Clinical remission of moderate generalized myasthenia gravis through exclusive use of Buzhong Yiqi decoction: A case report.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder with significant morbidity and mortality. Traditional Chinese medicine (TCM) offers an alternative approach to standard pharmacological and surgical interventions, which are often associated with adverse side effects. This case report details the clinical remission of a 50-year-old male with moderate generalized MG following exclusive treatment with a modified Buzhong Yiqi decoction (BYD), a TCM formula, without the use of immunosuppressive agents. CASE SUMMARY: The patient presented with diplopia, bilateral ptosis, weakness in chewing, limb weakness, and other symptoms indicative of spleen and stomach qi deficiency. Modified BYD was prescribed, focusing on strengthening the spleen, nourishing qi and blood, and enhancing immune response. The treatment included ingredients such as Radix Astragali, Angelica sinensis, Atractylodes macrocephala, and others, aiming to restore balance and improve the patient's condition. After two weeks of TCM treatment, the patient showed significant improvement in symptoms of myasthenia. By the second month, all clinical symptoms had disappeared. The patient continued to receive the TCM regimen until the thirtieth month of treatment. At the time of writing this report, the patient has no clinical symptoms and has experienced no relapse. Notably, no obvious adverse effects were reported throughout the treatment. CONCLUSION: The success of this case suggests that TCM may serve as an independent treatment option for moderate MG, offering a steroid-free alternative, which would be particularly valuable for patients who are intolerant of or refuse steroid therapy, potentially with significant clinical implications. However it needs a randomized clinical trial comparing TCM to conventional Western medicine treatment to validate it.

Bu zhong Yiqi Decoction ameliorates mild cognitive impairment by improving mitochondrial oxidative stress damage via the SIRT3/MnSOD/OGG1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.

[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Integrating network pharmacology and experimental verification to investigate the pharmacological mechanisms of Buzhong Yiqi decoction in the treatment of non-small cell lung cancer.

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.

Jiawei Buzhong Yiqi decoction ameliorates polycystic ovary syndrome via oocyte-granulosa cell communication.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be effective in treating polycystic ovary syndrome (PCOS) in both clinical studies and practical practice, with the pharmacological mechanism remaining unknown. AIM OF THE STUDY: To explore the potential therapeutic effects and mechanistic insights of JWBZYQ in PCOS. MATERIALS AND METHODS: An overweight PCOS rat model was established via testosterone propionate (TP) injection and 45% high-fat diet (HFD). Then they were categorized into five distinct groups: Control group, Model group, low-dose of JWBZYQ (JWBZYQ1) group, high-dose of JWBZYQ (JWBZYQ2) group, and metformin (Met) group. Body weight, estrous cycle, and sex hormone levels were observed. Hematoxylin-Eosin staining was employed to investigate the histological characteristics of the ovaries. To identify the pathways that changed significantly, transcriptome analysis was performed. The protein and mRNA levels of key molecules in ovarian zona pellucida (ZP) organization, transzonal projections (TZPs) assembly, steroid hormone receptors, and steroidogenesis were assessed using phalloidin staining, immunohistochemistry, Western blot, and polymerase chain reaction. RESULTS: RNA-seq analysis demonstrated that regulation of hormone secretion, cilium assembly, cell projection assembly, and ZP production may all have crucial impact on the etiology of PCOS and therapeutic effect of JWBZYQ. In particular, PCOS rats exhibited elevated expressions of ZP1-3, which can be reversed by JWBZYQ2 particularly. Simultaneously, TZPs assembly was totally disrupted in PCOS rats, evidenced by the phalloidin staining, upregulated calcium-/calmodulin-dependent protein kinase II beta (CaMKIIß), and deficient p-CaMKIIß, myosin X (MYO10), proline-rich tyrosine kinase 2 (PTK2), and Fascin. Nonetheless, JWBZYQ or metformin treatment revived the disturbance, repairing the oocyte-granulosa cell communication, regulating steroidogenesis in PCOS rats. In this way, JWBZYQ and metformin exerted remarkable effects in alleviating altered ovarian morphology and function in PCOS rats, with JWBZYQ2 revealing the best effect. CONCLUSIONS: JWBZYQ restored the altered ovarian morphology and function by regulating the oocyte-granulosa cell communication, which was related with ZP organization and TZPs assembly in the ovary.

Clinical efficacy of Buzhong Yiqi decoction in the treatment of hospital-acquired pneumonia with multi-drug resistant bacteria: a prospective, randomized, multicenter controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Buzhong Yiqi decoction (, BZYQ) in the treatment of hospital-acquired pneumonia (HAP) with multi-drug-resistant bacteria (MDRB). METHODS: This 28-day study was conducted at 5 clinical centers in Shanghai. The eligible patients were randomly assigned (1:1) into the intervention group (BZYQ plus conventional Western Medicine therapy) and control group (conventional Western Medicine therapy). The primary outcomes were the clinical response, clinical pulmonary infection score (CPIS), and microbiologic response. The secondary outcomes were the 28-day all-cause mortality (ACM), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, ventilator weaning rate, length of mechanical ventilation (MV), length of hospital stay, and changes of infection indicators. RESULTS: Altogether 83 subjects in the intervention group and 85 subjects in the control group were analyzed. The clinical success rate (48.2%) and the pathogen eradication rate (59.0%) of the intervention group were all better than those of the control group (32.9% and 38.9%, respectively) with statistically significant differences (<0.05). The CPIS score of the intervention group (8.9 ± 1.7) was lower than that of the control group (9.6 ± 2.5) (<0.05). The length of MV in the intervention group [(13.7 ± 6.4) d] was significantly shorter than that of the control group [ (17.2 ± 7.2) d] (<0.05). The 28-day ACM of the intervention group (13.33%) was lower than that of the control group (21.2%) with no statistically significant difference (>0.05). The differences between two groups in ventilator weaning rate, length of hospital stay, and APACHE Ⅱ score were not statistically significant (> 0.05). The intervention group displayed decreases in white blood cell count, C-reactive protein, neutrophil percentage, and procalcitonin at day 28 compared with baseline (<0.05). No serious adverse events occurred in either group during the 28-day follow-up. CONCLUSION: BZYQ may be an effective therapeutic option for the management of HAP with MDRB.

Combined Treatment with Bojungikgi-tang (Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells.

OBJECTIVE: To examine the effect of combined treatment with Bojungikgi-tang (BJIGT, Buzhong Yiqi Decoction) and riluzole (RZ) in transactive response DNA-binding protein 43 (TDP-43) stress granule (SG) cells, a amyotrophic lateral sclerosis (ALS) cell line using transcriptomic and molecular techniques. METHODS: TDP-43 SG cells were pretreated with BJIGT (100 µg/mL), RZ (50 µmol/L), and combined BJIGT (100 µg/mL)/RZ (50 µmol/L) for 6 h before treatment with lipopolysaccharide (LPS, 200 µmol/L). Cell viability assay was performed to elucidate cell toxicity in TDP-43 SC cells using a cell-counting kit-8 (CCK8) assay kit. The expression levels of cell death-related proteins, including Bax, caspase 1, cleaved caspase 3 and DJ1 in TDP-43 SG cells were examined by Western blot analysis. The autophagy-related proteins, including pmTOR/mTOR, LC3b, P62, ATG7 and Bcl-2-associated athanogene 3 (Bag3) were investigated using immunofluorescence and immunoblotting assays. RESULTS: Cell viability assay and Western blot analysis showed that combined treatment with BJIGT and RZ suppressed LPS-induced cell death and expression of cell death-related proteins, including Bax, caspase 1, and DJ1 (P<0.05 or P<0.01). Immunofluorescence and immunoblotting assays showed that combined treatment with BJIGT and RZ reduced LPS-induced formation of TDP-43 aggregates and regulated autophagy-related protein levels, including p62, light chain 3b, Bag3, and ATG7, in TDP-43-expressing cells (P<0.05 or P<0.01). CONCLUSION: The combined treatment of BJIGT and RZ might reduce inflammation and regulate autophagy dysfunction in TDP-43-induced ALS.

Efficacy of Buzhong Yiqi decoction on benign prostatic hyperplasia and its possible mechanism.

OBJECTIVE: To explored the mechanism of Buzhong Yigi decoction ( BZYQD) in inhibiting prostatic cell proliferation effect. METHODS: The compounds of BZYQD consisted with eight herbs were searched in TCMSP databases and the putative targets of BZYQD were collected in Drugbank database. Then, "Benign prostatic hyperplasia" (BPH) was used to find the targets based on the GeneCards, Online Mendelian Inheritance in Man (OMIM) and Therapeutic Target Database (TTD) databases, and they were further used to collect further collect the intersection targets between BZYQD and BPH by counter-selection. Next, Herb-Compound-Target-Disease network was constructed by Cytoscape software and protein interaction network was built by Search tool for recurring instances of neighbouring genes (STRING) database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed by Database for Annotation, Visualization and Integrated Discovery (DAVID) database to predict the mechanism of the intersection targets. Mitogen activated protein kinase 8 (MAPK8), interleukin 6 (IL-6) and quercetin were chosen to perform molecular docking. Then 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was to detect the bility of BPH-1 (BPH epithelial cell line) by treated with quercetin at the concentrations of 15, 30, 60, 120 µM for 12, 24, 48, 72 h. The production of IL-6, tumor necrosis factor-α (TNF-α), IL-1ß and were mRNA expression detected by enzyme-linked immunosorbent assay kit and quantitative real-time polymerase chain reaction. Western blot was used to detect the expression of phospho-p38 mitogen-activated protein kinase (p-P38) and matrix metalloprotein-9 (MMP-9). RESULTS: A total 151 chemical ingredients of 8 herbs and 1756 targets in BZYQD, 105 common targets of BZYQD and BPH which mainly involving with MAPK8, IL-6, and so on. GO enrichment analysis got 352 GO entries (0.05) which included 208 entries of biological process, 64 entries of cell component and 80 entries of molecular function. KEGG pathway Enrichment analyses got 20 significant pathways which mainly involved with MAPK signaling way. MTT assay indicated quercetin inhibited the viability of BPH-1 cells by time-and dose-dependent manner. Quercetin decreased the IL-6, TNF-α and IL-1ß production and mRNA expression, and the expression of p-P38 and MMP-9 were also obviously reduced after treated with quercetin. CONCLUSIONS: BZYQD inhibited BPH through suppressing inflammatory response which might involving with regulating the MAPK signaling way.

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.

Deciphering the protective effect of Buzhong Yiqi Decoction on osteoporotic fracture through network pharmacology and experimental validation.

BACKGROUND: Osteoporotic fracture (OPF) is one of the most common skeletal diseases in an aging society. The Chinese medicine formula Buzhong Yiqi Decoction (BZYQD) is commonly used for treating OPF. However, the essential bioactive compounds and the underlying molecular mechanisms that promote fracture repair remain unclear. METHODS: We used network pharmacology and experimental animal validation to address this issue. First, 147 bioactive BZYQD compounds and 32 target genes for treating OPF were screened and assessed. A BZYQD-bioactive compound-target gene-disease network was constructed using the Cytoscape software. Functional enrichment showed that the candidate target genes were enriched in oxidative stress- and inflammation-related biological processes and multiple pathways, including nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD. RESULTS: The results revealed that BZYQD ameliorated OPF characteristics, including femoral microarchitecture, biomechanical properties, and histopathological changes, in a dose-dependent manner. Results of enzyme-linked immunosorbent assay showed that BZYQD reduced the serum's pro-inflammatory cytokines [Tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-1ß, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-κB in OPF rat femurs, suppressed NF-κB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways. CONCLUSIONS: Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-κB and activating Nrf2/MAPK signaling pathways.

Effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease. Methods:From April to June 2021, 60 specific pathogen-free Wistar rats were selected for this study. They were randomly divided into blank control, model, traditional Chinese medicine, and western medicine groups with 15 rats per group. Rat models of chronic obstructive pulmonary disease with lung and spleen deficiency were established in all groups except the blank control group. Rat models in the traditional Chinese medicine and western medicine groups were administered modified Buzhong Yiqi Decoction and synbiotics. Rat models in the model and blank control groups were identically administered 0.9% sodium chloride injection. After 7 days, the feces of rats in each group were collected for 16S rRNA sequencing of intestinal flora. Effective sequences were clustered to obtain operational taxonomic units for principal coordinate analysis, species composition analysis, and alpha diversity analysis. The effects of modified Buzhong Yiqi Decoction on the structure, diversity, and abundance changes of intestinal flora were analyzed. Results:The dominant bacteria in the traditional Chinese medicine and western medicine groups were Firmicutes, while the dominant bacteria in the blank control and model groups were Bacteroides. The dominant bacterial groups in each group were mainly Lactobacillus and Bacteroides. Alpha diversity analysis showed that the Shannon index in the community diversity indices of traditional Chinese medicine, western medicine, and blank control groups was (3.65 ± 0.35), (3.65 ± 0.36), and (3.59 ± 0.20), respectively, which were significantly higher than (3.37 ± 0.26) in the model group ( t = 2.49, 2.44, 2.60, all P < 0.05). There was no significant difference in the Shannon index among traditional Chinese medicine, western medicine, and blank control groups (all P > 0.05). The Sobs index of the traditional Chinese medicine, western medicine, and blank control group was (458.67 ± 73.11), (454.80 ± 95.13), and (525.93 ± 101.88), respectively, which were significantly higher than (337.40 ± 37.49) in the model group ( t = 5.72, 4.45, 6.73, all P < 0.05). The Sobs index in the blank control group was higher than that in the western medicine group. There was no significant difference in the Sobs index between blank control and traditional Chinese medicine groups and between western medicine and traditional Chinese medicine groups (both P > 0.05). Principal coordinate analysis revealed that compared with the blank control group, Actinomycetes decreased and Proteobacteria and Desulfurization bacteria increased at the phylum level in the model group, while compared with the blank control group, Bacteroides, Rombutzia,Trichospirillus, and Parabacteroides increased, and Prevotella, Clostridium, Brucella, and Ruminococcus decreased at the genus level. Compared with the western medicine group, Bacillus, Prevotella, Brucella, and Prevotellidae in the traditional Chinese medicine group increased, while Clostridium, Pectinobacter, Christensen, and Trichospirillus decreased in the traditional Chinese medicine group. There was a statistically significant difference in the composition of the bacterial population between groups (all P < 0.05). Conclusion:There is an imbalance in intestinal microecology in a rat model of chronic obstructive pulmonary disease. Modified Buzhong Yiqi Decoction can regulate the intestinal microecology environment, improve the structure of intestinal flora, and increase the diversity and abundance of intestinal flora.

Clinical Study on the Treatment of Female Stress Urinary Incontinence With Modified Buzhong Yiqi Decoction.

Purpose: To study the clinical application value of Modified Buzhong Yiqi Decoction in the treatment of female stress urinary incontinence (SUI). Methods: A total of 103 female patients with SUI were included in this study, 13 were lost to follow-up, and the final number of studies was 90. General information about the patients, including age, years of menopause, body mass index (BMI), reproductive history, chronic respiratory disease, hypertension, and diabetes, were recorded. All the patients were treated with Modified Buzhong Yiqi Decoction alone for 4 weeks. The Patient Global Impression of Improvement (PGI-I), the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICI-QSF) and 72-h voiding diary were used to evaluate the patients' subjective symptoms and urinary incontinence degree before treatment, 1 month after treatment and 1 year after treatment, the efficacy and efficacy-related factors of Modified Buzhong Yiqi Decoction in the treatment of female SUI were analyzed. Results: One month after Modified Buzhong Yiqi Decoction treatment, compared with before treatment, the PGI-I questionnaire was very much better (68.89%), much better (8.89%), a little better (12.33%), no change (8.89%), the ICI-QSF score decreased (P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); One year after treatment compared with before treatment, the PGI-I questionnaire was very much better (40.00%), much better (17.78%), a little better (12.22%), no change (30.00%), the ICI-QSF score decreased (P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); and 1 year after treatment compared with 1 month after treatment, the ratio of very much better at 1 year after treatment was significantly decreased (P < 0.05), the score of the ICI-QSF was significantly increased (P < 0.05), and 72-h urine leakage frequency was significantly increased (P < 0.05). The correlation analysis showed that the efficacy at 1 month after treatment was negatively correlated with the severity of SUI and chronic respiratory diseases, but was not significantly correlated with age, menopause status, BMI, number of pregnancies, and number of births. The efficacy at 1 year after treatment was negatively correlated with the severity of SUI, chronic respiratory disease, age, and number of births and was positively correlated with BMI, but not significantly correlated with menopause status and number of pregnancies. Conclusion: Modified Buzhong Yiqi Decoction can effectively treat SUI in women. The efficacy is related to the severity of SUI and chronic abdominal hypertension, but the long-term efficacy decreases.

Effectiveness of modified Buzhong Yiqi decoction in treating myasthenia gravis: study protocol for a series of N-of-1 trials.

BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease with high heterogeneity. The disease is chronic, relapsing repeatedly and progressive with acute exacerbation occasionally. Although the treatment of MG has developed, it is still unsatisfactory and has some unexpected side effects. Traditional Chinese medicine (TCM) has shown great potential in MG treatment, including relief of muscle weakness syndrome, improvement of patient's quality of life, and reduction of side effects of western medicine. The purpose of this study is to evaluate the effectiveness of modified Buzhong Yiqi decoction (MBYD) as an add-on therapy for MG through a small series of N-of-1 trials. METHODS: Single-centre, randomized, double-blind, 3 crossover N-of-1 trials will be conducted to enroll patients with MG diagnosed as spleen-stomach deficiency syndrome or spleen-kidney deficiency syndrome in TCM. Each N-of-1 trial has 3 cycles of two 4-week periods containing the MBYD period and placebo period. The wash-out interval of 1 week is prior to switching each period. PRIMARY OUTCOME: quantitative myasthenia gravis (QMG). SECONDARY OUTCOMES: the following scales: myasthenia gravis composite (MGC), myasthenia gravis activities of daily living profile (MG-ADL), myasthenia gravis quality of life (MG-QOL); the level of CD4+FoxP3+Treg cells and cytokines (IL-4, IL-17A, INF-γ, TGF-ß) in the peripheral blood; the alterations of the composition of gut microbiota; reduction of the side effects of western medicine. DISCUSSION: Used by WinBUGS software, we will conduct a hierarchical Bayesian statistical method to analyze the efficacy of MBYD in treating MG in individuals and populations. Some confounding variables such as TCM syndrome type and potential carryover effect of TCM will be introduced into the hierarchical Bayesian statistical method to improve the sensitivity and applicability of the trials, and the use of prior available information within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. We assumed that this study would reveal that MBYD is effective for MG and provide robust evidence of the efficacy of TCM to treat MG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ID: ChiCTR2000040477 , registration on 29 November 2020.

The protective effect of Buzhong Yiqi decoction on ischemic stroke mice and the mechanism of gut microbiota.

Buzhong Yiqi decoction (BZYQD) has been developed for preventing or reducing the recurrence of ischemic stroke for a long time in China. However, the mechanism of action of the BZYQD is not completely understood. Our research aims to determine whether the mechanism of action of BZYQD is by regulating gut microbiota using 16SR RNA and fecal microbiota transplantation. In a cerebral ischemia mouse model, the results showed that prophylactic administration of BZYQD could reduce brain infarct volume and improve neurological function and behavior. The prophylactic administration of BZYQD could regulate intestinal microbiota and increase the abundance of butyrate-producing Prevotellaceae_NK3B31_group and probiotic Akkermansia in mice 72 h after surgery. Transplanting BZYQD-administered bacterial flora into antibiotic-depleted mice could reproduce the therapeutic effects of BZYQD. Overall, our study provided molecular insights into the mechanism and impact of BZYQD in the prevention of cerebral ischemic damage and highlighted the potential of regulation of intestinal microbiota as a therapeutic approach for ischemic stroke.

The effects of modified Buzhong Yiqi decoction combined with Gangtai ointment on the wound healing and anal function in circumferential mixed hemorrhoid patients.

OBJECTIVE: To investigate the effects of modified Buzhong Yiqi decoction combined with Gangtai ointment on the wound healing and anal function of circumferential mixed hemorrhoid patients. METHODS: Patients (n=120) with circumferential mixed hemorrhoids were recruited as the research cohort. All the patients underwent surgical treatment and were randomly divided into a control group and a research group. The control group was administered chitosan hydrogels for wound healing, once a day. The research group was administered modified Buzhong Yiqi decoction (1 dose a day, orally) combined with Kangtai ointment for external application (twice a day, for two consecutive weeks). We compared the two groups' effective rates, their pain indexes, their perianal edema scores, their quality of life scores, their wound healing times, their pain resolution times, their anal functions, their wound exudate scores, and their adverse reactions. RESULTS: Compared with the control group, the research group had a higher effective rate (P<0.01), a lower pain index, and a lower perianal edema score (both P<0.001), a higher quality of life score (P<0.001), a shorter wound healing time, a shorter pain resolution time, and fewer adverse reactions than the control group (both P<0.001). The lengths of the anal canals in the research group were shorter than they were in the control group (P<0.01), and the resting pressure, maximum diastolic blood pressure, and maximum systolic blood pressure were higher than they were in the control group (all P<0.001). The wound exudate scores at 7 and 14 days after the treatment in the research group were lower than they were in the control group (all P<0.001). There were fewer adverse reactions in the research group than there were in the control group (P<0.05). CONCLUSION: Modified Buzhong Yiqi decoction combined with Gangtai ointment for patients with circumferential mixed hemorrhoids has good short-term efficacy. It helps to promote wound healing, improves anal function, and does not increase the incidence of adverse reactions. It is worthy of promotion and application.

[Systematic review and Meta-analysis on efficacy and safety of Buzhong Yiqi Decoction for stable chronic obstructive pulmonary disease].

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

Systematic review and Meta-analysis on efficacy and safety of Buzhong Yiqi Decoction for stable chronic obstructive pulmonary disease / 中国中药杂志

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

Treatment of hospital-acquired pneumonia with multi-drug resistant organism by Buzhong Yiqi decoction based on Fuzheng Quxie classical prescription: study protocol for a randomized controlled trial.

BACKGROUND: Drug resistance in China is becoming a more and more serious issue. Infection by drug-resistant bacteria has become a major disease that seriously threatens the health of Chinese people and affects national medical finance. Therefore, it is of great scientific and clinical significance to actively carry out research on the prevention and treatment of infections by multi-drug resistant organisms (MDRO). Previous studies by the authors suggested that patients with hospital-acquired pneumonia caused by MDRO mostly showed the pathological state of "insufficient healthy Qi and internal accumulation of pathogenic Qi" and "acute deficiency syndrome" mainly characterized by Qi deficiency. Buzhong Yiqi decoction is a famous classic prescription in traditional Chinese medicine (TCM) for treating internal damage fever. This study intends to provide an evidence-based rationale for Buzhong Yiqi decoction in treating MDRO hospital-acquired pneumonia by conducting a multi-center randomized controlled clinical study. METHODS/DESIGN: This study is designed to be a multi-center randomized controlled study in which patients are assigned randomly into control (standard therapy) and trial (standard therapy plus Buzhong Yiqi decoction) groups. The patients will be selected from the emergency department and the ICU inpatient department of five study sites and will all be diagnosed with MDRO hospital-acquired pneumonia and meet the inclusion criteria. Forty patients are to be enrolled in each study site, resulting in a total of 200 patients in the study. The treatment course is 28 days. DISCUSSION: In this study: (1) the theory of "acute Qi deficiency" in MDRO hospital-acquired pneumonia is put forward for the first time, and the basic theories of TCM are further improved; (2) a multi-center randomized controlled clinical study will be performed for the first time with Buzhong Yiqi decoction, the classic prescription for reinforcing healthy Qi and eliminating pathogenic Qi, providing a reliable evidence-based rationale for the treatment of MDRO pulmonary infection with TCM; (3) the clinical application and modern disease spectrum of Buzhong Yiqi decoction is expanded, and the scientific notion of "treating different diseases with the same method" is enriched further. TRIAL REGISTRATION: China Clinical Trial Registry, ChiCTR1900022429. Registered on April 11, 2019. http://www.chictr.org.cn/listbycreater.aspx.

[Effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrical stimulation on early stage postpartum pelvic floor dysfunction].

To investigate the curative effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrostimulation on early postpartum pelvic floor dysfunction disease (PFD) and its effect on the expression of transforming growth factor (TGF-ß1), matrix metalloprotein (MMP-2), and tissue inhibitor of metalloproteinase (TIMP-2). A total of 186 PFD patients admitted to our hospital from March 2014 to December 2016 were selected in the study and were randomly divided into test group (n=93) and control group (n=93). The control group received pelvic floor muscle exercises-biofeedback-electrostimulation, while the test group was additionally treated with modified Buzhong Yiqi decoction based on the treatment in control group. Then the clinical efficacy was compared between two groups. The results showed that vaginal contractile electromyography (EMG), duration of vaginal constriction, dynamic vaginal pressure and pelvic floor myoelectric activity in the test group at 1, 3 and 6 months after treatment were significantly higher than those before treatment and the control group (P<0.05). The effective rate for urinary incontinence was 97.14% in test group, significantly higher than 75.68% in the control group (P<0.05). The effective rate for improvement of sexual life quality was 96.43% in test group, significantly higher than 74.07% in control group (P<0.05). 1, 3 and 6 months after treatment, the uterine prolapse, posterior wall prolapse and anterior wall prolapse grade in test group was slightly lower than that in the control group, but the difference was not statistically significant. After treatment, the levels of TGF-ß1 and TIMP-2 in the test group were higher than those in the control group, while the levels of MMP-2 were lower than those in the control group (P<0.05). The results showed that modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrostimulation can effectively relieve the clinical symptoms, promote the body recovery and improve the quality of sexual life in PFD patients, with remarkable advantages, so it is worthy of popularizing.

One Case of Buzhong Yiqi Decoction Adding Gardeniae Fructus for Treatment of Acute Suppurative Otitis Media / 中国中医药信息杂志

The article mainly discussed the method and prescription of Buzhong Yiqi Decoction adding Gardeniae Fructus for the treatment of acute suppurative otitis media. The author summarized the pharmacological effects, clinical efficacy and application of Buzhong Yiqi Decoction by searching relevant literature,and proposed that weak spleen and stomach and imbalance of yin and yang are the pathogenesis in clinic,which can be treated with Buzhong Yi q i Decoction.