BackgroundDiabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN.MethodsRats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected.ResultsCQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs.ConclusionsCQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.

ObjectiveIn China, rural residents experience poorer health conditions and a higher disease burden compared to urban residents but have lower healthcare services utilization. Rather than an insurance focus on enhanced healthcare services utilization, we aim to examine that whether an income shock, in the form of China’s New Rural Pension Scheme (NRPS), will affect outpatient, inpatient and discretionary over-the-counter drug utilization by over 60-year-old rural NRPS residents.MethodsProviding a monthly pension of around RMB88 (USD12.97), NRPS covered all rural residents over 60 years old. Fuzzy regression discontinuity design (FRDD) was employed to explore the NRPS causal effect on healthcare services utilization, measured by outpatient and inpatient visits and discretionary over-the-counter drug purchases. The nationwide China Health and Retirement Longitudinal Study (CHARLS) 2018 provided the data.ResultsWithout significant changes in health status and medication needs, 60-plus-year-old NRPS recipients significantly increased the probability of discretionary OTC drug purchases by 33 percentage points. NRPS had no significant effect on the utilization of outpatient and inpatient utilization. The increase in the probability of discretionary OTC drug purchases from the NRPS income shock was concentrated in healthier and low-income rural residents. Robustness tests confirmed that FRDD was a robust estimation method and our results are robust.ConclusionNRPS was an exogenous income shock that significantly increased the probability of discretionary over-the-counter drug purchases among over 60-year-old rural residents, but not the utilization of inpatient or outpatient healthcare services. Income remains an important constraint for rural residents to improve their health. We recommend policymakers consider including commonly used over-the-counter drugs in basic health insurance reimbursements for rural residents; provide health advice for rural residents to make discretionary over-the-counter drug purchases; and to mount an information campaign on over-the-counter drug purchasing in order to increase the health awareness of rural residents.

BackgroundMajor depressive disorder (MDD) is a highly heterogeneous mental illness and a major public health problem worldwide. A large number of observational studies have demonstrated a clear association between MDD and coronary heart disease (CHD), and some studies have even suggested that the relationship is bidirectional. However, it was unknown whether any causal relationship existed between them and whether causality was bidirectional in such an instance. Thus, we aimed to determine whether there is a bidirectional causal relationship between major depressive disorders and coronary heart disease.MethodsOur two-sample Bidirectional Mendelian Randomization Study consisted of two parts: forward MR analysis regarded MDD as exposure and CHD as the outcome, and reverse MR analysis considered CHD as exposure and MDD as the outcome. Summary data on MDD and CHD were obtained from the IEU Open GWAS database. After screening criteria(P < 5×10-8\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$5\times {10}^{-8}$$\end{document}), 47 MDD-associated SNPs and 39 CHD-associated SNPs were identified. The inverse-variance weighted (IVW) method, ME-Egger regression, and weighted median method were used to estimate causality. In addition, sensitivity methods, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out method, were applied to ensure the robustness of causal estimation.ResultsBased on the MR-Egger regression intercept test results, there did not appear to be any horizontal pleiotropy in this study (MDD: intercept = -0.0000376, P = 0.9996; CHD: intercept = -0.0002698, P = 0.920). Accordingly, IVW results suggested consistent estimates of causal effect values. The results showed that people with MDD increased the risk of CHD by 14.7% compared with those without MDD (OR = 1.147, 95%CI: 1.045–1.249, P = 0.009). But there was no direct evidence that CHD would increase the risk of MDD(OR = 1.008, 95%CI: 0.985–1.031, P = 0.490). The heterogeneity test and funnel plot showed no heterogeneity in 47 SNPs of MDD (Q = 42.28, I2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$${I}^{2}$$\end{document}=0, P = 0.629), but there was heterogeneity in 39 SNPs of CHD (Q = 62.48, I2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$${I}^{2}$$\end{document}=39.18%, P = 0.007). The leave-one-out method failed to identify instances where a single SNP was either biased toward or dependent on the causation.ConclusionOur study supports a one-way causal relationship between MDD and CHD, but there is no bidirectional causal relationship. MDD increases the risk of CHD, but there is no evidence that CHD increases the risk of MDD. Therefore, the influence of psychological factors should also be considered in the prevention and treatment of CHD. For MDD patients, it is necessary to prevent cardiovascular diseases.

IntroductionAlthough the relationships between parental mental health and child internalizing and externalizing problems have been explored by previous studies, the pathways between these two variables need further exploration. The present study aims to explore the relationships between parental depression and child internalizing and externalizing problems and to examine the roles of parenting stress and child maltreatment in those relationships within the Chinese cultural context.MethodData were collected from 855 Chinese families with preschool-aged children, and mediation analysis was used to examine the pathways between these variables.ResultsThe results show that parental depression is positively associated with child internalizing and externalizing problems, and child maltreatment and the combination of parenting stress and child maltreatment mediated the relationships between parental depression and child internalizing and externalizing problems, respectively. These findings suggest that parental depression not only has a direct effect on child internalizing and externalizing problems but also has an indirect effect via parenting stress and child maltreatment.DiscussionDecreasing the levels of parenting stress and child maltreatment should be applied in interventions to break the relationships between parental depression and child internalizing and externalizing problems within the Chinese cultural context.

Introduction: Bone morphogenetic proteins (BMPs) play a crucial role in bone formation and differentiation. Recent RNA-Seq results suggest that BMPs may be involved in the sex differentiation of P. sinensis, yet more relevant studies about BMPs in P. sinensis are lacking.Methods: Herein, we identified BMP gene family members, analyzed the phylogeny, collinear relationship, scaffold localization, gene structures, protein structures, transcription factors and dimorphic expression by using bioinformatic methods based on genomic and transcriptomic data of P. sinensis. Meanwhile, qRT-PCR was used to verify the RNA-Seq results and initially explore the function of the BMPs in the sex differentiation of P. sinensis.Results: A total of 11 BMP genes were identified, 10 of which were localized to their respective genomic scaffolds. Phylogenetic analysis revealed that BMP genes were divided into eight subfamilies and shared similar motifs (“WII”, “FPL”, “TNHA”, “CCVP”, and “CGC”) and domain (TGF-β superfamily). The results of the sexually dimorphic expression profile and qRT-PCR showed that Bmp2, Bmp3, Bmp15l, Bmp5, Bmp6 and Bmp8a were significantly upregulated in ovaries, while Bmp2lb, Bmp7, Bmp2bl and Bmp10 were remarkable upregulated in testes, suggesting that these genes may play a role in sex differentiation of P. sinensis.Discussion: Collectively, our comprehensive results enrich the basic date for studying the evolution and functions of BMP genes in P. sinensis.

Neurological diseases such as traumatic brain injury, cerebral ischemia, Parkinson’s, and Alzheimer’s disease usually occur in the central and peripheral nervous system and result in nervous dysfunction, such as cognitive impairment and motor dysfunction. Long-term clinical intervention is necessary for neurological diseases where neural stem cell transplantation has made substantial progress. However, many risks remain for cell therapy, such as puncture bleeding, postoperative infection, low transplantation success rate, and tumor formation. Sustained drug delivery, which aims to maintain the desired steady-state drug concentrations in plasma or local injection sites, is considered as a feasible option to help overcome side effects and improve the therapeutic efficiency of drugs on neurological diseases. Natural polymers such as silk fibroin have excellent biocompatibility, which can be prepared for various end-use material formats, such as microsphere, gel, coating/film, scaffold/conduit, microneedle, and enables the dynamic release of loaded drugs to achieve a desired therapeutic response. Sustained-release drug delivery systems are based on the mechanism of diffusion and degradation by altering the structures of silk fibroin and drugs, factors, and cells, which can induce nerve recovery and restore the function of the nervous system in a slow and persistent manner. Based on these desirable properties of silk fibroin as a carrier with sustained-release capacity, this paper discusses the role of various forms of silk fibroin-based drug delivery materials in treating neurological diseases in recent years.