-stasis pattern (QBP). Three randomized controlled trials (RCTs) and real-world observational studies. Based on three registry cohorts of stable angina, tension-type headache and primary dysmenorrhea, patients with QBP will be enrolled in RCTs to receive either Xuefu Zhuyu (, XFZY) oral liquid or a placebo, while patients with non-QBP will be enrolled in the observational studies and experience follow-up. 1414 patients (RCTs: 574; observational studies: 840) will be recruited at seven centers in China over a 3-year period. The primary outcome is the visual analog scale of pain intensity. Adverse events will also be reported. The analysis will be undertaken separately in each sub-study, and then an overall analysis combining multiple subgroups will be performed to comprehensively investigate the effect of XFZY oral liquid. This study will provide high-quality evidence of XFZY oral liquid for QBP patients and show a paradigm of post-marketing evaluation of the effectiveness and safety for Chinese medicine following the notion of the pattern dominating different disease research models.

Based on mRNA Sequencing Techniques to Explore the Molecular Mechanism of Buzhong Yiqi Decoction for Autoimmune Thyroiditis.

OBJECTIVE: Autoimmune diseases (AD) account for a high percentage of the population. One of the most prevalent is autoimmune thyroiditis (AIT). However, the therapeutic effects of Buzhong Yiqi (BZYQ) decoction on AIT have not been studied yet. The majority of the present study was conducted on NOD.H-2h4 mice in an attempt to ascertain the therapeutic effects of BZYQ decoction on AIT. METHODS: The 0.05% sodium iodide water (NaI)-induced AIT mice model was established. A total of nine NOD.H-2h4 mice were randomly divided into three groups: the normal group provided with regular water, the model group drinking freely 0.05% NaI, and the treatment group treated with BZYQ decoction (9.56 g/kg) after NaI supplementation (NaI + BZYQ). BZYQ decoction was administered orally once daily for eight weeks. The thyroid histopathology test was used to measure the severity of lymphocytic infiltration. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of anti-thyroglobulin antibody (TgAb), interleukin (IL)-1ß, IL-6, and IL-17. The Illumina HiSeq X sequencing platform was utilized to analyze the thyroid tissue by mRNA expression profiles. Bioinformatics analysis was used to investigate the biological function of the differentially expressed mRNAs. In addition, the expression of Carbonyl Reductase 1 (CBR1), 6-Pyruvoyltetrahydropterin Synthase (PTS), Major Histocompatibility Complex, Class II (H2-EB1), Interleukin 23 Subunit Alpha (IL-23A), Interleukin 6 Receptor (IL-6RA), and Janus Kinase 1 (JAK1) was measured by quantitative real-time PCR (qRT-PCR). RESULTS: The treatment group exhibited significantly lower rates of thyroiditis and lymphocyte infiltration compared to the model group. Serum levels of TgAb, IL-1ß, IL-6, and IL-17 were significantly higher in the model group, but they fell dramatically after BZYQ decoction administration. According to our results, 495 genes showed differential expression in the model group compared to the control group. Six hundred twenty-five genes were significantly deregulated in the treatment group compared to the model group. Bioinformatic analysis showed that most mRNAs were associated with immune-inflammatory responses and were involved in multiple signaling pathways, including folate biosynthesis and the Th17 cell differentiation pathway. CBR1, PTS, H2-EB1, IL23A, IL-6RA and JAK1 mRNA participated in folate biosynthesis and the Th17 cell differentiation pathway. The qRT-PCR analysis confirmed that the above mRNAs were regulated in the model group compared to the treatment group Conclusion: The results of this investigation have revealed novel insights into the molecular mechanism of action of BZYQ decoction against AIT. The mechanism may be partially attributed to the regulation of mRNA expression and pathways.

The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis.

To assess and analyse the effectiveness and safety of combined Chinese herbal formula (CHF) and metformin treatment in the modulation of the gut microbiota in the amelioration of type 2 diabetes mellitus(T2DM), all publications addressing the effect of this combination treatment on the quantitative alterations in the gut microbiota and glucose parameters were collected. Rob tool in the Cochrane handbook was performed to evaluate the methodological quality of all included studies. Relevant information and statistics were abstracted and synthesized in Review Manager 5.4 to evaluate the efficacy of combination treatment. Sensitivity analyses and subgroup analyses were used to analyse the sources of heterogeneity. Publication bias analyses were performed by Stata software to assess the robustness and quality of the outcomes. As a result, a total of 12 eligible RCTs with 1307 T2DM participants from 7 electronic databases were included. Combined CHF with metformin treatment showed better efficacies than metformin monotherapy in regulating the structure of the gut microbiota, characterized by increased Bifidobacterium, Lactobacillus and Bacteroidetes and decreased Enterobacteriaceae, Enterococcus, and Saccharomyces along with better decreases in glycated haemoglobin, fasting plasma glucose, 2-hour postprandial blood glucose, fasting insulin and homeostasis model assessment of insulin resistance. Subgroup analyses further analysed the effect of metformin doses and CHF classifications on controlling hyperglycaemia and altering the gut microbiota. In conclusion, our meta-analysis suggested that combined CHF with metformin treatment is promising for the modulation of the gut microbiota along with ameliorating hyperglycemia in T2DM patients. Importantly, more well-designed RCTs are needed to validate the outcomes and verify the treatment value for clinical purposes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291524, identifier CRD42021291524.

Influence of Chinese Herbal Formula on Bone Characteristics of Cobb Broiler Chickens.

To evaluate the prevention and treatment effect of a Chinese herbal formula (CHF) on the bone disease of Cobb broiler chickens, compare its efficacy with Bisphosphonates (BPs), and provide a theoretical basis for studying the nutritional regulation technology of CHF to improve the bone characteristics of broiler chickens. In this study, 560 one-day-old Cobb broiler chickens were examined for the influence of Chinese herbal formula (CHF) and Bisphosphonates (BPs). Different doses of CHF and BPs were added to the diet, and the 30- and 60-day-old live weight, tibial bone strength, the microstructure of the distal femur cancellous bone, blood biochemical indexes related to bone metabolism, and genes related to bone metabolism were determined and analyzed. The results showed that the live weight of Cobb broilers fed with CHF and BPs in the diet was as follows: The live weight of the CHF group was higher than that of the normal control (NC) group, while the live weight of the BPs group was lower than that of the NC group; the CHF and BPs improved the bone strength of Cobb broilers and increased the elastic modulus, yield strength, and maximum stress of the tibia. CHF and BPs increased the cancellous bone mineral density (BMD), bone tissue ratio (BV/TV), bone surface area tissue volume ratio (BS/TV), bone trabecular thickness (Tb.Th), and bone trabecular number (Tb.N) in the distal femur, and decreased the bone surface area bone volume ratio (BS/BV) and bone trabecular separation (Tb.Sp). Thus, the microstructure of the bone tissue of the distal femur was improved to a certain extent. Both the CHF and the BPs also increased the serum levels of the vitamin D receptor (VDR), osteoprotegerin (OPG), and alkaline phosphatase (ALP), and decreased the content of osteocalcin (OT). Meanwhile, CHF and BPs upregulated the expression of osteogenic genes (BMP-2, OPG, Runx-2) to promote bone formation and downregulated the expression of osteoclastic genes (RANK, RANKL, TNF-α) to inhibit bone resorption, thus affecting bone metabolism. Conclusion: The CHF could improve the skeletal characteristics of Cobb broilers by upregulating the expression of bone-forming-related genes and downregulating the expression of bone-breaking-related genes, thus preventing and controlling skeletal diseases in Cobb broilers. Its effect was comparable to that of BPs. Meanwhile, the CHF-H group achieved the best results in promoting the growth and improvement of the skeletal characteristics of Cobb broilers based on the live weight and skeletal-characteristics-related indexes.

Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms.

BACKGROUND: Chronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear. AIM: To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG. METHODS: We systematically searched 3 English (PubMed, Embase, Medline) and 4 Chinese databases (Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG. RESULTS: Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that: (1) SLBZS was superior to conventional therapies [risk ratio (RR): 1.29, 95% confidence interval (CI): 1.21 to 1.37, P < 0.00001]; (2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval (95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity (RR: 1.20, 95%CI: 1.11 to 1.30, P < 0.00001); and (3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others. CONCLUSION: SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.

Transcriptomics and proteomics analysis to explore the mechanism of Yishen Tongluo formula repairing sperm DNA damage in rats.

The sperm DNA fragmentation index (DFI) is an objective indicator of male fertility. Currently, effective treatments for high sperm DFI are limited and traditional Chinese medicine (TCM) has certain advantages in this aspect. Yishen Tongluo formula (YSTL), a TCM formula, has been found to reduce DFI in patients. To better understand the mechanisms underlying its activity, we used transcriptomics and proteomics to analyse the potential target gene YSTL repairing tripterygium glycosides (TGs)-mediated sperm DNA damage in rats, followed by validation analyses using RT-qPCR and western blotting, which showed that relative to the control group, DFI was markedly elevated in the TGs group, but markedly lower in the YSTL group relative to the TGs group. KEGG pathway analysis of 119 differentially expressed genes and 158 DEPs identified using trend analysis revealed that they were enriched for apoptosis and base excision repair at the transcriptomic level and for microRNAs in cancer and complement and coagulation cascades at the proteomic level. Ttr and Pnpla2 were identified as potential target genes for YSTL. Our data show that YSTL can protect rat sperm DNA from TGs-induced damage, which may be related to apoptosis, DNA repair and other pathways, and the possible target genes are Ttr and Pnpla2.

Systematic review and meta-analysis of Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: Evidence for clinical practice and future trials.

Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly decreases the quality of life of patients and their families, and affects patients' mental health. No specific western medications are available. Ancient classical Chinese medical texts have recognized Tongxie Yaofang (TXYF) as a therapy for diarrhea which is widely used in clinical practice. Standard TXYF prescription (S-TXYF) is composed of four herbal medicines: Atractylodes macrocephala Koidz. [Asteraceae; Rhizoma Atractylodis Macrocephalae.], Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba], Citrus × aurantium L. [Rutaceae; Citri Reticulatae Pericarpium] and Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk. [Umbelliferae; Saposhnikoviae Radix]. This review aimed to evaluate the therapeutic effects and safety of S-TXYF for IBS-D. Methods: Eight English and Chinese electronic databases were searched from their inception to 25 December 2021 for randomized controlled trials (RCTs) comparing S-TXYF with placebo, western medications or no treatment for IBS-D. The primary outcome was the global improvement of IBS-D symptoms. Data were analyzed using Cochrane's Revman 5.4 software. Evidence certainty was assessed using the online GRADEpro tool for the primary outcome. Results: Eleven RCTs involving 985 adults with IBS-D were included. For global improvement of symptoms, S-TXYF was superior to western medication and placebo (moderate evidence by GRADE). Regarding the improvement of stool consistency, stool frequency and abdominal pain, S-TXYF was significantly effective than placebo. In addition, S-TXYF was superior to western medication on improving the quality of life and relieving anxiety. Six trials reported adverse events: five of them reported (non-serious) adverse events occurred in both groups, and one trial reported that 3 cases with adverse events (constipation, elevation in liver-enzyme, nausea) occurred in S-TXYF group and 3 cases with adverse events (abdominal distension, nausea) occurred in placebo group. Conclusion: Although current results showed that S-TXYF may have potential to treat IBS-D and its use appears to be safe, no a clear and confirmed conclusion can be drawn from our review as the overall inadequate design of the included trials reviewed. So more rigorous trials are warranted to establish confirmed evidence on its benefits and safety.

Evidence construction of Chinese herbal formulae for the treatment of H. pylori positive peptic ulcer: A Bayesian network Meta-analysis.

PURPOSE: Helicobacter pylori (H. pylori) positive peptic ulcer disease (PUD) is a highly prevalent digestive disease with serious consequences of poor prognosis without rational medical intervention. Apparent advantages of Chinese herbal formulae application in PUDs have been appreciated by clinical practitioners recently in China. However, there is no enough viewpoint of evidence-based medicine for them to reach a broad consensus at the more favorable formulae. Therefore, we adopted the method of Bayesian network Meta-analysis (BNMA) in order to get a solution. METHOD: Literature retrieval of clinical randomized controlled trials (RCTs) was conducted with eight databases of PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, the VIP medicine information system, the Wanfang Data Knowledge Service Platform and Chinese Biomedical Literature Service System. Review Manager 5.4 software, R project 4.1.1 software and STATA16.0 software were used to carry out this BNMA. The primary outcome indicator is H. pylori eradicated rate. The secondary outcome indicator is clinical effectiveness rate, recurrence rate and adverse reaction report. RESULT: A total of fifty-one RCTs involving 5172 patients and ten therapeutic strategies were included in this BNMA. The results showed that supplementation with Chinese herbal formulae significantly improved the eradication rate, clinical efficiency and reduced recurrence rate of H. pylori compared with the single conventional triple therapy (CON) group in a relatively safe manner. Comprehensive therapeutic efficacy analysis of H. pylori eradicated rate and clinical effectiveness rate showed that CON combined with Xiangsha Liujunzi decoction (XSD) manifests at the first grade among these ten therapeutic strategies. CONCLUSION: The efficacy and safety of Chinese herbal formulae and conventional triple therapy were validated by this BNMA. CON+XSD appears to be the most satisfactory therapeutic strategy for H. pylori-positive PUD, reminding clinicians of the potential value of the combination of Chinese herbal formulae and conventional chemotherapy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021268574.

Integrative analysis of network pharmacology and proteomics to identify key targets of Tuomin-Zhiti-Decoction for allergic rhinitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic rhinitis (AR) is one of most prevalent disease and it is urgent need to develop new drug. Tuomin-Zhiti-Decoction (TZD) is a traditional medicinal compound consisting of eleven different herbs and has a significant effect on AR, yet its underlying mechanism is still unknown. AIM OF THE STUDY: The aim of this study was to confirm the anti-AR effects and the underlying mechanism of TZD. Integrative analysis of network pharmacology and proteomics to explore the common mechanism of TZD treating AR. MATERIALS AND METHODS: Mice were subjected to serial intranasal challenge with ovalbumin (OVA), we examinaed the nasal symptoms, histopathology and Th1/Th2-related cytokines after TZD treatments. Active compounds, potential targets and underlying mechanisms of TZD against AR were systematically clarified by integrating network pharmacology and proteomics analysis. Then we validated the binding affinity between the key potential targets and matching active compounds using molecular docking evaluation. RESULTS: TZD controlled allergy by reduction of OVA-specific immunoglobulin E (IgE) and histamine release. In nasal tissue, TZD decreased nasal rubbing, sneezing and reduced AR-induced damage to nasal mucosa, accordingly, the nasal symptoms were also clearly ameliorated. Moreover, TZD modulated the balance of Th1/Th2/Th17. The proteomics analysis recognized 41 differentially expressed proteins (DEPs). Integrative analysis of network pharmacology and proteomics, we found IL-6 and CD40 could be potential protein targets of TZD against AR, quercetin and wogonin may play more effective roles in AR. Active core compounds of TZD could bind closely to the key targets by molecular docking. CONCLUSION: TZD may have therapeutic potential for treating AR, integrating analysis of network pharmacology and proteomics uncovered the underlying mechanism and targets of TZD, which provides a scientific method for the sensible development of traditional Chinese medicine.

Randomized double-blind trial comparing low dose and conventional dose of a modified traditional herbal formula Guizhi Fuling Wan in women with symptomatic uterine fibroids.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Guizhi Fuling Wan is one common remedy for treating uterine fibroids (UFs) and the relevant symptoms in Traditional Chinese Medicine (TCM). Previous systematic reviews showed that Guizhi Fuling Formula appeared to have additional benefit based on mifepristone treatment in reducing volume of fibroids. AIM OF STUDY: To study the efficacy and safety of the conventional dose of a modified herbal formula Guizhi Fuling Wan in patients with symptomatic uterine fibroids in comparison with a sub-effective dose control. MATERIALS AND METHODS: This randomized double-blind, dosage-controlled trial was carried out in an outpatient clinic of traditional Chinese medicine in Hong Kong. Women with symptomatic uterine fibroids diagnosed according to the WHO International Classification of Diseases (ICD-10) were recruited and randomly assigned to one of two groups that received modified Guizhi Fuling Wan at either a low dose or the conventional dose on a daily basis for 16 weeks. This study was quality controlled by a data safety monitoring board. The primary outcome was the symptom severity as measured with the Uterine Fibroid Symptom-Quality of Life questionnaire. The secondary outcomes included quality of life, menstrual bleeding (measured on a pictorial blood loss assessment chart), pain severity (measured on the 6-point behavioral rating scale), change in Chinese medicine syndrome score, fibroid volume (measured by magnetic resonance imaging), hemoglobin level, and hormone levels. RESULTS: Seventy-eight women were recruited for this study. Between-groups comparison showed no significant difference at the endpoint for all outcomes except for the Chinese medicine syndrome score; however, at the endpoint, within-group comparison showed significant improvement in both groups relative to baseline in symptom severity, functional influence of pelvic pain, Chinese medicine syndrome score, and fibroid volume and uterus condition on magnetic resonance imaging (p < 0.05).The low-dose group yielded greater endpoint improvement in the Chinese medicine syndrome score than the conventional-dose group (p=0.024). No serious adverse events related to the intervention were noted. CONCLUSION: Both low-dose and conventional-dose preparations significantly ameliorated uterine fibroid-related symptoms and fibroid volume, although no significant difference was found between the low-dose and conventional-dose groups. The herbal formula GuizhiFuling Wan is safe in women with uterine fibroids.

Comparative efficacy and safety of four classical prescriptions for clearing damp-heat recommended by clinical guidelines in treating rheumatoid arthritis: a network meta-analysis.

BACKGROUND: In China, along with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), some herbal formulae for clearing damp-heat are widely applied in treating rheumatoid arthritis (RA). We aimed to summarize and compare the clinical effects of 4 guideline-recommended formulae, including Baihuguizhi decoction, Dangguiniantong decoction, Simiao pill, and Xuanbi decoction. METHODS: PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technique Journals (CQVIP), WanFang, and SinoMed (CBM) databases were searched for randomized controlled trials from inception to July 2020 evaluating the efficacy and safety of these recommended herbal formulae combined with 1 csDMARD versus csDMARD alone in RA patients. A pairwise meta-analysis was conducted in RevMan 5.3 software, and a Bayesian network meta-analysis (NMA) was performed with Stata 14.0, R 4.0.2, GeMTC 0.14.3, and JAGS 4.3.0 software. Cochrane Handbook 5.1.0 was used to assess the risk of bias. Publication bias was evaluated using Egger's test, the trim-fill adjustment, and funnel plots. Trial sequential analysis (TSA) was performed to validate the overall results. The rank probability of interventions was calculated and clustered by the surface under the cumulative ranking curve (SUCRA). Pharmacologic actions of formulae were explored through the network pharmacology approach. RESULTS: A total of 15 studies, including 1,079 individuals, were identified. Simiao pill + csDMARD [SMPPD, odds ratio (OR) =6.62, 95% confidence interval (CI): 2.88 to 16.84] was superior to csDMARDs alone in clinical efficiency, and was more able to reduce C-reactive protein and erythrocyte sedimentation rate levels [mean difference (MD) =-7.91, 95% CI: -17.41 to -1.25; MD =-9.31, 95% CI: -14.48 to -5.56 respectively]. Although publication bias was observed (P=0.033), the trim-fill method indicated that the pooled values kept stable. Fewer adverse events (AEs) were shown with SMPPD (6.45%). TSA confirmed the results of efficacy rate at SMPPD. Network pharmacology included 5 common components and 66 common targets among 4 formulae in treating RA, involving regulating immunity and relieving inflammation. DISCUSSION: SMPPD might be a preferable complementary therapy for RA. However, considering the limitations of this study, recommendations for clinical practice should be validated by the results of further well-designed studies.