Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis.

BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

ChemFLuo: a web-server for structure analysis and identification of fluorescent compounds.

BACKGROUND: Fluorescent detection methods are indispensable tools for chemical biology. However, the frequent appearance of potential fluorescent compound has greatly interfered with the recognition of compounds with genuine activity. Such fluorescence interference is especially difficult to identify as it is reproducible and possesses concentration-dependent characteristic. Therefore, the development of a credible screening tool to detect fluorescent compounds from chemical libraries is urgently needed in early stages of drug discovery. RESULTS: In this study, we developed a webserver ChemFLuo for fluorescent compound detection, based on two large and high-quality training datasets containing 4906 blue and 8632 green fluorescent compounds. These molecules were used to construct a group of prediction models based on the combination of three machine learning algorithms and seven types of molecular representations. The best blue fluorescence prediction model achieved with balanced accuracy (BA) = 0.858 and area under the receiver operating characteristic curve (AUC) = 0.931 for the validation set, and BA = 0.823 and AUC = 0.903 for the test set. The best green fluorescence prediction model achieved the prediction accuracy with BA = 0.810 and AUC = 0.887 for the validation set, and BA = 0.771 and AUC = 0.852 for the test set. Besides prediction model, 22 blue and 16 green representative fluorescent substructures were summarized for the screening of potential fluorescent compounds. The comparison with other fluorescence detection tools and theapplication to external validation sets and large molecule libraries have demonstrated the reliability of prediction model for fluorescent compound detection. CONCLUSION: ChemFLuo is a public webserver to filter out compounds with undesirable fluorescent properties, which will benefit the design of high-quality chemical libraries for drug discovery. It is freely available at http://admet.scbdd.com/chemfluo/index/.

Fat distribution measurements by chemical shift-encoded transition region extraction predict the risk of hyperglycaemia, dyslipidaemia and metabolic syndrome in mice.

Metabolically healthy or unhealthy obesity is closely related to metabolic syndrome (MetS). To validate a more accurate diagnostic method for obesity that reflects the risk of metabolic disorders in a pre-clinical mouse model, C57BL/6J mice were fed high-sucrose-high-fat and chow diets for 12 weeks to induce obesity. MRI was performed and analysed by chemical shift-encoded fat-water separation based on the transition region extraction method. Abdominal fat was divided into upper and lower abdominal regions at the horizontal lower border of the liver. Blood samples were collected, and the glucose level, lipid profile, liver function, HbA1c and insulin were tested. k-means clustering and stepwise logistic regression were applied to validate the diagnosis of hyperglycaemia, dyslipidaemia and MetS, and to ascertain the predictive effect of MRI-derived parameters to the metabolic disorders. Pearson or Spearman correlation was used to assess the relationship between MRI-derived parameters and metabolic traits. The receiver-operating characteristic curve was used to evaluate the diagnostic effect of each logistic regression model. A two-sided p value less than 0.05 was considered to indicate statistical significance for all tests. We made the precise diagnosis of obesity, dyslipidaemia, hyperglycaemia and MetS in mice. In all, 14 mice could be diagnosed as having MetS, and the levels of body weight, HbA1c, triglyceride, total cholesterol and low-density lipoprotein cholesterol were significantly higher than in the normal group. Upper abdominal fat better predicted dyslipidaemia (odds ratio, OR = 2.673; area under the receiver-operating characteristic curve, AUCROC = 0.9153) and hyperglycaemia (OR = 2.456; AUCROC = 0.9454), and the abdominal visceral adipose tissue (VAT) was better for predicting MetS risk (OR = 1.187; AUCROC = 0.9619). We identified the predictive effect of fat volume and distribution in dyslipidaemia, hyperglycaemia and MetS. The upper abdominal fat played a better predictive role for the risk of dyslipidaemia and hyperglycaemia, and the abdominal VAT played a better predictive role for the risk of MetS.

Pneumonia Is Associated with Increased Mortality in Hospitalized COPD Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at a heightened risk of pneumonia. Whether coexisting community-acquired pneumonia (CAP) can predict increased mortality in hospitalized COPD patients is still controversial. OBJECTIVE: This systematic review and meta-analysis aims to assess the association between CAP and mortality and morbidity in COPD patients hospitalized for acute worsening of respiratory symptoms. METHODS: In this review, cohort studies and case-control studies investigating the impact of CAP in hospitalized COPD patients were retrieved from 4 electronic databases from inception until December 2019. Methodological quality of included studies was assessed using Newcastle-Ottawa Quality Assessment Scale. The primary outcome was mortality. The secondary outcomes included length of hospital stay, need for mechanical ventilation, intensive care unit (ICU) admission, length of ICU stay, and readmission rate. The Mantel-Haenszel method and inverse variance method were used to calculate pooled relative risk (RR) and mean difference (MD), respectively. RESULTS: A total of 18 studies were included. The presence of CAP was associated with higher mortality (RR = 1.85; 95% CI: 1.50-2.30; p < 0.00001), longer length of hospital stay (MD = 1.89; 95% CI: 1.19-2.59; p < 0.00001), more need for mechanical ventilation (RR = 1.48; 95% CI: 1.32-1.67; p < 0.00001), and more ICU admissions (RR = 1.58; 95% CI: 1.24-2.03; p = 0.0002) in hospitalized COPD patients. CAP was not associated with longer ICU stay (MD = 5.2; 95% CI: -2.35 to 12.74; p = 0.18) or higher readmission rate (RR = 1.02; 95% CI: 0.96-1.09; p = 0.47). CONCLUSION: Coexisting CAP may be associated with increased mortality and morbidity in hospitalized COPD patients, so radiological confirmation of CAP should be required and more attention should be paid to these patients.

Prevalence and risk factors of nocturnal enuresis among children ages 5-12 years in Xi'an, China: a cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) has a negative impact on children's health and imposes a long-term burden on families. With economic development and cultural improvements, parents and medical professionals pay more attention to NE. The aim of this study was to investigate the prevalence and risk factors of NE among children ages 5-12 years in Xi'an, China. METHODS: A stratified cluster sampling method was used to conduct a cross-sectional study of NE in 10 kindergartens and 20 primary schools in Xi'an. We used univariate analysis to compare the prevalences of characteristics such as gender, duration of disposable diaper (DD) use, toilet training onset time, daily living habits, academic performance, and family history of NE. Logistic regression analysis was used to calculate odds ratio and to determine risk factors of NE. RESULTS: The study included 6568 children ages 5-12 years, of which 262 (3.99%) had NE. The prevalence rates of NE decreased with age, with the highest prevalence at age 5 (9.09% for boys; 6.03% for girls). However, the prevalence increased with duration of DD use. Children experienced more NE if they never accepted toilet training (7.83%) or if they drank sugary beverages during the day (5.36%). Sleep disorders, sweets intake, drinking low amounts of plain water during the day, and family history of NE, were statistically associated with NE. CONCLUSION: NE was closely associated with a family history of NE, being male, long-term use of DD, delayed toilet training, drinking sugary beverages and/or consuming little plain water, and sleep disorders. A supportive parental attitude towards NE and timely medical treatment can improve the quality of life of enuretic children.

In vivo and in vitro performance of a China-made hemodialysis machine: a multi-center prospective controlled study.

OBJECTIVE: To evaluate the in vivo and in vitro performance of a China-made dialysis machine (SWS-4000). METHODS: This was a multi-center prospective controlled study consisting of both long-term in vitro evaluations and cross-over in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V values, URR values, and dialysis-related adverse reactions in patients on maintenance hemodialysis, as well as the ultrafiltration rate, the concentration of electrolytes in the proportioned dialysate, the rate of heparin injection, the flow rate of the blood pump, and the rate of malfunction. RESULTS: The Kt/V and URR values at the 1st and 4th weeks of dialysis as well as the incidence of adverse effects did not differ between the two groups in cross-over in vivo tests (P > 0.05). There were no significant differences between the two groups in the error values of the ultrafiltration rate, the rate of heparin injection or the concentrations of electrolytes in the proportioned dialysate at different time points under different parameter settings. At weeks 2 and 24, with the flow rate of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis machine was significantly higher than that of the Fresenius 4008 dialysis machine (P < 0.05), but there was no significant difference at other time points or under other settings (P > 0.05). The malfunction rate was higher in the SWS-4000 group than in the Fresenius 4008 group (P < 0.05). CONCLUSIONS: The in vivo performance of the SWS-4000 dialysis machine is roughly comparable to that of the Fresenius 4008 dialysis machine; however, the malfunction rate of the former is higher than that of the latter in in vitro tests. The stability and long-term accuracy of the SWS-4000 dialysis machine remain to be improved.

Is COPD associated with increased mortality and morbidity in hospitalized pneumonia? A systematic review and meta-analysis.

This review aimed to investigate whether chronic obstructive pulmonary disease (COPD) is associated with increased mortality and morbidity in patients hospitalized with community-acquired pneumonia (CAP). EMBASE, PubMed and Web of Science were searched for cohort studies and case-control studies investigating the impact of COPD on CAP. The primary outcome was all-cause mortality, and secondary outcomes included length of hospital stay, intensive care unit (ICU) admission and need for mechanical ventilation. Methodological quality was assessed using the Newcastle-Ottawa Scale. The Mantel-Haenszel method and inverse variance method were used to calculate pooled relative risks (RRs) and mean differences (MD), respectively. Eleven studies (nine cohort studies and two case-control studies), involving 257 958 patients, were included. The overall methodological quality was high. COPD was not associated with increased mortality in hospitalized CAP patients (RR, 1.20; 95% confidence interval (CI): 0.92-1.56; P = 0.19; I(2) = 55%) in cohort studies, and was associated with reduced mortality in case-control studies (RR, 0.82; 95% CI: 0.74-0.90; P < 0.0001; I(2) = 80%). COPD was not associated with longer hospital stay (MD, 0.11; 95% CI: -0.42 to 0.64; P = 0.68; I(2) = 21%), more frequent ICU admission (RR, 0.97; 95% CI: 0.70-1.35; P = 0.87; I(2) = 65%), and more need for mechanical ventilation (RR 0.91, 95% CI: 0.71-1.16; P = 0.44; I(2) = 4%).The current available evidence indicates that COPD may not be associated with increased mortality and morbidity in patients hospitalized with CAP. This conclusion should be re-evaluated by prospective population-based cohort studies.

[Effects of "reinforcing Qi and activating blood" on stable chronic obstructive pulmonary disease (Qi deficiency and blood stasis syndrome].

OBJECTIVE: To study the clinical effects of "Reinforcing Qi and Activating Blood" in the treatment of stable chronic obstructive pulmonary disease (Qi Deficiency and Blood Stasis Syndrome). METHODS: This study recruit 50 outpatients with stabe chronic obstructive pulmonary disease (Qi Deficiency and Blood Stasis Syndrome), who were randomly divided into 2 groups, control group and treatment of "Reinforcing Qi and Activating Blood" group. The patients in control group were given conventional treatment, while the patients in treatment group not only received conventional treatment but also the treatment of Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets for 3 months. The duration of follow up was 12 months, and chinese medicine (CM) symptoms, cellular immunity indexes and haemodynamics indexes were assessed every 3 months. RESULTS: The total effective rate in treatment group at 3 months treatment and 3 months follow-up were higher than that in control group (P < 0.05). The CM symptoms in treatment group were improved significantly (P < 0.05). In treatment group, the level of CD4 and the ratio of CD4/CD8 after therapy were higher than those before (P < 0.05), and the level of CD8 was lower than that before (P < 0.05). The level of NO was no significant difference (P > 0.05), while the level of endothelin (ET) was significantly different (P < 0.05). The frequency of suffering from cold, the admission due to acute exacerbation and hospital stay in treatment group were all lower than those in control group (P < 0.05). CONCLUSION: The "Reinforcing Qi and Activating Blood" therapy can improve the symptoms and clinical curative effect of TCM in the treatment of stable COPD (Qi Deficiency and Blood Stasis Syndrome), with the improvement of their cellular immunological function and vasomotor function.

Risk of incident chronic kidney disease in metabolically healthy obesity and metabolically unhealthy normal weight: A systematic review and meta-analysis.

Studies have reported inconsistent results about the risk of incident chronic kidney disease (CKD) in people with metabolically healthy obesity (MHO). We designed this systematic review and meta-analysis to evaluate the risk of developing CKD in people with MHO and metabolically unhealthy normal weight (MUNW). We used a predefined search strategy to retrieve eligible studies from multiple databases up to June 20, 2022. Random-effects model meta-analyses were implied to estimate the overall hazard ratio (HR) of incident CKD in obesity phenotypes. Eight prospective cohort studies, including approximately 5 million participants with a median follow-up ranging between 3 and 14 years, were included in this meta-analysis. Compared to the metabolically healthy normal weight (MHNW), the mean differences in cardiometabolic and renal risk factors in MHO, MUNW, and metabolically unhealthy obesity (MUO) were evaluated with overall HR of 1.42, 1.49, and 1.84, respectively. Compared to MHNW, the mean estimated glomerular filtration rate (eGFR) and high-density lipoprotein (HDL) were significantly lower, and low-density lipoprotein (LDL), blood pressure, blood glucose, and triglycerides were higher in MHO and MUNW. In conclusion, MHO and MUNW are not benign conditions and pose a higher risk for incident CKD. Obesity, whether in the presence or absence of metabolic health, is a risk factor for CKD.

Safety and efficacy of sequential treatments for postmenopausal osteoporosis: a network meta-analysis of randomised controlled trials.

Background: The sequential anti-osteoporotic treatment for women with postmenopausal osteoporosis (PMO) is important, but the order in which different types of drugs are used is confusing and controversial. Therefore, we performed a network meta-analysis to compare the efficacy and safety of available sequential treatments to explore the most efficacious strategy for long-term management of osteoporosis. Methods: In this network meta-analysis, we searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov from inception to September 19, 2023 to identify randomised controlled trials comparing sequential treatments for women with PMO. The identified trials were screened by reading the title and abstract, and only randomised clinical trials involving sequential anti-osteoporotic treatments and reported relevant outcomes for PMO were included. The main outcomes included vertebral fracture risk, the percentage change in bone mineral density (BMD) in different body parts, and all safety indicators in the stage after switching treatment. A frequentist network meta-analysis was performed using the multivariate random effects method and evaluated using the surface under the cumulative ranking curve (SUCRA). Certainty of evidence was assessed using the Confidence in the Network Meta-Analysis (CINeMA) framework. This study is registered with PROSPERO: CRD42022360236. Findings: A total of 19 trials comprising 18,416 participants were included in the study. Five different sequential treatments were investigated as the main interventions and compared to the corresponding control groups. The intervention groups in this study comprised the following treatment switch protocols: switching from an anabolic agent (AB) to an anti-resorptive agent (AR) (ABtAR), transitioning from one AR to another AR (ARtAAR), shifting from an AR to an AB (ARtAB), switching from an AB to a combined treatment of AB and AR (ABtC), and transitioning from an AR to a combined treatment (ARtC). A significant reduction in the incidence of vertebral fractures was observed in ARtC, ABtAR and ARtAB in the second stage, and ARtC had the lowest incidence with 81.5% SUCRA. ARtAAR and ABtAR were two effective strategies for preventing fractures and improving BMD in other body parts. Especially, ARtAAR could improve total hip BMD with the highest 96.1% SUCRA, and ABtAR could decrease the risk of total fractures with the highest 94.3% SUCRA. Almost no difference was observed in safety outcomes in other comparisons. Interpretation: Our findings suggested that the ARtAAR and ABtAR strategy are the effective and safe sequential treatment for preventing fracture and improving BMD for PMO. ARtC is more effective in preventing vertebral fractures. Funding: The National Natural Science Foundation of China (82170900, 81970762), the Hunan Administration of Traditional Chinese Medicine, and the Hunan Province High-level Health Talents "225" Project.

[Effects of Mulching and Application of Organic and Chemical Fertilizer on Greenhouse Gas Emission and Water and Nitrogen Use in Summer Maize Farmland].

To explore the effects of mulching and the application of organic and chemical fertilizer on N2O, CO2, and CH4 emission; maize yield; water use efficiency (WUE); and nitrogen fertilizer use efficiency under the conditions of the same nitrogen fertilizer input in summer maize farmland, an experiment was conducted in the Guanzhong Plain of China. In this experiment, the two main experimental factors were mulching (M) and no-mulching, and the secondary experimental factors included no fertilizer application (CK), organic fertilizer substituting chemical fertilizer at 0% (T0, 0.00 kg·hm-2 organic fertilizer and 225.00 kg·hm-2 chemical fertilizer), 25% (T25, 56.25 kg·hm-2 organic fertilizer and 168.75 kg·hm-2 chemical fertilizer), 50% (T50, 112.50 kg·hm-2 organic fertilizer and 112.50 kg·hm-2 chemical fertilizer), 75% (T75, 168.75 kg·hm-2 organic fertilizer and 56.25 kg·hm-2 chemical fertilizer), and 100% (T100, 225.00 kg·hm-2 organic fertilizer and 0.00 kg·hm-2 chemical fertilizer), for a total of 12 treatments. The results showed as follows:1 both mulching and fertilizer application (with or without mulching) factors significantly increased soil N2O and CO2 emissions and reduced soil uptake of CH4(P<0.05). Compared to chemical fertilizer treatments, the organic fertilizer treatments reduced soil N2O emission by 11.8% to 52.6% and 14.1% to 68.0% and increased soil CO2 emission by 5.1% to 24.1% and 15.1% to 48.7% under mulching and no-mulching conditions, respectively (P<0.05). Compared to that under no-mulching, the global warming potential (GWP) under mulching increased by 140.7% to 206.6%. Compared to that in the CK treatment, the GWP of fertilized treatments increased by 36.6% to 67.6% and 31.2% to 89.1% under mulching and no-mulching conditions (P<0.05), respectively. Combined with the yield factor, the greenhouse gas intensity (GHGI) under the mulching condition increased by 103.4% to 166.2% compared to that under the no-mulching condition. Therefore, GHG emissions could be reduced by increasing yields. 2 The mulching treatments increased maize yield by 8.4% to 22.4% and WUE by 4.8% to 24.9% (P<0.05). Fertilizer application significantly increased maize yield and WUE. The organic fertilizer treatments increased yield by 2.6% to 8.5% and WUE 13.5% to 23.2% under the mulching condition compared to that in the MT0 treatment and increased yield by 3.9% to 14.3% and WUE 4.5% to 18.2% under the no-mulching condition compared to that in the T0 treatment. 3 In the 0-40 cm soil layer, the total nitrogen content of mulching treatments was increased by 2.4% to 24.7% compared with that of the no-mulching treatments. Fertilizer application treatments increased the total nitrogen content by 18.1% to 48.9% and 15.4% to 49.7% under the mulching and no-mulching conditions, respectively. Mulching and fertilizer application promoted nitrogen accumulation and nitrogen fertilizer use efficiency in maize plants (P<0.05). Compared to that in chemical fertilizer treatments, the organic fertilizer treatments increased nitrogen fertilizer use efficiency by 2.6% to 8.5% and 3.9% to 14.3% under mulching and no-mulching conditions, respectively. Combining ecological and economic benefits, the MT50 under mulching conditions and T75 under no-mulching conditions can be recommended as planting models to guarantee stable yield and achieve green and sustainable agricultural production.

Tai Chi as a complementary exercise for pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomised controlled trial.

OBJECTIVES: With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. DESIGN AND SETTING: This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. RESULTS: A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George's Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI -8.99 to 8.99), -9.28 (95 % CI -13.96 to -4.60), -10.19 (95 % CI -13.72 to -6.67), and -16.75 (95 % CI -20.25 to -13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P < 0.001). The remarkable effect of TBRS-TC exercise in improving the quality of life maintained until the end of the community- or home-based rehabilitation training (P < 0.001). Besides, a statistically better effect with the TBRS-TC exercise was also observed in the outcomes regarding exercise capacity, pulmonary function, symptom burden, and systemic inflammation after the whole process of 12-month integrative PR exercise programme. CONCLUSIONS: Based on the results, a novel integrated exercise modality combining Tai Chi and conventional pulmonary rehabilitation was developed. It might contribute to more positive effects in patients with stable COPD. REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-15006874) prior to commencing recruitment.

Cardio-cerebrovascular Outcomes in MODY, Type 1 Diabetes, and Type 2 Diabetes: A Prospective Cohort Study.

CONTEXT: Cardio-cerebrovascular events are severe complications of diabetes. OBJECTIVE: We aim to compare the incident risk of cardio-cerebrovascular events in maturity onset diabetes of the young (MODY), type 1 diabetes, and type 2 diabetes. METHODS: Type 1 diabetes, type 2 diabetes, and MODY were diagnosed by whole exome sequencing. The primary endpoint was the occurrence of the first major adverse cardiovascular event (MACE), including acute myocardial infarction, heart failure, stroke, unstable angina pectoris, and cardio-cerebrovascular-related mortality. Cox proportional hazards models were applied and adjusted to calculate hazard ratios (HRs) and 95% CIs for the incident risk of MACE in type 1 diabetes, type 2 diabetes, MODY, and MODY subgroups compared with people without diabetes (control group). RESULTS: Type 1 diabetes, type 2 diabetes, and MODY accounted for 2.7%, 68.1%, and 11.4% of 26 198 participants with diabetes from UK Biobank. During a median follow-up of 13 years, 1028 MACEs occurred in the control group, contrasting with 70 events in patients with type 1 diabetes (HR 2.15, 95% CI 1.69-2.74, P < .05), 5020 events in patients with type 2 diabetes (HR 7.02, 95% CI 6.56-7.51, P < .05), and 717 events in MODY (HR 5.79, 95% CI 5.26-6.37, P < .05). The hazard of MACE in HNF1B-MODY was highest among MODY subgroups (HR 11.00, 95% CI 5.47-22.00, P = 1.5 × 10-11). CONCLUSION: MODY diagnosed by genetic analysis represents higher prevalence than the clinical diagnosis in UK Biobank. The risk of incident cardio-cerebrovascular events in MODY ranks between type 1 diabetes and type 2 diabetes.

Hereditary severe insulin resistance syndrome: Pathogenesis, pathophysiology, and clinical management.

Severe insulin resistance has been linked to some of the most globally prevalent disorders, such as diabetes mellitus, nonalcoholic fatty liver disease, polycystic ovarian syndrome, and hypertension. Hereditary severe insulin resistance syndrome (H-SIRS) is a rare disorder classified into four principal categories: primary insulin receptor defects, lipodystrophies, complex syndromes, and obesity-related H-SIRS. Genes such as INSR, AKT2, TBC1D4, AGPAT2, BSCL2, CAV1, PTRF, LMNA, PPARG, PLIN1, CIDEC, LIPE, PCYT1A, MC4R, LEP, POMC, SH2B1, RECQL2, RECQL3, ALMS1, PCNT, ZMPSTE24, PIK3R1, and POLD1 have been linked to H-SIRS. Its clinical features include insulin resistance, hyperglycemia, hyperandrogenism, severe dyslipidemia, fatty liver, abnormal topography of adipose tissue, and low serum leptin and adiponectin levels. Diagnosis of H-SIRS is based on the presence of typical clinical features associated with the various H-SIRS forms and the identification of mutations in H-SIRS-linked genes by genetic testing. Diet therapy, insulin sensitization, exogenous insulin therapy, and leptin replacement therapy have widely been adopted to manage H-SIRS. The rarity of H-SIRS, its highly variable clinical presentation, refusal to be tested for genetic mutations by patients' family members who are not severely sick, unavailability of genetic testing, and testing expenses contribute to the delayed or underdiagnoses of H-SIRS. Early diagnosis facilitates early management of the condition, which results in improved glycemic control and delayed onset of diabetes and other complications related to severe insulin resistance. The use of updated genetic sequencing technologies is recommended, and long-term studies are required for genotype-phenotype differentiation and formulation of diagnostic and treatment protocols.

Chronic renal failure impacts the expression of ghrelin and its receptor in hypothalamus and hippocampus.

BACKGROUND/AIMS: Ghrelin plays a central role in the regulation of gastrointestinal (GI) motility. This study aimed to investigate the expression of ghrelin and growth hormone secretagogue receptor (GHSR) in the central nervous system of rats with chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 20 g, n = 24) were treated by 5/6 nephrectomy to construct CRF model. As their plasma creatinine concentration and blood urea nitrogen were maintained more than double the normal level for 2 weeks, they were killed for assessing the expression of ghrelin and GHSR in hypothalamus and hippocampus using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). The rats (male, 180 ± 20 g, n = 24) treated by Sham operation served as a control. One-way analysis of variance and Student-Newman-Keuls q test were used to analyze group difference and a p-value of <0.05 was considered as statistically significant. RESULTS: Compared with the controls, the ghrelin and GHSR expression was obviously increased in the hippocampus (p < 0.05) but decreased in the hypothalamus of rats with CRF (p < 0.05). CONCLUSIONS: CRF was found to impact the expression of ghrelin and GHSR in hypothalamus and hippocampus. This might be associated with the CRF-induced GI motility dysfunction.

Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus-a systematic review and meta-analysis of randomized control trials.

Clinical trials have investigated the weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in adults with obesity without diabetes mellitus, but results for weight loss efficacy were varied. We aimed to provide an up-to-date systematic review and meta-analysis for overall weight loss effect of GLP-1 RA in adults with obesity and overweight without diabetes mellitus. We retrieved eligible randomized control trials that assessed the weight loss effect of GLP-1 RA in adults (≥18 years old) without type 1/type 2 diabetes up to September 30, 2021, using Pubmed and Embase. Of 36 clinical trials assessed for eligibility, 12 trials were included, with a combined total of 11,459 participants. Compared with control groups, a more significant weight loss was seen in GLP-1 RA groups with an overall mean difference of -7.1 kg (95% CI -9.2 to -5.0) (I2  = 99%). The overall analysis results showed that GLP-1 RA improved glycemic control without increasing the risk of hypoglycemic events. Better control of blood pressure and plasma levels of LDL, HDL, and triglycerides was seen with GLP-1 RA treatment. Subgroup analysis showed greater treatment effect of semaglutide than liraglutide. Vomiting, nausea, dyspepsia, diarrhea, constipation, and abdominal pain were GLP-1 RA-associated common adverse effects.

Diosgenin exerts an antihypertensive effect in spontaneously hypertensive rats via gut-brain communication.

Gut microbiota is well-established to regulate host blood pressure. Diosgenin is a natural steroid sapogenin with documented anti-inflammatory, antioxidant and antihypertensive properties. We aimed to investigate whether the antihypertensive effects of diosgenin are mediated by the microbiota-gut-brain axis in spontaneously hypertensive rats (SHR). 15-Week-old male Wistar Kyoto rats (WKY) and age-matched SHR were randomly distributed into three groups: WKY, SHR treated with a vehicle, and SHR treated with diosgenin (100 mg kg-1). Our results showed that diosgenin prevented elevated systolic blood pressure (SBP) and ameliorated cardiac hypertrophy in SHR. Moreover, the gut microbiota composition and intestinal integrity were improved. Furthermore, increased butyrate-producing bacteria and plasma butyrate and decreased plasma lipopolysaccharides were observed in SHR treated with diosgenin. These findings were associated with reduced microglial activation and neuroinflammation in the paraventricular nucleus. Our findings suggest that diosgenin attenuates hypertension by reshaping the gut microbiota and improving the gut-brain axis.

[(E)-N'-(5-Chloro-2-oxidobenzyl-idene-κO)-3,4,5-trimeth-oxy-benzohydrazidato-κN',O](pyridine-κN)copper(II).

In the title compound, [Cu(C(17)H(15)ClN(2)O(5))(C(5)H(5)N)], the Cu(II) atom is coordinated by one N atom and two O atoms from an anionic salicyl-aldehyde benzoyl-hydrazone ligand and one pyridine N atom in a distorted square-planar geometry. The bonds displays the usual elongation with mean Cu-O and Cu-N bond lengths of 1.926 and 1.976 Å, respectively. The pyridine ring makes dihedral angles of 26.12 (13) and 11.08 (12)°, respectively, with the trimeth-oxy-phenyl and phenolate rings, which make a dihedral angle of 16.05 (12)° with one another.

[Tanreqing Injection for community-acquired pneumonia: a systematic review of randomized evidence].

OBJECTIVE: To evaluate the efficacy and safety of Tanreqing Injection, a compound traditional Chinese herbal medicine, for community-acquired pneumonia. METHODS: Literatures about randomized controlled trials of Tanreqing Injection for community-acquired pneumonia were reviewed. Related literatures were selected and analyzed according to different treatment strategies of the trials. The methodological quality of the trials was assessed by the Jadad scale, and evaluation was performed. RESULTS: Twelve randomized controlled trials meeting the inclusion criteria were selected and reviewed. As Tanreqing combined group (Tanreqing Injection plus antibiotics and basic therapy) was compared with antibiotics group (antibiotics plus basic therapy), the meta-analysis indicated that the relative risk (RR) for the total cure rate was 1.51, and 95% confidence interval (CI) was [1.29, 1.77]; RR for the total obvious effect rate was 1.31,ls and 95% CI was [1.20,1.43]; RR for the effective rate was 1.17, and 95% CI was [1.11, 1.23]. The weighted mean difference (WMD) in disappearance time of fever between the two groups was -1.24, and 95% CI was [-1.71, -0.76]. The RR values between the two groups for the total obvious effect rate of cough and expectoration were 1.42 and 1.27, and 95% CIs were [1.16, 1.74] and [1.04, 1.55] respectively. The RR values between the two groups in absorption of chest X-ray shadow and neutrophil number were 1.19, 1.10 and 95% CIs were [1.09, 1.30], [1.03, 1.17] respectively. The differences were all statistically significant. Serious systematic adverse reactions had not been reported in the trials. CONCLUSION: The effect of combined therapy with Tanreqing Injection plus antibiotics and basic therapy is better than that of antibiotics plus basic therapy. Tanreqing Injection can improve the symptoms of cough and expectoration, shorten the fever time and facilitate the absorption of chest X-ray shadow, without any significant adverse reactions. However, further high-quality trials are needed.

[Chinese medicine for acute upper respiratory tract infection: a systematic review of randomized controlled trials].

OBJECTIVE: To evaluate the efficacy and safety of new drugs of traditional Chinese medicine (TCM) for acute upper respiratory tract infection (common cold). METHODS: Reports regarding randomized controlled trials of Chinese medicine for common cold were reviewed. Related reports were selected and the methodological quality of the trials was assessed by the Jadad scale. Meanwhile, the stratified analysis was made according to different TCM syndrome types of common cold. RESULTS: Thirteen randomized controlled trials consistent with the inclusion criteria were selected and reviewed. As TCM treatment group was compared with control group, the meta analysis indicated that the relative risk (RR) for obviously effective rate was 1.10, and the 95% confidence interval (CI) was [1.05, 1.16]; the weighted mean difference (WMD) of the onset time of lowering body temperature was -1.70, and the 95% CI was [-2.76, -0.65]. There were significant differences in the above evaluation indexes between the two groups (P=0.000 2, P=0.002). The WMD of disappearing time of fever was -1.32, and the 95% CI was [-3.14, 0.49], while there was no significant difference between the two groups (P=0.15). As the common cold patients with wind-heat syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.11, the 95% CI was [1.05, 1.19], and there was significant difference between the two groups (P=0.000 7). As the common cold patients with wind-cold syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.07, the 95% CI was [0.99, 1.16], and there was no significant difference between the two groups (P=0.10). Serious adverse reactions had not been reported in the trials. CONCLUSION: TCM new drugs developed in recent years for preventing and treating common cold have better therapeutic effects than the old ones. They can accelerate the onset time of lowering body temperature and improve the symptoms of common cold without any significant adverse reactions. Because of lacking of placebo-controlled and blank-controlled studies, further high-quality trials are still needed.