Bile acid metabolism in health and ageing-related diseases.

Bile acids (BAs) have surpassed their traditional roles as lipid solubilizers and regulators of BA homeostasis to emerge as important signalling molecules. Recent research has revealed a connection between microbial dysbiosis and metabolism disruption of BAs, which in turn impacts ageing-related diseases. The human BAs pool is primarily composed of primary BAs and their conjugates, with a smaller proportion consisting of secondary BAs. These different BAs exert complex effects on health and ageing-related diseases through several key nuclear receptors, such as farnesoid X receptor and Takeda G protein-coupled receptor 5. However, the underlying molecular mechanisms of these effects are still debated. Therefore, the modulation of signalling pathways by regulating synthesis and composition of BAs represents an interesting and novel direction for potential therapies of ageing-related diseases. This review provides an overview of synthesis and transportion of BAs in the healthy body, emphasizing its dependence on microbial community metabolic capacity. Additionally, the review also explores how ageing and ageing-related diseases affect metabolism and composition of BAs. Understanding BA metabolism network and the impact of their nuclear receptors, such as farnesoid X receptor and G protein-coupled receptor 5 agonists, paves the way for developing therapeutic agents for targeting BA metabolism in various ageing-related diseases, such as metabolic disorder, hepatic injury, cardiovascular disease, renal damage and neurodegenerative disease.

[Outcomes and measurements of randomized controlled trial for traditional Chinese medicine in treatment of endometriosis].

This study aims to analyze the outcomes and measurements of randomized controlled trial(RCT) for traditional Chinese medicine(TCM) treatment of endometriosis(EM) and provide a basis for the building of the core outcome set(COS) of EM. The RCT for TCM treatment of EM was retrieved from medical literature databases with the time interval from inception to February 3, 2022. The Cochrane risk of bias assessment tool was employed to evaluate the risk of bias of the included RCT, and descriptive analyses of the extracted information were carried out. A total of 519 RCTs were included, with the sample sizes ranging from 28-582 patients and 239 outcome indicators(8 outcome indicators per RCT on average). According to the functional properties, the reported outcome indicators were classified into 7 indicators: clinical efficacy assessment, indicators of clinical symptoms and signs, TCM symptom efficacy indicators, physical and chemical examinations, quality of life, long-term prognosis, and safety events. All the 519 RCTs had problems, such as the lack of differentiation between primary and secondary outcome indicators(1.73% RCTs reported such differen-tiation), poor quality, confused criteria for composite outcome indicators and arbitrary combination of indicators(45 criteria for the single outcome indicator of efficiency), and messy measurements(as many as 18 measurements for TCM symptom score). In addition, as a chronic disease, EM requires long-term management. The outcome indicators vary for the patients in different disease stages, such as EM pain, EM infertility, and post-operative EM, while the specific outcome indicator sets for different EM populations remain to be developed. In addition, the time point of measurement for EM long-term outcomes remains unclear, and the definition of TCM syndromes lacks standards. The RCT for TCM treatment had a variety of problems, such as the lack of differentiation of outcome indicators, confusion in criteria and measurements, lack of specific outcome indicator sets for different EM populations, and unclear time points for long-term outcomes. Therefore, the studies about COS need to be carried out urgently.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

Chinese Medicine in Management of Chronic Disease Endometriosis.

Endometriosis (EM), a refractory, highly recurrent and life-threatening chronic disease, requires long-term management and long-term drug treatment. Our previous studies showed that Chinese medicine (CM) can inhibit the postoperative recurrence of EM, improve quality of life, shorten the time to conception and increase pregnancy rates. CM produces few adverse reactions with high safety. These characteristics might be associated with the mechanism of CM's inhibition of recurrence. Therefore, we believe that CM may represent a good choice for long-term drug treatment and is worthy of clinical application.

Strategies for Activating Blood Circulation-Regulating Gan (Liver)-Tonifying Shen (Kidney) Sequential Therapy of Endometriosis-Associated Infertility.

Endometriosis (EM) is a major cause of infertility and has a complex pathogenesis, which brings severe challenges in both clinical treatment and scientific research. Current clinical research focuses on the difficult problem of improving the pregnancy rate of EM patients. Our studies found that Chinese medicine has significant advantages in terms of improving the pregnancy rate of EM patients.

LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.

BACKGROUND: This study aims to clarify the underlying mechanism for the tumor suppressive function of lnc TUSC7 in chemotherapy resistance of esophageal squamous cell carcinoma (ESCC). METHODS: TUSC7, miR-224 and DESC1 expressions in ESCC tissues and cells were detected by qRT-PCR. Protein level of DESC1, EGFR and p-AKT were observed by Western blot. Overall survival was calculated using the Kaplan-Meier method. Dual-luciferase reporter gene assay and RIP assay were used to comfirm TUSC7 binding to miR-224, and miR-224 binding to DESC1. Cell proliferation, apoptosis, and colony formation was detected by MTT, Flow Cytometry and Colony formation assays. RESULTS: TUSC7 was downregulated in ESCC tissues and cells, and low TUSC7 indicated worse overall survival. The analysis of bioinformatics softwares showed that TUSC7 specifically bound to miR-224, and we proved miR-224 was upregulated in ESCC and negatively correlated with TUSC7 expression. Overexpression of TUSC7/inhibition of miR-224 suppressed cell proliferation, colony formation and chemotherapy resistance of ESCC cells, and promoted cell apoptosis. In addition, we confirmed that miR-224 specifically bound to DESC1, and negatively correlated with DESC1. TUSC7 suppressed the proliferation and chemotherapy resistance of ESCC cells by increasing DESC1 expression via inhibiting miR-224. We also confirmed DESC1 inhibited chemotherapy resistance of ESCC cells via EGFR/AKT. Finally, in vivo experiments demonstrated that overexpression of TUSC7 decreased tumor growth and chemotherapy resistance. CONCLUSION: These findings suggested TUSC7 suppressed chemotherapy resistance of ESCC by downregulating miR-224 to modulate DESC1/EGFR/AKT pathway.

[Advantages and evidences research on Chinese medicine for treatment of pelvic inflammatory disease].

Pelvic inflammatory disease is an infectious disease. At present, Western medicine is mainly treated with antibiotics. However, the situation of antibiotics abuse is so grim that the potential risks such as the imbalance of bacteria, the resistance of bacteria, the production of super bacteria and the increase of adverse reactions are becoming more and more serious. Therefore, it is urgent to find a way to supplement or substitute antibiotics for the treatment of this disease. Traditional Chinese medicine treatment of the disease is effective and has its unique advantages. This paper mainly discusses the advantages and evidences of traditional Chinese medicine (TCM) treatment of pelvic inflammatory disease, to further prove the effectiveness and safety of TCM treatment and to provide medical evidence of reducing antibiotics use.

BC200 LncRNA a potential predictive marker of poor prognosis in esophageal squamous cell carcinoma patients.

OBJECTIVE: To explore the expression and prognosis significance of BC200 in esophageal squamous cell carcinoma (ESCC) patients who received radical resection. METHODS: We used quantitative real-time polymerase chain reaction to detect the expression level of BC200 in cancer tissue and paired adjacent normal tissue samples from 70 ESCC patients who received radical surgical resection and analyzed the correlation of the relative expression level of BC200 with clinical-pathological features and prognosis. RESULTS: We found that the relative expression of BC200 was significantly higher in ESCC tissues compared with adjacent normal tissue samples (P=0.023). But the expression of BC200 were not related to clinical-pathological features, such as age, TNM stages, and histological grade (P>0.05). Kaplan-Meier analysis showed that high expression levels of BC200 were correlated with poor prognosis in ESCC patients. Patients with a high level of BC200 had a shorter disease-free survival and overall survival than those with low BC200 expression (P=0.034 and P=0.031, respectively). On multivariate analysis, the hazard ratio (HR) of BC200 expression was 2.17 (95% confidence interval [CI]=1.12-4.19, P=0.022) for disease-free survival and 2.24 (95% CI=1.12-4.49, P=0.023) for overall survival. CONCLUSION: Our results indicate that high expression of BC200 reflects poor prognosis and could serve as a novel predictive marker for ESCC patients who received radical resection.

Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression.

AIM: Multi-drug resistance poses a critical bottleneck in chemotherapy. Given the up-regulation of mTOR pathway in many chemoresistant cancers, we examined whether sirolimus (rapamycin), a first generation mTOR inhibitor, might induce human osteosarcoma (OS) cell apoptosis and increase the sensitivity of OS cells to anticancer drugs in vitro. METHODS: Human OS cell line MG63/ADM was treated with sirolimus alone or in combination with doxorubicin (ADM), gemcitabine (GEM) or methotrexate (MTX). Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. MiRNAs in the cells were analyzed with miRNA microarray. The targets of miR-34b were determined based on TargetScan analysis and luciferase reporter assays. The expression of relevant mRNA and proteins was measured using qRT-PCR and Western blotting. MiR-34, PAK1 and ABCB1 levels in 40 tissue samples of OS patients were analyzed using qRT-PCR and in situ hybridization assays. RESULTS: Sirolimus (1-100 nmol/L) dose-dependently suppressed the cell proliferation (IC50=23.97 nmol/L) and induced apoptosis. Sirolimus (10 nmol/L) significantly sensitized the cells to anticancer drugs, leading to decreased IC50 values of ADM, GEM and MTX (from 25.48, 621.41 and 21.72 µmol/L to 4.93, 73.92 and 6.77 µmol/L, respectively). Treatment of with sirolimus increased miR-34b levels by a factor of 7.5 in the cells. Upregulation of miR-34b also induced apoptosis and increased the sensitivity of the cells to the anticancer drugs, whereas transfection with miR-34b-AMO, an inhibitor of miR-34b, reversed the anti-proliferation effect of sirolimus. Two key regulators of cell cycle, apoptosis and multiple drug resistance, PAK1 and ABCB1, were demonstrated to be the direct targets of miR-34b. In 40 tissue samples of OS patients, significantly higher miR-34 ISH score and lower PAK5 and ABCB1 scores were detected in the chemo-sensitive group. CONCLUSION: Sirolimus increases the sensitivity of human OS cells to anticancer drugs in vitro by up-regulating miR-34b interacting with PAK1 and ABCB1. A low miR-34 level is an indicator of poor prognosis in OS patients.

Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medicine.

OBJECTIVE: To compare the clinical effect of Chinese medicine (CM) and Western medicine (WM) for controlling the recurrence of pelvic endometriosis after a conservative operation. METHODS: The study was a multi-center, randomized, parallel controlled and prospective clinical trial. Patients were randomly divided into two groups: CM group (106 cases) and WM group (102 cases). Drugs were given to patients during 1-5 days of the first menstruation after a conservative operation in both groups. Patients with stages I and II (revised American Fertility Society) were treated for 3 months, while the patients with stages III and IV were treated for 6 months. The patients in the CM group were treated using three types of Chinese herbal medicine based on syndrome differentiation. Patients in the WM group were treated using gonadotropin releasing hormone agonist (GnRH-a) or gestrinone. Patients treated with GnRH-a received add-back therapy of Tibolone Tablets once a day after 4 months of treatment. Any cases of dysmenorrheal chronic pelvic pain, menstruation and any adverse reactions of patients were recorded once a month during the preoperative and postoperative periods and once every 3 months during the follow-up period. During the preoperative, postoperative and the follow-up periods, patients underwent type B ultrasonography of the pelvis and measurements of serum CA125 levels, gynecologic examination, routine evaluations of blood, urine, hepatic function (glutamate pyruvate transaminase), renal function (blood urea nitrogen) and electrocardiograms. During the follow-up period they underwent type B pelvic ultrasonography, measurement of serum CA125 levels and further gynecologic examinations. The two treatments were compared for clinical recurrence rates, pregnancy rates and the incidence of adverse reactions. RESULTS: The incidence and timing of recurrence of endometriosis were not significantly different between the two groups. The first pregnancy achieved by the patient in the CM group was significantly earlier than that in the WM group (P <0.05). Moreover, the incidence of adverse reactions in the WM group was significantly higher than in the CM group (P <0.01). CONCLUSIONS: Treatment with Chinese herbal medicines prevented the recurrence of endometriosis after a conservative operation, improved the conception rate and showed fewer and lighter adverse reactions than did treatment with WM therapy. Treatment with Chinese herbal medicine meets the need of patients wishing to have a child following endometriosis and is an appropriate form of clinical treatment.

Chinese medicine improves postoperative quality of life in endometriosis patients: a randomized controlled trial.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) and Western medicine (WM) on quality of life (QOL) after conservative surgery for endometriosis. METHODS: A total of 320 patients with endometriosis were randomized into two groups by using random block design, CM group (160 cases, activating blood circulation and removing blood stasis treatment based on syndrome differentiation) and WM group (160 cases, gonadotropin-releasing hormone agonist or gestrinone treatment) after conservative surgery. Treatment was given for 3-6 months (according to the revised American Fertility Society scoring system stage), and the World Health Organization QOL-BREF (WHOQOL-BREF) was applied to patients before and after treatment to assess QOL. RESULTS: There were 136 cases in the CM group and 141 cases in the WM group completing therapy. In the CM group, the use of the WHOQOL-BREF showed that the physical, psychological and environmental scores posttreatment were significantly higher than those at pre-treatment (P < 0.05), and for 12 items (pain and discomfort, energy and fatigue, sleep and rest, mobility, activities of daily living, work capacity, negative feelings, health and social care: accessibility and quality, participation in and opportunities for recreation/leisure activities, appetite, QOL score, overall health status and QOL), the difference in scores was significant (P < 0.05). In the WM group, 4 items (pain and discomfort, opportunities for acquiring new information and skills, QOL score, overall health status and QOL) had significantly different scores post-treatment compared with those at pre-treatment (P < 0.05). Before treatment, the QOL in the two groups of patients showed no significant difference (P > 0.05). After treatment, the scores for physical health in the CM group were significantly higher than those of the WM group (P < 0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) in the CM group were significantly higher than those in the WM group (P < 0.05). CONCLUSIONS: CM and WM treatment could improve the QOL of patients with endometriosis after conservative surgery. CM treatment is more effective than WM.

[Detection and quantification of BCR-ABL transcripts in patients with chronic myeloid leukemia by real-time quantitative reverse transcriptase polymerase chain reaction].

OBJECTIVE: To investigate the effect of real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) approach in chronic myeloid leukemia (CML) for detecting the minimal residual disease (MRD) or monitoring the treatment response and predicting the prognosis. METHODS: Fifty-six CML patients, 39 males and 17 females, aged 39 (16 approximately 66), with disease history and frozen RNA specimens were studied, 31 of which were in the incipient chronic phase, 7 in the accelerated phase, and 17 in the rapidly progressing phase. Three or more frozen RNA specimens collected before and after treatment were preserved in 11 of the patients. Breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) of the patients in different CML stages was analyzed by RT-PCR approach. RESULTS: The BCR-ABL transcript of those patients remaining in chronic period after treatment decreased to 1/3 that of the baseline level six months after the initiation of treatment and then remained at that level. The BCR-ABL transcript of those in which progressing change occurred increased when such change occurred. After allogeneic transplantation of peripheral blood stem cells the BCR-ABL level decreased significantly. The median DoseN in the 17 progressing patients was 10 492, significantly higher than those of the 31 patients in chronic phase (5920) and in the 7 patients in accelerated phase (4444, both P < 0.05). The minimal residual disease and the treatment response were closely associated with the level and its variation of BCR-ABL transcripts, the transcripts level in blastic crisis was significantly higher than that in chronic phase or accelerated phase. CONCLUSION: Real-time quantitative RT-PCR is reliable and can be used to detect the minimal residual disease, monitor the treatment outcome, and predicting blastic crisis.

[Impact of non-target gene mutations and reduced permeability of outer membrane on quinolone resistance and multiple antibiotic resistance in Escherichia coli].

OBJECTIVE: To investigate the impact of non-target gene mutations and reduced permeability of the outer membrane on quinolone resistance and multiple antibiotic resistance (mar) in Escherichia coli. METHODS: Several high-level quinolone resistant isolates whose strains were accompanied by concurrent resistant to several antibiotics were selected. The PCR products of marOR region were sequenced to detect the possible gene changes and then the strains' outer membrane proteins (Omps) were extracted to analyze on the constitutive profiles. RESULTS: We found two site mutations in R410 isolate: 1,870(T-->C, Val-->Ala) and 1,879(A-->C, terminator-->Ser). The OmpF deficiency was found in all 3 resistant strains. CONCLUSION: The increased expression of MarA induced by gene mutations in marOR and the constitutive profile changes of the Omps (OmpF deficient strains) may play some role in the quinolone resistance and multiple antibiotic resistance of Escherichia coli.