Prevalence and risk factors of MAFLD and its metabolic comorbidities in community-based adults in China: A cross-sectional study.

AIMS: There is a growing interest in the co-management of metabolic dysfunction-associated fatty liver disease (MAFLD) and its metabolic comorbidities. However, there is insufficient epidemiological data regarding MAFLD and its metabolic comorbidities in China. This study aims to investigate the prevalence and risk factors of MAFLD and its metabolic comorbidities. METHODS: 9171 participants were recruited in this cross-sectional study, utilizing a multistage, stratified sampling method. All participants underwent a comprehensive assessment. The diagnosis of MAFLD was based on vibration-controlled transient elastography (VCTE). The prevalence of MAFLD and its metabolic comorbidities was calculated. Binary and ordinary logistic regressions were conducted. RESULTS: The overall weighted prevalence of MAFLD was 21.18%. Of the 2081 adults with MAFLD, 1866 (89.67%) had more than one metabolic comorbidity, and only 215 (10.33%) did not have comorbidity. Among the population with MAFLD, the prevalence of dyslipidemia, hypertension, hyperuricemia, and diabetes was 67.47%, 43.73%, 39.10%, and 33.88%, respectively. Advanced age, male gender, overweight/obesity, excessive alcohol consumption, and elevated HOMA-IR levels were positively correlated with the number of MAFLD-related metabolic comorbidities. CONCLUSIONS: A significant proportion of individuals diagnosed with MAFLD presented with metabolic comorbidities. Therefore, engaging in the co-management of MAFLD and its metabolic comorbidities is imperative.

Application of membrane separation technology in the purification of pharmaceutical components.

Traditional Chineae medicine (TCM) is often composed of a variety of natural medicines. Its composition is complex, and many of its components can not be analyzed and identified. The first step in the rational application of TCM is to successfully separate the effective components which is also a great inspiration for the development of new drugs. Among the many separation technologies of TCM, the traditional heating concentration separation technology has high energy consumption and low efficiency. As a new separation technology, membrane separation technology has the characteristics of simple operation, high efficiency, environment-friendly and so on. The separation effect of high molecular weight difference solution is better. The applications of several main membrane separation technologies such as microfiltration, nanofiltration, ultrafiltration and reverse osmosis are reviewed, the methods of restoring membrane flux after membrane fouling are discussed, and their large-scale industrial applications in the future are prospected and summarized.

Associations of thyroid feedback quantile-based index with diabetes in euthyroid adults in the United States and China.

BACKGROUND: We aimed to investigate the associations between thyroid hormone sensitivity indices and diabetes in euthyroid adults in the United States and China. METHODS: 2296 euthyroid adults from the NHANES in the United States and 8319 euthyroid adults from the SPEED-Shunde in China were involved. The thyroid sensitivity indices, namely TFQIFT4 and TFQIFT3, were calculated. Multivariable logistic regression, restricted cubic spline analysis, and general ordinal logit regression were utilized. RESULTS: In the NHANES, compared with participants in quartile 1st (Q1), those in Q4 of TFQIFT3 (OR 2.12, 95% CI (1.18, 3.81)) and those in Q3 of TFQIFT4 (OR 2.31, 95% CI (1.18, 4.53)) (both P for trend < 0.05) were associated with a greater prevalence of diabetes. In the SPEED-Shunde, compared with participants in Q1, those in Q4 of TFQIFT3 had a greater prevalence of diabetes (OR 1.36, 95% CI (1.11, 1.66) (P for trend < 0.05), while no significant associations between TFQIFT4 and diabetes were found. CONCLUSIONS: TFQIFT3 was associated with a higher prevalence of diabetes both in the United States and China. However, TFQIFT4 was only associated with a higher prevalence of diabetes in the United States, not in China. Further prospective cohort studies are necessary to validate these findings.

Association of sensitivity to thyroid hormones with all-cause mortality in euthyroid US adults: A nationwide cohort study.

Background This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results Individuals in quartile 4th (Q4) had lower all-cause mortality than those in quartile 1st (Q1) of FT3/FT4 ratio (OR 0.70, 95% CI (0.51, 0.94)). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (OR 1.43, 95% CI (1.05, 1.96)) (P <0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Associations of Serum Iron Status with MAFLD and Liver Fibrosis in the USA: a Nationwide Cross-Section Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology characterized by liver steatosis. Iron status is related to many metabolic diseases. However, the researches on the associations of serum iron status with MAFLD are limited. The objective of this study was to investigate the associations of serum iron status biomarkers with MAFLD and liver fibrosis. A total of 5892 adults were enrolled in the current cross-sectional study using the 2017-March 2020 National Health and Nutrition Examination Survey. Liver steatosis and liver fibrosis were defined by the median values of controlled attenuation parameter ≥ 274 dB/m and liver stiffness measurement ≥ 8 kPa, respectively. The multivariable logistic/linear regression and restricted cubic spline analysis were conducted. After adjusting for potential confounders, higher ferritin levels were associated with higher odds of MAFLD (OR 4.655; 95% CI 2.301, 9.418) and liver fibrosis (OR 7.013; 95% CI 3.910, 12.577). Lower iron levels were associated with a higher prevalence of MAFLD (OR 0.622; 95% CI 0.458, 0.844) and liver fibrosis (OR 0.722; 95% CI 0.536, 0.974). Lower transferrin saturation (TSAT) was associated with a higher prevalence of MAFLD (OR 0.981; 95% CI 0.970, 0.991) and liver fibrosis (OR 0.988; 95% CI 0.979, 0.998). Higher ferritin levels, lower iron levels, and TSAT were associated with a higher prevalence of MAFLD and liver fibrosis. This study extended the knowledge of modifying iron status to prevent MAFLD and liver fibrosis. More prospective and mechanism studies were warranted to confirm the conclusions.

Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross­sectional Study.

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations.

Associations between blood essential metal mixture and serum uric acid: a cross-sectional study.

Introduction: Although several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear. Methods: We performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA. Results: In the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [ß=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed. Discussion: In conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.

Central Sensitivity to Free Triiodothyronine With MAFLD and Its Progression to Liver Fibrosis in Euthyroid Adults.

CONTEXT: Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis remained unclear. OBJECTIVE: We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults. METHODS: This community-based study included 7906 euthyroid adults. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, Thyroid Feedback Quantile-based Index by FT4 (TFQIFT4), and Thyroid Feedback Quantile-based Index by FT3 (TFQIFT3), indicating peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). Multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted. RESULTS: Compared with participants in the first quartile (Q1), the prevalence of MAFLD was increased by 62% in the fourth quartile (Q4) of FT3/FT4 ratio (OR 1.62; 95% CI [1.38, 1.91]) and by 40% in Q4 of TFQIFT3 (OR 1.40; 95% CI [1.18, 1.65]) (both P < .05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis was increased by 45% in Q4 of TFQIFT3 (OR 1.45; 95% CI [1.03, 2.06]) (P < .05) in participants with MAFLD. CONCLUSION: Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies are warranted to confirm these conclusions.

Efficacy and safety of pregabalin in eye pain: A systematic review.

BACKGROUND: The pregabalin is approved for the management of persistent pain. The aim of this study is to assess the advantages and disadvantages of the use of pregabalin in eye pain management. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched until January 2022 for randomized controlled trials. Randomized, double-blinded trials comparing pregabalin with placebo in eye pain management were included. The primary outcome was visual analog scale or numerical rating scale at acute (24 hours) and chronic (≥7 days after surgery) timepoints. The secondary outcomes were analgesic medication requirements and pregabalin-related complications (nausea, vomiting, dizziness, and headache). We also compared the effect of pregabalin on dry-eye syndrome. MAIN RESULTS: Six relevant articles were identified that studied the use of pregabalin as pain relief for photorefractive keratectomy (n = 2), laser epithelial keratomileusis (n = 1), laser-assisted in situ keratomileusis (n = 1), eyelid surgery (n = 1), and dacryocystorhinostomy (n = 1). Pregabalin was associated with a significant reduction in pain scores (95% confidence interval = -0.41 [-0.76--0.06]) 24 hours after surgical procedures. The data were insufficient to draw conclusions regarding dry eye symptoms. Because of the high heterogeneity of outcomes regarding adverse effects, there is no conclusion regarding the safety of pregabalin in eye pain. CONCLUSIONS: Pregabalin reduced acute eye pain but had no significant effect on long-term analgesia after ophthalmological surgery in adults. It had no effect on dry-eye symptoms after ocular surgery. Further studies on the safety of pregabalin in eye pain management are required to draw solid conclusions.

Associations of metal profiles in blood with thyroiditis: a cross-sectional study.

Autoimmune thyroiditis (AIT) is increasingly common, and serological markers include thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). To determine if selected metals influence thyroiditis antibody positivity, this cross-sectional study investigated associations between metals and thyroiditis antibody status. Healthy individuals (n = 1104) completed a questionnaire and underwent checkups of anthropometric parameters, thyroid function status, and levels of seven metals in blood (magnesium, iron, calcium, copper, zinc, manganese, and lead). Associated profiles of glyco- and lipid metabolism were also established. Logistic regression and restricted cubic spline (RCS) regression analysis were applied to adjudge associations between metals and TPOAb and TgAb status. It was found that, after adjusting for likely cofounding factors, participants with antibody positivity had significantly lower serum concentrations of magnesium and iron. When serum magnesium levels were analyzed in quartiles, the odds ratios of quartile 4 were 0.329-fold (95% confidence interval (CI): 0.167-0647) and 0.259-fold (95% CI 0.177-0.574) that of quartile 1 regarding TPOAb and TgAb positivity (P = 0.004, 0.003). After adjustment, the RCS analysis detected nonlinear associations between iron and TPOAb and TgAb positivity (P < 0.01, both). In stratified analyses, these associations regarding magnesium and iron remained for women of reproductive age, but not for postmenopausal women and men. We conclude that lower serum levels of magnesium and iron are associated with incremental positivity of thyroiditis antibodies and may be among the most important metals contributing to AIT in women of reproductive age.

Associations of phthalates with NAFLD and liver fibrosis: A nationally representative cross-sectional study from NHANES 2017 to 2018.

Objective: Although phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis. Methods: Data of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis. Results: After adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: ß, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis. Conclusions: All in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

Associations of serum folate and vitamin C levels with metabolic dysfunction-associated fatty liver disease in US adults: A nationwide cross-sectional study.

Background: Clinical research results on the relationship between folate and non-alcoholic fatty liver disease are contradictory. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed concept. Evidence about the relationship between serum folate and MAFLD, especially considering the status of serum vitamin C, is scarce. This study was aimed to investigate the association of serum folate levels with the prevalence of MAFLD, and further to analyze the potential impact of serum vitamin C status on their association. Methods: Totally 2,797 participants from National Health and Nutrition Examination Survey (NHANES) 2017-2018 were included. Vibration-controlled transient elastography was used to detect liver steatosis and fibrosis. Participants were divided in groups based on the tertiles of serum folate or vitamin C, and the serum folate or vitamin C level in T1 was low. Logistic regression analysis in the complex sample module was performed to illustrate the association of serum folate levels with the prevalence of MAFLD. Stratification analysis by serum vitamin C status was performed as well. Results: Compared with the serum folate levels of T1 group, participants in the T3 group had 47.9% lower risk of MAFLD [OR = 0.521 (95% CI: 0.401-0.677)]. However, when participants were stratified by serum vitamin C levels, there was no association between the serum folate levels and MAFLD in the T1 or T2 group. Among participants in the T3 group of vitamin C status, participants in the T3 group of serum folate had a 63.6% lower risk of MAFLD compared with the T1 group [OR = 0.364 (95% CI: 0.147-0.903)]. Conclusions: High serum folate level is associated with lower prevalence of MAFLD, especially in participants with sufficient vitamin C.

GSK3ß inhibitor TDZD8 ameliorates brain damage through both ROS scavenging and inhibition of apoptosis in hyperglycaemic subarachnoid haemorrhage rats.

Hyperglycaemia is known to be associated with unfavourable outcomes in subarachnoid haemorrhage (SAH), but the pathogenic mechanism is unclear, and there is also a lack of effective therapeutic drugs in clinical practice. Phosphorylation of GSK3ß at serine 9 can inhibit its activity to further worsen SAH. The aim of the present study was to evaluate the protective effect and the potential mechanism of the GSK3ß inhibitor TDZD8 on brain injury in a hyperglycaemic SAH rat model. Hyperglycaemia was induced by intraperitoneal injection of streptozocin for 3 days. The SAH model was established by injecting fresh autologous femoral artery blood into the prechiasmatic cistern. p-GSK3ß (Ser9) expression was induced by intraperitoneal injection of TDZD8 (30 min post-SAH). The expression levels of GSK3ß, p-GSK3ß, SOD1/2, caspase 3, Bax and Bcl-2 were detected by western blot analysis. Terminal deoxynucleotidyl transferase dUTP nick end-labelling (TUNEL) staining was used to detect neuronal apoptosis of basal temporal lobe. Neurological scores were calculated to determine behavioural recovery. Neuronal survival was detected by Nissl staining. Hyperglycaemia significantly decreased p-GSK3ß expression, further exacerbated neurobehavioural deficits and increased oxidative stress and neuronal apoptosis in the brain after SAH compared to normal glycaemic SAH rats and hyperglycaemic rats. In addition, hyperglycaemic SAH rats had obvious oxidative stress and apoptosis. However, TDZD8 effectively decreased cleaved caspase 3 expression and TUNEL-positive cells and increased the Bcl2/Bax ratio, expression of SOD1/2 and activity of superoxide dismutase (SOD) enzyme compared with hyperglycaemic SAH rats. The GSK3ß inhibitor TDZD8 has therapeutic potential for hyperglycaemic SAH. The neuroprotective effect of TDZD8 appears to be mediated through its antioxidative and antiapoptotic activity.

Associations of Uric Acid With Liver Steatosis and Fibrosis Applying Vibration Controlled Transient Elastography in the United States: A Nationwide Cross-Section Study.

Background and objective: Serum uric acid (UA) is related to many metabolic diseases. However, the association of UA with liver diseases was not very clear. The objective of this study is to clarify the relationship of UA with liver steatosis and fibrosis. Methods: This is a cross-sectional study of 4364 people of National Health and Nutrition Examination Survey (NHANES) 2017-2018. Liver steatosis and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) using Vibration-controlled transient elastography (VCTE). Linear and logistic regressions were performed. Results: After adjusting for potential confounders, UA levels were associated with the prevalence of liver steatosis [OR=2.097 (95%CI: 1.245, 3.534)] and liver fibrosis [OR=2.983 (95%CI: 1.797, 4.952)]. Furthermore, the results were consistent in the subgroup analyses of males and females. Conclusions: UA levels were positively associated with the prevalence of liver steatosis and fibrosis.

Visually-guided Grip Selection for Soft-Hand Exoskeleton.

This paper presents a visually-guided grip selection based on the combination of object recognition and tactile feedback of a soft-hand exoskeleton intended for hand rehabilitation. A pre-trained neural network is used to recognize the object in front of the hand exoskeleton, which is then mapped to a suitable grip type. With the object cue, it actively assists users in performing different grip movements without calibration. In a pilot experiment, one healthy user completed four different grasp-and-move tasks repeatedly. All trials were completed within 25 seconds and only one out of 20 trials failed. This shows that automated movement training can be achieved by visual guidance even without biomedical sensors. In particular, in the private setting at home without clinical supervision, it is a powerful tool for repetitive training of daily-living activities.

Related Psychosocial Factors and Delivery Mode of Depression and Anxiety in Primipara in Late Pregnancy.

Studies in recent years show that the delivery process, the choice of delivery mode, and the delivery outcome of primiparas are affected by their mental state. With the transformation of the medical model from the single biomedical model to the biopsychosocial medical model, the influence of social psychological factors on maternal psychological state has aroused heated discussion among clinical scholars. In this study, 480 cases of normal primiparas who had regular prenatal examination and delivered in hospital were selected as the research object. The Hospital Anxiety and Depression Scale (HAD) was used to record the depressive anxiety state of all study subjects in the third trimester, and we analyzed the effects of age, education background of pregnant women and their spouses, the nature of jobs, family income, prenatal and pregnancy health status, medical insurance status, attend pregnant women's school, and accompanying status of family member on their depressive anxiety state. The influence of depression and anxiety on delivery mode was analyzed. The result showed that the age, health status during prenatal and pregnancy, accompanying status of family members, and attend pregnant women's school are the independent risk factors affecting depression and anxiety status of primiparas during late pregnancy. Antenatal depression and anxiety have certain influence on the choice of the delivery mode of pregnant women. Targeted psychological intervention for primiparas with high-risk factors is helpful to improve their psychological state and reduce the rate of cesarean section.

SPTBN1 Prevents Primary Osteoporosis by Modulating Osteoblasts Proliferation and Differentiation and Blood Vessels Formation in Bone.

Osteoporosis is a common systemic skeletal disorder that leads to increased bone fragility and increased risk of fracture. Although ßII-Spectrin (SPTBN1) has been reported to be involved in the development of various human cancers, the function and underlying molecular mechanisms of SPTBN1 in primary osteoporosis remain unclear. In this study, we first established a primary osteoporosis mouse model of senile osteoporosis and postmenopausal osteoporosis. The results showed that the expression of SPTBN1 was significantly downregulated in primary osteoporosis mice model compared with the control group. Furthermore, silencing of SPTBN1 led to a decrease in bone density, a small number of trabecular bones, wider gap, decreased blood volume fraction and number of blood vessels, as well as downregulation of runt-related transcription factor 2 (Runx2), Osterix (Osx), Osteocalcin (Ocn), and vascular endothelial growth factor (VEGF) in primary osteoporosis mice model compared with the control group. Besides, the silencing of SPTBN1 inhibited the growth and induced apoptosis of mouse pre-osteoblast MC3T3-E1 cells compared with the negative control group. Moreover, the silencing of SPTBN1 significantly increased the expression of TGF-ß, Cxcl9, and the phosphorylation level STAT1 and Smad3 in MC3T3-E1 cells compared with the control group. As expected, overexpression of SPTBN1 reversed the effect of SPTBN1 silencing in the progression of primary osteoporosis both in vitro and in vivo. Taken together, these results suggested that SPTBN1 suppressed primary osteoporosis by facilitating the proliferation, differentiation, and inhibition of apoptosis in osteoblasts via the TGF-ß/Smad3 and STAT1/Cxcl9 pathways. Besides, overexpression of SPTBN1 promoted the formation of blood vessels in bone by regulating the expression of VEGF. This study, therefore, provided SPTBN1 as a novel therapeutic target for osteoporosis.

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGF-ß and EGFR signaling pathways in obstructive nephropathy.

We have recently shown that histone deacetylase 6 (HDAC6) is critically involved in the pathogenesis of acute kidney injury. Its role in renal fibrosis, however, remains unclear. In this study, we examined the effect of ricolinostat (ACY-1215), a selective inhibitor of HDAC6, on the development of renal fibrosis in a murine model induced by unilateral ureteral obstruction (UUO). HDAC6 was highly expressed in the kidney following UUO injury, which was coincident with deposition of collagen fibrils and expression of α-smooth muscle actin, fibronectin, and collagen type III. Administration of ACY-1215 reduced these fibrotic changes and inhibited UUO-induced expression of transforming growth factor-ß1 and phosphorylation of Smad3 while increasing expression of Smad7. ACY-1215 treatment also suppressed phosphorylation of epidermal growth factor receptor (EGFR) and several signaling molecules associated with renal fibrogenesis, including AKT, STAT3, and NF-κB in the injured kidney. Furthermore, ACY-1215 was effective in inhibiting dedifferentiation of renal fibroblasts to myofibroblasts and the fibrotic change of renal tubular epithelial cells in culture. Collectively, these results indicate that HDAC6 inhibition can attenuate development of renal fibrosis by suppression of transforming growth factor-ß1 and EGFR signaling and suggest that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis.