Urogenital tract and rectal microbiota composition and its influence on reproductive outcomes in infertile patients.

Introduction: Microbiota in the human body are closely related to human diseases. Female urogenital tract and rectal microbes have been considered as important factors affecting female pregnancy, but the mechanism is unknown. Methods: Cervical, vaginal, urethral, and rectal swabs were collected from 22 infertile patients and 10 controls, and follicular fluid was extracted from 22 infertile patients. The microbial composition of different sampling sites of infertile patients was examined. By comparing the microbial composition difference between infertile patients and controls and combining bioinformatics methods to analyze the potential impact of the female urogenital tract (cervical, vaginal and urethral) and rectal microbial diversity on female infertility and pregnancy outcomes. Results: Lactobacillus predominated in the female urogenital tract, but its abundance decreased in infertile patients, whereas the abundance of Gardnerella and Atopobium increased. The microbial changes in the urethra had the same trend as that in the vagina. Compared with healthy controls, the cervical and rectal microbial diversity of infertile patients were significantly increased and decreased, respectively. There might be interactions between microbes in different parts of female. Geobacillus thermogeniticans was enriched in the urogenital tract and rectum of infertile patients, and has a good predictive effect on infertility. Compared with infertile patients, L. johnsonii was enriched in the vagina, urethra, and intestine of the control group. L. acidophilus in follicular fluid might be associated with Non-pregnancy. Conclusion: This study found that the microbial composition of infertile patients was changed compared with that of healthy people. The translocation of Lactobacillus between the rectum and urogenital tract might play a protective barrier role. The changes of Lactobacillus and Geobacillus might be related to female infertility or pregnancy outcome. The study provided a theoretical basis for the future treatment of female infertility from the perspective of microorganisms by detecting the microbial changes associated with female infertility.

Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing.

Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

Efficacy and Safety of Pentoxifylline for Venous Leg Ulcers: An Updated Meta-Analysis.

The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy-pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers. We systematically searched multiple electronic databases PubMed, Web of Science, Embase, the Cochrane Library, the Cochrane Central Register of Controlled Trials, China Science and Technology Journal Database, WanFang Data, China National Knowledge Infrastructure, and the Chinese Biomedical Literature Database to identify eligible studies. Randomized clinical trials of pentoxifylline versus placebo treatment in patients with venous leg ulcers were considered for inclusion. The primary outcomes included ulcer healing rate and the incidence of adverse events after treatment. The secondary outcomes were the ulcer significant improvement (the ulcer size shrank by more than 60% after treatment) rate, mean duration of complete wound healing and changes in mean ulcer size. A meta-analysis and qualitative analysis were conducted to estimate endpoints. A total of 13 randomized clinical trials, including 921 individuals, were finally included. Compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, P < .001) and significant improvement rate (RR = 2.36, 95%CI 1.31 to 4.24, P = .004) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, P = .04) at the same time. Moreover, pentoxifylline also shortened mean duration of complete wound healing (P = .007) and shrank ulcer size (P = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively. However, the evidence is insufficient to prove the results due to moderate-certainty evidence. Large-scale, well-designed randomized clinical trials are warranted.

[A Case of Pseudohypoaldosteronism Type â ¡ (PHA2) Caused by a Novel Mutation of KLHL3].

The patient, a 41-year-old woman, was admitted because "it was found out she had elevated serum potassium levels for 18 days". Eighteen days prior to admission at our hospital, the patient was found to have elevated serum potassium during hospitalization at another hospital, where the patient received symptomatic treatment and was discharged after her serum potassium returned to a normal level. However, the patient still had elevated serum potassium repeatedly and was referred to our hospital for further examination. The patient had a history of acute nephritis and gestational hypertension. Six months prior to admission at our hospital, it was found out that the patient had slightly elevated blood pressure, but no intervention was done. The patient's father has a history of hypertension and diabetes. After admission, laboratory results showed that the patient had hyperkalemia, hyperchloremia and metabolic acidosis. The level of plasma renin was obviously below the normal range, but the concentration of plasma aldosterone was within the normal range. A new mutation locus (c.1115delG) in KLHL3 (Kelch like family member 3) gene was revealed by genetic testing, leading to the diagnosis of pseudoaldosteronism type Ⅱ (PHA2). The patient was given regular treatment of oral hydrochlorothiazide hydrochloride at set intervals. Subsequently, her blood electrolyte level, blood pH, BE and BEB have returned to normal levels. The patient was followed up for 12 months and did not feel unwell during the follow-up period.

Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury.

Huaganjian decoction (HGJD) was first recorded in the classic "Jing Yue Quan Shu" during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.

Efficacy and Safety of Stem Cell Therapy for T1DM: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM. METHODS: We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), ß cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0. RESULTS: Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD = -1.20, 95% CI -1.91 to -0.49, P = 0.0009) and increase fasting C-peptide levels (MD = 0.25, 95% CI 0.04 to 0.45, P = 0.02) and AUCC (SMD = 0.66, 95% CI 0.13 to 1.18, P = 0.01). Stem cell therapy could also reduce insulin dosages (SMD = -2.65, 95% CI -4.86 to -0.45, P = 0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, P = 0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, P = 0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, P < 0.00001). CONCLUSION: Stem cell therapy for T1DM may improve glycemic control and ß cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.

Is the delivery mode a critical factor for the microbial communities in the meconium?

BACKGROUND: Mothers are the primary source of bacteria for newborns, but it is unclear whether mother-to-newborn transmission occurs prior to, during or after birth. Similarly, the effect of the delivery mode on neonatal microorganisms has been the focus of controversy. METHODS: Healthy maternal and neonatal pairs that underwent vaginal birth and caesarean section were enrolled in this study. Meconium, placenta, membrane and amniotic fluid samples for newborns and vaginal, rectal and oral samples for mothers were collected. All samples were amplified and sequenced by a 16S rRNA gene primer set targeting bacteria and archaea. FINDINGS: A total of 550 samples from 36 mother-neonate pairs with vaginal births and 42 mother-neonate pairs with caesarean sections were included in this study. The negative controls showed that the data analysis in this study was not affected by contamination. There was a high diversity of microbial communities in the pregnancy environment of the foetus. Meconium samples could be divided into three distinct types that were not influenced by the delivery method. INTERPRETATION: The distribution patterns of bacterial communities in the meconium, placenta, and foetal membranes were highly similar and had nothing to do with the mode of delivery. For approximately half of the placental microorganisms, the same sequence could be found in the vaginal, rectal, and oral samples of the mother.

Estimation of a safe level for occupational exposure to vinyl chloride using a benchmark dose method in central China.

OBJECTIVES: The aim of this study was to estimate a benchmark dose (BMD) for chromosome damage induced by vinyl chloride monomer (VCM) in VCM-exposed workers in central China and validate the published results in Shanghai. METHODS: VCM-exposed workers who had been exposed to VCM for at least one year (n=463) and matched subjects not exposed to VCM or other toxins (n=273) were asked to participate in this study. Micronucleus (MN) frequency based on the cytokinesis-block micronucleus assay (CBMN) was used as a biomarker for chromosome damage induced by VCM exposure. RESULTS: The MN frequency in the VCM-exposed workers was significantly higher than that in the control group, and multivariate Poisson regression suggested that gender, smoking status and VCM exposure were the significant factors influencing the risk of increased MN frequency. When subjects were further stratified according to gender and smoking status, the results showed that female VCM-exposed workers were more susceptible than the males to the risk of increased MN frequency. The MN frequency of smokers was significantly higher than that of nonsmokers in the control group. Our study also suggested that there was a strong dose-response relationship between VCM CED and the increased risk of MN frequency in the total group, males and females. The BMDL(10) was found to be 630.6, 670.2 and 273.7 mg-year for all VCM-exposed workers, males and females, respectively. CONCLUSIONS: These results invite further scrutiny of the current VCM occupational exposure limits and warrant further study of the risk of VCM genotoxicity and carcinogenicity.

[Analysis of musculoskeletal disorders, work load and working postures among manufacturing workers].

OBJECTIVE: To analyze the distribution of the musculoskeletal disorders, work load and working postures in different factories, gender, education levels, age and working years among manufacturing workers. METHODS: In a cross-sectional study of 5134 manufacturing workers in 12 factories, the morbidities for musculoskeletal disorders in one year period were measured with questionnaires. RESULTS: The morbidities for musculoskeletal disorders in body sites: waist, neck, shoulder, wrist, ankle/feet, knee, hip/buttocks and elbows were 59.7%, 47.9%, 38.1%, 33.7%, 26.9%, 25.4%, 15.2%, and 14.9%, respectively in one year period. There were significant differences of morbidities for musculoskeletal symptoms in body sites of workers among different factories (P < 0.05 or P < 0.01). The morbidities of musculoskeletal symptoms in elbows, waist, wrists and ankle/feet of the workers in refractory material and chemical fiber factories were higher than those in other factories, the morbidities for musculoskeletal symptoms of workers in garments and diamond factories were lower than those in other factories. The morbidities for musculoskeletal symptoms in neck, shoulders and wrists of female workers were significantly higher than those of male workers (P < 0.01). There were significant differences of the morbidities for musculoskeletal symptoms in body sites among workers with different educational levels (P < 0.05 or P < 0.01). There were significant differences of the morbidities for musculoskeletal symptoms in neck, shoulders, wrists, hip/buttocks and knee among groups with different age or different working years (P < 0.01), and the morbidities for musculoskeletal symptoms increased with age and working years. The proportions of unhealthy working postures and high working load among workers in refractory material and chemical fiber factories were higher; but those in garments and diamond factories were lower. CONCLUSION: The morbidities for musculoskeletal symptoms in waist, neck, shoulder and wrists of workers in manufacturing workers were higher; the gender, education level, age and working years could influenced the morbidities for musculoskeletal disorders.

[Association between occupational stress and musculoskeletal disorders in lower extremity].

OBJECTIVE: To explore the relationship between occupational stress and musculoskeletal disorders in lower extremity. METHODS: The cross-sectional study was used to investigate 5338 workers in 13 factories and companies for prevalence of musculoskeletal disorders in lower extremity, working postures and occupational stress were investigated with questionnaires for past year. Perceived occupational stress was evaluated by the Chinese version of the Job Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) Model Questionnaire. Logistic regression analyses were conducted to estimate the associations between occupational stress and prevalence of musculoskeletal disorders in lower extremity. RESULTS: In the main dimensions of job strain and ERI model, physical demands and effort were risk factors of hip disorders, but job control was a protective factor of hip disorders. When job strain and ERI model scales were analyzed simultaneously, only physical demands were risk factor of hip disorders. When job strain and the effort-reward imbalance were computed by creating four independent categories, job strain was a risk factor of hip disorders, ERI was a risk factor of hip and knee disorders. The risk of imbalance between job strain and effort-reward the protective effect of job control increased with the disorder regions. According to continuous variable analysis, job strain by calculated with physical demands was risk factor of hip disorders, continuous ERI variable was risk factor of hip and knee disorders. CONCLUSION: Occupational stress is associated significantly with musculoskeletal disorders in lower extremity. The control of occupational stress and increase of job control should be considered for preventing the musculoskeletal disorders in lower extremity.

[Gender difference of relationship between occupational stress and depressive symptoms].

OBJECTIVE: To explore gender difference of relationship between occupational stress and depressive symptoms. METHODS: The cross-sectional study was used to investigate 5338 workers in 13 factories and companies, the depressive symptoms were assessed with Epidemiologic Studies Depression Scale (CES-D) and the perceived occupational stress was evaluated by the Chinese version of the Job Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) Model Questionnaire. Logistic regression analyses were conducted to estimate the associations between occupational stress and prevalence of depressive symptoms. RESULTS: Prevalence of depressive symptoms was 31.8% for all subjects, 33.8% for males and 27.7% for females, gender difference of prevalence was significant (P < 0.01). Psychological demands, physical demands, job control, effort, overcommitment and negative affectivity scores for males were significantly higher than those for females(P < 0.01 or 0.05), social support, reward and job satisfaction scores for males were significantly lower than those for females (P < 0.01). Psychological demands, physical demands, job control, effort, overcommitment and negative affectivity scores for workers with depressive symptoms were significantly higher than those for workers without depressive symptoms (P < 0.01) but job control, social support, reward, job satisfaction and positive affectivity scores for workers with depressive symptoms were significantly lower than those for without depressive symptoms (P < 0.01). Psychological demands, physical demands, job control, effort, overcommitment and negative affectivity scores for male workers with depressive symptoms were significantly higher than those for female counterparts (P < 0.01), but social support, reward, job satisfaction scores for male workers with depressive symptoms were significantly lower than hose for female workers with depressive symptoms (P < 0.01). Ratio of male workers and male workers with depressive symptoms with job strain and ERI > 1, high demands and low control, and high effort and low reward were higher than female counterparts (P < 0.01). The risk of depressive symptoms for female with high demands and low control was about two times as high as that for female workers with low demands and high control for psychological demands and physical demands (OR = 2.0), risk for females was slightly higher than that for males (OR = 2.04 and 2.17, respectively). The risk of depressive symptoms for workers with high efforts and low rewards was about two times as high as that for workers with low efforts and high rewards (OR = 1.70). No interactive effect between gender and job strain and ERI on depressive symptoms were found. CONCLUSION: The gender difference of relationship between depressive symptom prevalence and job strain may due to the difference of psychosocial factors between females and males. There may be no interactive effect between psychosocial factors and gender on depressive symptoms.