CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness.

Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10+GPR77+ CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10+GPR77+ CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10+GPR77+ CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10+GPR77+ CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors.

Single-cell transcriptome analyses reveal critical roles of RNA splicing during leukemia progression.

Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Here, we performed serial single-cell transcriptome analyses of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven acute myeloid leukemia (AML) model in mice, which represented the transformation course in patients. We found that the Myc targets were gradually up-regulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for hematopoietic stem and progenitor cells (HSPCs) to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aa1hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 4 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134ß promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.

Association between Whole Grain Intake and Chronic Kidney Disease.

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Associations between whole grains intake and new-onset hypertension: a prospective cohort study.

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

Long-term exposure to air pollutants and new-onset migraine: A large prospective cohort study.

BACKGROUNDS: Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large prospective cohort study was to explore these links. METHODS: A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis. RESULTS: During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01-1.06, P = 0.009), PM10 (HR: 1.07, 95% CI: 1.04-1.10, P < 0.001), NO2 (HR: 1.10, 95% CI: 1.07-1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01-1.07, P = 0.005) in the main model. The air pollution score showed a doseresponse association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04-1.19, P = 0.002) and 1.17 (95% CI: 1.09-1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001). CONCLUSION: Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

The mediating effect of coping styles between emergency capacity and mental workload among clinical nurses: A cross-sectional study.

AIMS: This study aimed to examine the relationship between emergency capacity, coping styles, and mental workload among nurses. BACKGROUND: Emergency capacity, coping styles, and mental workload are all variables associated with work. Identifying the relationship between these variables can facilitate administrators to implement tailored and effective intervention strategies to improve individual performance, quality of care, and medical safety. METHODS: A quantitative cross-sectional study was carried out to investigate 605 Chinese clinical nurses in seven tertiary hospitals by using personal information form, emergency capacity scale for nurses, simplified coping skill questionnaire, and the NASA-Task Load Index. RESULTS: Emergency capacity and mental workload were found at moderate levels. The multiple linear regression model suggested that spinsterhood, no children, high workload, always anxiety or nervousness, and lower monthly income were the influencing factors of mental workload. Positive coping style was positively correlated with emergency capacity and negatively correlated with mental workload. Negative coping style was negatively related to emergency capacity and positively related to mental workload. Additionally, coping styles played a partial mediating role in the relationship between emergency capacity and mental workload through constructing a structural equation model, but the effects of positive coping style and negative coping style are opposite. CONCLUSION: Our results showed that coping styles played a mediating role in the relationship between emergency capacity and mental workload. Managers can alleviate the mental workload of nurses by cultivating positive coping styles and improving emergency capacity. IMPLICATIONS FOR NURSING AND NURSING POLICY: Mental workload of nurses deserves more attention in medical institutions. The results of our study provide evidence for improving employee health, promoting positive behaviors, and optimizing organizational management. Nursing managers should take feasible measures to fulfill nurses' needs for emergency capacity and coping strategies to alleviate nurses' mental workload, so as to stimulate their intrinsic motivation and positive organizational behavior.

Deoxyshikonin inhibited rotavirus replication by regulating autophagy and oxidative stress through SIRT1/FoxO1/Rab7 axis.

BACKGROUND: Rotavirus (RV) is a double-stranded RNA virus. RV prevention and treatment remain a major public health problem due to the lack of clinically specific drugs. Deoxyshikonin is a natural compound isolated from the root of Lithospermum erythrorhizon and one of the shikonin derivatives which owns remarkable therapeutic effects on multiple diseases. The purpose of this research was to inquire Deoxyshikonin's role and mechanism in RV infection. METHODS: Deoxyshikonin's function in RV was estimated using Cell Counting Kit-8 analysis, cytopathic effect inhibition assay, virus titer determination, quantitative real-time PCR, enzyme linked-immunosorbent assay, Western blot, immunofluorescence, and glutathione levels detection. Also, Deoxyshikonin's mechanism in RV was appraised with Western blot, virus titer determination, and glutathione levels detection. Moreover, Deoxyshikonin's function in RV in vivo was determined using animal models, and diarrhea score analysis. RESULTS: Deoxyshikonin owned anti-RV activity and repressed RV replication in Caco-2 cells. Furthermore, Deoxyshikonin reduced autophagy and oxidative stress caused by RV. Mechanistically, Deoxyshikonin induced low protein levels of SIRT1, ac-Foxo1, Rab7, VP6, low levels of RV titers, low autophagy and oxidative stress. SIRT1 overexpression abolished the effects of Deoxyshikonin on RV-treated Caco-2 cells. Meanwhile, in vivo research affirmed that Deoxyshikonin also possessed anti-RV function, and this was reflected in increased survival rate, body weight, GSH levels, and decreased diarrhea score, RV virus antigen, LC-3II/LC3-I. CONCLUSION: Deoxyshikonin reduced RV replication through mediating autophagy and oxidative stress via SIRT1/FoxO1/Rab7 pathway.

Pulsed Electromagnetic Fields Protect Against Brain Ischemia by Modulating the Astrocytic Cholinergic Anti-inflammatory Pathway.

Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.

MicroRNA-194-3p impacts autophagy and represses rotavirus replication via targeting silent information regulator 1.

BACKGROUND: Rotavirus (RV) is the main cause of serious diarrhea in infants and young children worldwide. Numerous studies have demonstrated that RV use host cell mechanisms to motivate their own stabilization and multiplication by degrading, enhancing, or hijacking microRNAs (miRNAs). Therefore, exploring the molecular mechanisms by which miRNAs motivate or restrain RV replication by controlling different biological processes, including autophagy, will help to better understand the pathogenesis of RV development. This study mainly explored the effect of miR-194-3p on autophagy after RV infection and its underlying mechanism of the regulation of RV replication. METHODS: Caco-2 cells were infected with RV and used to measure the expression levels of miR-194-3p and silent information regulator 1 (SIRT1). After transfection with plasmids and RV infection, viral structural proteins, RV titer, cell viability, and autophagy-linked proteins were tested. The degree of acetylation of p53 was further investigated. A RV-infected neonatal mouse model was constructed in vivo and was evaluated for diarrhea symptoms and lipid droplet formation. RESULTS: The results showed that miR-194-3p was reduced but SIRT1 was elevated after RV infection. Elevation of miR-194-3p or repression of SIRT1 inhibited RV replication through the regulation of autophagy. The overexpression of SIRT1 reversed the effects of miR-194-3p on RV replication. The upregulation of miR-194-3p or the downregulation of SIRT1 repressed RV replication in vivo. MiR-194-3p targeted SIRT1 to decrease p53 acetylation. CONCLUSION: These results were used to determine the mechanism of miR-194-3p in RV replication, and identified a novel therapeutic small RNA molecule that can be used against RV.

Disrupted topological organization of functional brain networks is associated with cognitive impairment in hypertension patients: a resting-state fMRI study.

PURPOSE: To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores. METHODS: Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized. RESULTS: HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network. CONCLUSION: This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.

Prognostic implication of lactic dehydrogenase-to-albumin ratio in critically ill patients with acute kidney injury.

BACKGROUND: No studies have been published on the correlation between lactic dehydrogenase-to-albumin ratio (LAR) and poor prognosis of acute kidney injury (AKI) patients, warranting further research. This analysis sought to investigate the prognostic implication of LAR in critically ill patients with AKI. METHODS: The present study enrolled 11,046 and 5180 adults with AKI from the Medical Information Mart for Intensive Care III (MIMIC III) and MIMIC IV, respectively. Data from MIMIC IV were identified as the training cohort, and those from MIMIC III were identified as the validation cohort. We applied multivariate regression analysis to identify the link between LAR and all-cause mortality. Restricted cubic spline (RCS) was conducted to figure out the correlation between LAR and in-hospital mortality. Furthermore, we carried out stratification analyses to examine if the effects of LAR on in-hospital mortality were consistent across various subclasses. RESULTS: The level of LAR was remarkably higher in the in-hospital non-survivor group (p < 0.001). Furthermore, the increased LAR group presented a remarkably higher rate of in-hospital mortality at AKI stages 1, 2, and 3 compared with the decreased LAR group (all p < 0.001). Multivariate regression analyses exhibited the independent prognostic significance of LAR for all-cause mortality (all p < 0.001). MIMIC III observed concordant results. RCS indicated a non-linear correlation between LAR and in-hospital death (P for non-linearity < 0.001). The relationship between LAR and in-hospital mortality was still significant in patients with various subclasses. CONCLUSIONS: Elevated LAR at admission is a prognostic risk factor for critically ill patients with AKI.

Differentiating tumour progression from pseudoprogression in glioblastoma patients: a monoexponential, biexponential, and stretched-exponential model-based DWI study.

BACKGROUND: To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients. METHODS: Forty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements. RESULTS: The values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88). CONCLUSIONS: Multi-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.

Comprehensive Evolution and Expression anaLysis of PHOSPHATE 1 Gene Family in Allotetraploid Brassica napus and Its Diploid Ancestors.

The members of PHOSPHATE 1 (PHO1) family play important roles in plant phosphate (Pi) transport and adaptation to Pi deficiency. The functions of PHO1 family proteins have been reported in several plant species, with the exception of Brassica species. Here, we identified 23, 23, and 44 putative PHO1 family genes in Brassica rapa, Brassica oleracea, and Brassica napus by whole genome analysis, respectively. The phylogenetic analysis divided PHO1 family proteins into eight groups, which represented the orthologous relationships among PHO1 members. The gene structure and the conserved motif analysis indicated that the most PHO1 family genes had similar gene structures and the PHO1 proteins shared mutual conserved motifs. The chromosome distribution analysis showed that the majority of BnPHO1 family genes distributed analogously at chromosomes with BrPHO1 and BoPHO1 family genes. The data showed that PHO1 family genes were highly conserved during evolution from diploid to tetraploid. Furthermore, the expression analysis showed that PHO1 family genes had different expression patterns in plant tissues, suggesting the diversity of gene functions in Brassica species. Meanwhile, the expression analysis also revealed that some PHO1 family genes were significantly responsive to Pi deficiency, suggesting that PHO1 family genes play critical roles in Pi uptake and homeostasis under low Pi stress. Altogether, the characteristics of PHO1 family genes provide a reliable groundwork for further dissecting their functions in Brassica species.

Clinical evidence of dietary supplementation with sesame on cardiovascular risk factors: An updated meta-analysis of randomized controlled trials.

The present analysis was to summarize the evidence of the effects of sesame and its derivatives supplementation on cardiovascular disease (CVD) risk factors by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases were searched from their inception to July 2020. Two investigators independently assessed articles for inclusion, extracted data, and statistical analysis. The quality of included articles was assessed according to the Cochrane risk of bias tool. Major outcomes were synthesized using a random effect model and presented as weighted mean difference and 95% confidence interval. Heterogeneity, subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted. The GRADE approach was used to evaluate the quality of evidence. Overall, 16 trials involving 908 participants were included for statistical pooling. Compared with the control group, sesame intake significantly decreased the levels of total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body weight, body mass index, hip circumference, and waist circumference (P < 0.05). These results were stable in sensitivity analysis, and no significant publication bias was detected. Our findings provided evidence that sesame consumption may reduce the risk of CVD by improving blood lipids, blood pressure, and body weight management. Further large-scale, well-designed RCTs are required to confirm these results.

Predictive Value of the Peripheral Blood Parameters for Preeclampsia.

BACKGROUND: Excessive systemic inflammation plays a vital role in pathophysiology of preeclampsia (PE). The aim is to clarify the predictive value of the peripheral blood parameters including white blood cell (WBC), neutrophils, lymphocyte, monocyte, platelet count, mean platelet volume (MPV), plateletcrit, platelet distribution width (PDW), platelet-large cell ratio (PLCR), and the ratio value for PE. METHODS: This retrospective study enrolled 170 PE patients, 123 healthy control pregnant women, and 122 non-pregnant women. When pregnant women were admitted to the hospital for delivery, peripheral complete blood cell count was detected by an automatic blood cell analyzer. Clinical signs and demographic characteristics were recorded. The receiver operating characteristic (ROC) curve was used to determine the cutoff value and analyze the predictive significances for PE. Furthermore, the risk factors of PE were tested by univariate and stratified analyses. RESULTS: This study showed that WBC, neutrophil count, neutrophil percentage, NLR, NMR, and PLR# were significantly increased in PE patients as compared with pregnant control patients (p < 0.001), whereas lymphocyte percentage, monocyte percentage, and PNR were decreased. In addition, there was no significant difference in the rest of the peripheral blood parameters between women with and without PE. The ROC curve result revealed that WBC and neutrophil count had a higher AUC value than the rest of peripheral blood variables. WBC and neutrophil count are positively correlated MAP. Moreover, the WBC and neutrophil count were indicated as independent risk factors for the development of PE. CONCLUSIONS: This study clarifies that peripheral blood parameters of WBC and neutrophil count have good applied value with high sensitivity and specificity in predicting the development of PE and are also independent risk factors for the development of PE.

Clinical evidence of the effects of carnitine supplementation on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Several clinical trials have investigated the influence of carnitine on metabolic variables in PCOS, but have yielded conflicting results. This study aimed to summarize the clinical evidence of the effects of carnitine on weight management, glycemic and serum lipids controls in women with PCOS by conducting a meta-analysis of randomized control trials (RCTs). PubMed, Embase, Web of Sciences, Scopus, and the CENTRAL database were searched from inception to March 2021 for eligible articles. Study selection and assessment of quality were conducted independently by two investigators. Effect sizes for each outcome were reported with the weighted mean differences (WMDs) and 95% confidence intervals (CIs). The statistical heterogeneity of the included clinical trials was tested using the I2 statistic. Six studies with 672 PCOS participants were included for meta-analysis. Our results revealed that carnitine supplements significantly decreased total cholesterol, low-density lipoprotein-cholesterol, triglycerides, body weight, body mass index, hip circumference, and waist circumference (All p < .05). In addition, carnitine intervention also improved the levels of high-density lipoprotein cholesterol. However, no significant changes were seen in glucose homeostasis parameters. These results were stable after sensitivity analysis, and no significant publication biases were detected. Based on current evidence, carnitine supplementation in women with PCOS had beneficial effects on weight loss and lipid profiles. Further large-scale, well-designed RCTs are required to confirm these results.

The diagnostic model for early detection of gestational diabetes mellitus and gestational diabetic nephropathy.

BACKGROUND: Gestational diabetes mellitus (GDM) and gestational diabetic nephropathy (GDN) have become an increasingly serious problem worldwide, which can cause a large number of adverse pregnancy consequences for mothers and infants. However, the diagnosis of GDM and GDN remains a challenge due to the lack of optimal biomarkers, and the examination has high requirements for patient compliance. We aimed to establish a simple early diagnostic model for GDM and GDN. METHODS: We recruited 50 healthy pregnant (HP), 99 GDM patients, 99 GDN patients at Daping Hospital. Renal function indicators and blood cell indicators were collected for all patients. RESULTS: Compared with HP, GDM, and GDN patients exhibited significantly higher urea/creatinine ratio and NEU. The diagnostic model1 based on the combination of urea/creatinine ratio and NEU was built using logistic regression. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the diagnostic model was 0.77 (0.7, 0.84) in distinguishing GDM from HP, and the AUC of the diagnostic model was 0.94 (0.9, 0.97) in distinguishing GDN from HP. Meanwhile, the diagnostic model2 based on the combination of ß2-mG, PLT, and NEU in GDM and GDN patients was built using logistic regression, and the area under the ROC curve (AUC ROC) was 0.79 (0.73, 0.85), which was larger than the individual biomarker AUC. CONCLUSION: Our study demonstrated that the diagnostic model established by the combination of renal function indicators and blood cell indicators could facilitate the differential diagnosis of GDM and GDN patients.

Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of Bmp7 and Ctgf.

RATIONALE: Pathogenic variations in the lamin gene (LMNA) cause familial dilated cardiomyopathy (DCM). LMNA insufficiency caused by LMNA pathogenic variants is believed to be the basic mechanism underpinning LMNA-related DCM. OBJECTIVE: To assess whether silencing of cardiac Lmna causes DCM and investigate the role of Yin Yang 1 (Yy1) in suppressing Lmna DCM. METHODS AND RESULTS: We developed a Lmna DCM mouse model induced by cardiac-specific Lmna short hairpin RNA. Silencing of cardiac Lmna induced DCM with associated cardiac fibrosis and inflammation. We demonstrated that upregulation of Yy1 suppressed Lmna DCM and cardiac fibrosis by inducing Bmp7 expression and preventing upregulation of Ctgf. Knockdown of upregulated Bmp7 attenuated the suppressive effect of Yy1 on DCM and cardiac fibrosis. However, upregulation of Bmp7 alone was not sufficient to suppress DCM and cardiac fibrosis. Importantly, upregulation of Bmp7 together with Ctgf silencing significantly suppressed DCM and cardiac fibrosis. Mechanistically, upregulation of Yy1 regulated Bmp7 and Ctgf reporter activities and modulated Bmp7 and Ctgf gene expression in cardiomyocytes. Downregulation of Ctgf inhibited TGF-ß (transforming growth factor-ß)/Smad signaling in DCM hearts. Regulation of both Bmp7 and Ctgf further suppressed TGFß/Smad signaling. In addition, co-modulation of Bmp7 and Ctgf reduced CD3+ T cell numbers in DCM hearts. CONCLUSIONS: Our findings demonstrate that upregulation of Yy1 or co-modulation of Bmp7 and Ctgf offer novel therapeutic strategies for the treatment of DCM caused by LMNA insufficiency.

LncRNA FAM230B Promotes Gastric Cancer Growth and Metastasis by Regulating the miR-27a-5p/TOP2A Axis.

AIM: Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC). METHOD: The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells. RESULTS: We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression. CONCLUSION: Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.