AZIN2 is associated with apoptosis of germ cells in undescended testis.

Undescended testis (UDT), known as cryptorchidism (CRY), is a common congenital disorder in which one or both testicles do not descend normally into the scrotum. A unilateral UDT model was established by inducing UDT in mice through surgery. The results showed that the testis in the UDT model group was abnormal; the lumen of the seminiferous tubule was atrophic; apoptosis, necrosis and shedding were observed in many of the germ cells; the level of sex hormones was abnormal; and mature sperm was reduced. Subsequently, transcriptome sequencing was conducted on the testicular tissue of UDT model mice. Through analysis and verification of differential genes, AZIN2 was identified as playing a key role in the decline in male fertility caused by cryptorchidism. AZIN2 expression and spermine content was down-regulated in the testis of the UDT group. We then used a combination of hypoxanthine and xanthine to create a GC-1 cell damage model. In this model, AZIN2 expression and spermine content was down-regulated. When si-Azin2 transfected GC-1 cells, cell viability and proliferation were decreased. However, in the GC-1 cell damage model transfected with Azin2 over-expressed plasmid, AZIN2 expression and spermine content was up-regulated, reversing the cell damage caused by hypoxanthine and xanthine, and restoring the proliferation ability of GC-1 cells. These results indicate that in UDT, down-regulated AZIN2 expression is a factor in testicular damage. This discussion of the connection between AZIN2 and germ cells has important clinical significance as it provides an important reference for the diagnosis and treatment of cryptorchidism.

Maturity Classification of Rapeseed Using Hyperspectral Image Combined with Machine Learning.

Oilseed rape is an important oilseed crop planted worldwide. Maturity classification plays a crucial role in enhancing yield and expediting breeding research. Conventional methods of maturity classification are laborious and destructive in nature. In this study, a nondestructive classification model was established on the basis of hyperspectral imaging combined with machine learning algorithms. Initially, hyperspectral images were captured for 3 distinct ripeness stages of rapeseed, and raw spectral data were extracted from the hyperspectral images. The raw spectral data underwent preprocessing using 5 pretreatment methods, namely, Savitzky-Golay, first derivative, second derivative (D2nd), standard normal variate, and detrend, as well as various combinations of these methods. Subsequently, the feature wavelengths were extracted from the processed spectra using competitive adaptive reweighted sampling, successive projection algorithm (SPA), iterative spatial shrinkage of interval variables (IVISSA), and their combination algorithms, respectively. The classification models were constructed using the following algorithms: extreme learning machine, k-nearest neighbor, random forest, partial least-squares discriminant analysis, and support vector machine (SVM) algorithms, applied separately to the full wavelength and the feature wavelengths. A comparative analysis was conducted to evaluate the performance of diverse preprocessing methods, feature wavelength selection algorithms, and classification models, and the results showed that the model based on preprocessing-feature wavelength selection-machine learning could effectively predict the maturity of rapeseed. The D2nd-IVISSA-SPA-SVM model exhibited the highest modeling performance, attaining an accuracy rate of 97.86%. The findings suggest that rapeseed maturity can be rapidly and nondestructively ascertained through hyperspectral imaging.

Spatiotemporal associations between hand, foot and mouth disease and meteorological factors over multiple climate zones.

Prior studies of hand, foot, and mouth disease (HFMD) have often observed inconsistent results regarding meteorological factors. We propose the hypothesis that these meteorological associations vary in regions because of the heterogeneity of their geographical characteristics. We have tested this hypothesis by applying a geographical detector and Bayesian space-time hierarchy model to measure stratified spatiotemporal heterogeneity and local associations between meteorological factors and HFMD risk in five climate zones in China from January 2016 to December 2017. We found a significant spatial stratified heterogeneity in HFMD risk and climate zone explained 15% of the spatial stratified heterogeneity. Meanwhile, there was a significant temporal stratified heterogeneity of 14% as determined by meteorological factors. Average temperatures and relative humidity had a significant positive effect on HFMD in all climate zones, they were the most obvious in the southern temperate zone. In northern temperate, southern temperate, northern subtropics, middle subtropics and southern subtropics climate zone, a 1 °C rise in temperature was related to an increase of 3.99%, 13.76%, 4.38%, 3.99%, and 7.74% in HFMD, and a 1% increment in relative humidity was associated with a 1.51%, 5.40%, 2.21%, 3.44%, and 4.78% increase, respectively. These findings provide strong support for our hypotheses that HFMD incidence has a significant spatiotemporal stratified heterogeneity and different climate zones have distinct influences on the disease. These findings provide strong support for our hypotheses: HFMD incidence had significant spatiotemporal stratified heterogeneity and different climate zones had distinct influences on it. The study suggested that HFMD prevention and policy should be made according to meteorological variation in each climate zone.

Spatial Pattern Evolution and Influencing Factors on Agricultural Non-Point Source Pollution in Small Town Areas under the Background of Rapid Industrialization.

To promote sustainable agricultural development in small town areas during rapid industrialization, it is important to study the evolution of agricultural non-point source pollution (ANSP) and its influencing factors in small town areas in the context of rapid industrialization. The non-point source inventory method was used to study the characteristics of ANSP evolution in 14 small town areas in Gongyi City from 2002 to 2019. Using the spatial Durbin model and geographical detectors, the factors influencing ANSP in small town areas were analyzed in terms of spatial spillover effects and the spatial stratified heterogeneity. The results showed a zigzagging downward trend of ANSP equivalent emissions over time. Spatially, the equivalent emissions of ANSP showed a distribution pattern of being high in the west and low in the east. There was a significant positive global spatial autocorrelation feature and there was an inverted "U-shaped" Environmental Kuznets Curve relationship between industrialization and ANSP. Affluence, population size, and cropping structure positively contributed to the reduction of ANSP. Population size, land size, and industrialization were highly influential factors affecting the spatial variation of ANSP and the interaction of these factors was bivariate or nonlinearly enhanced. This study provides a feasible reference for policymakers and managers to develop reasonable management measures to mitigate ANSP in small town areas during rapid industrialization.

Activation of the Chemokine Receptor CCR1 and Preferential Recruitment of Gαi Suppress RSV Replication: Implications for Developing Novel Respiratory Syncytial Virus Treatment Strategies.

Respiratory syncytial virus (RSV) is a major pathogen that can cause acute respiratory infectious diseases of the upper and lower respiratory tract, especially in children, elderly individuals, and immunocompromised people. Generally, following viral infection, respiratory epithelial cells secrete cytokines and chemokines to recruit immune cells and initiate innate and/or adaptive immune responses. However, whether chemokines affect viral replication in nonimmune cells is rarely clear. In this study, we detected that chemokine CCL5 was highly expressed, while expression of its receptor, CCR1, was downregulated in respiratory epithelial cells after RSV infection. When we overexpressed CCR1 on respiratory epithelial cells in vivo or in vitro, viral load was significantly suppressed, which can be restored by the neutralizing antibody for CCR1. Interestingly, the antiviral effect of CCR1 was not related to type I interferon (IFN-I), apoptosis induction, or viral adhesion or entry inhibition. In contrast, it was related to the preferential recruitment and activation of the adaptor Gαi, which promoted inositol 1,4,5-triphosphate receptor type 3 (ITPR3) expression, leading to inhibited STAT3 phosphorylation; explicitly, phosphorylated STAT3 (p-STAT3) was verified to be among the important factors regulating the activity of HSP90, which has been previously reported to be a chaperone of RSV RNA polymerase. In summary, we are the first to reveal that CCR1 on the surface of nonimmune cells regulates RSV replication through a previously unknown mechanism that does not involve IFN-I induction. IMPORTANCE Our results revealed a novel mechanism by which RSV escapes innate immunity. That is, although it induces high CCL5 expression, RSV might attenuate the binding of CCL5 by downregulating the expression of CCR1 in respiratory epithelial cells to weaken the inhibitory effect of CCR1 on HSP90 activity and thereby facilitate RSV replication in nonimmune cells. This study provides a new target for the development of co-antiviral inhibitors against other components of the host and co-molecular chaperone/HSP90 and provides a scientific basis for the search for effective broad-spectrum antiviral drugs.

Evaluation of the Effectiveness of Rural Revitalization and an Improvement Path: A Typical Old Revolutionary Cultural Area as an Example.

At present, the focus of global attention is on implementing rural revitalization strategies. However, constructing a set of scientifically based evaluation indexes for the evaluation of the effectiveness of rural revitalization implementation, exploring the implementation plan for rural revitalization, has become a common concern and a focus of discussion in political and academic circles. This study used a typical rural revitalization demonstration area in China as an example. We proposed a theoretical framework for rural revitalization research and constructed an index evaluation system for the evaluation of the effectiveness of rural revitalization implementation and influencing factors from two perspectives: material life and spiritual life. The results were as follows: Differences were found in the implementation effectiveness of rural revitalization strategies in the study area; especially, in areas with obvious rural cultural characteristics, their implementation level was relatively high. The implementation effectiveness of rural revitalization strategies was the result of multi-factor interactions. The village greening rate, innovation ability, and the age of village supporters were the main factors affecting rural revitalization, and the interaction effects of a village's innovation ability and other factors were significant. Therefore, we argue that in the process of promoting the sustainable development of villages, it is necessary to prominent the characteristics of village construction and improve the effectiveness of the implementation of village revitalization strategies at both the material and spiritual levels.

The challenge of healthcare big data to China's commercial health insurance industry: evaluation and recommendations.

BACKGROUND: China's social medical insurance system faces challenges in financing, product coverage, patient health responsibility sharing and data security, which commercial health insurance companies can help address. Confronting accelerated population aging, the rapid increase of patients with chronic diseases and the maternal and child healthcare needs created by the three-child policy, the Chinese government has encouraged the development of commercial health insurance. But China's commercial health insurance companies face financial sustainability problems, limited product ranges and high operating costs. At the same time, the informatization level of China's healthcare industry, and the value of healthcare big data, is increasing. We analyze and describe the potential application of healthcare big data in the life cycle of China's commercial health insurance system and provide specific action plans for Chinese commercial health insurance companies; identify the challenges to commercial health insurers; and make recommendations for the application of big health data by commercial health insurers. Our recommendations inform healthcare policy makers on the development of commercial health insurance and the improvement of the healthcare financing system. We not only verify the value of healthcare big data, but also identify specific ways that healthcare big data plays in the development of commercial health insurance. Based on the research results, we recommend new policies for government and new uses of healthcare big data for commercial health insurance institutions. The benign development of commercial health insurance will improve the level of health services in China. METHODS: By interviewing health insurance managers (including actuaries, product managers, business executives, information technology medical workers, and commercial health insurance personnel) and by accessing research papers, industry reports, news reports and public information disclosure documents about commercial health insurance, we describe the impact of healthcare big data on the life cycle of commercial health insurance products and processes. RESULTS: We identify the issues and challenges of commercial health insurers in the use of healthcare big data, and advance specific strategies to expand the use of healthcare big data. In the life cycle of commercial health insurance products, healthcare big data can improve premium income, control medical costs and increase operational efficiency. First, healthcare big data can increase premiums, products and services by attenuating moral hazard and adverse selection problems, where high quality clients over-pay and high-risk clients underpay for health insurance. Second, healthcare big data can reduce medical expenses compensation pay-outs by promoting the establishment of a management medical system. Finally, the use of healthcare big data improves operational efficiency by increasing payment speeds, identifying fraud and increasing claim verification processes through automating payments and reducing offline processes. We discuss the obstacles to obtain healthcare big data confronting commercial health insurance companies. The sharing and data mining of healthcare big data brings privacy risks to the insured and there are significant differences in data standards and quality of healthcare big data that limit the application of healthcare big data in commercial health insurance. We recommend that national, regional and local government departments coordinate policies to facilitate the cooperation between commercial health insurance companies and regional healthcare big data platforms. In terms of technology, we recommend the establishment of data sharing platforms and data exchange mechanism across institutions and regions according to nation-wide standards and specifications. Government management departments should establish healthcare big data standards and specification system, promote the construction of healthcare big data and ensure the integrity, authenticity and reliability of health data. We recommend data quality continuous improvement and management mechanisms that combine technology and management. Government regulation should oversee commercial health insurance institutions and establish data security management systems to monitor and supervise the privacy of personal data. CONCLUSIONS: Healthcare big data can play an important role in the development of China's commercial health insurance industry. Healthcare big data can increase commercial health insurers' financial viability while providing improved, and cost-effective, products and services. By providing more and better information to insurers, healthcare big data attenuates the asymmetric information problem, addressing moral hazard and adverse selection problems. By combining hospital and medical organization management information systems with insurers' data management, healthcare big data can help insurers set sustainable premiums, control medical costs and promote operational efficiency. At present, the informatization degree of China's healthcare industry remains limited. To improve the performances, products and services of commercial health insurers, we recommend government reforms in healthcare big data, such as expanding medical industry cooperation; further developing the processes of applying healthcare big data; augmenting data sharing; addressing privacy risks; setting data standards; and improving data quality.

An Improved Gray Neural Network Method to Optimize Spatial and Temporal Characteristics Analysis of Land-Use Change.

In this article, the principles of the gray model and BP neural network model are analyzed, and the characteristics of land-use change and spatial and temporal distribution are studied in-depth, and at the same time, to explore the influence of land-use change on ESV, the relationship between the two is analyzed using gray correlation degree, and a mathematical model is constructed to maximize the benefits of the regional system, coupling economic and ecological benefits, combined with Geo SOS-FLUS model to achieve the optimization of land use. This article constructs a combined prediction model of a gray neural network. The gray differential equation parameters correspond to the weights and thresholds of the neural network, and the optimized parameters are determined by training the neural network to make it stable. Then the training results of the BP neural network are fitted with the results obtained from the gray GM (1.1) model. Finally, the prediction results of the three models, gray GM (1.1), BP God Meridian, and gray neural network model, are compared and analyzed. The global spatial autocorrelation and local spatial aggregation patterns of regional soil erosion and its erosion factors are analyzed using the Exploratory Spatial Data Analysis (ESDA) method in spatial measurement theory.

Analysis of Human Geography Space Based on Geographic Information System in the Context of Rural Revitalization.

Nowadays, it is proposed "Firmly implement the rural revitalization strategy", and rural revitalization has risen to the level of national-level strategy. Human geography is to respond to the cultural effects produced by various residents with similar living habits together. As a spatial science, GIS, with its unique spatial viewpoint and spatial thinking, reveals the spatial distribution characteristics and dynamic change laws of various things and phenomena from spatial interconnections and interactions. From the spatial objects studied by GIS, this paper puts forward thoughts on the new directions of GIS development: expanding from Earth space to cosmic space, it is necessary to build coordinate system and cosmic geospatial information system, lunar geospatial information system, etc.; extending from outdoor space to indoor space, it is necessary to develop indoor geospatial information system and expand to underwater space and underground space; from macro to micro space, we can develop sports geospatial information system for games, human geospatial information system for life and health management, etc.; facing the era of big data, we can develop theories and methods of spatial analysis of big data and contribute to the development of big data science. Thus, the way of constructing GIS based on human geospatial analysis can be built in the context of the era of rural revitalization. The purpose of the research in this paper is mainly to show the role of GIS in the construction of human geography space. Through GIS means, it can better gather some villages in human geography, have a better form of expression, and can better construct a spatial information system.

Spatio-temporal variation in tuberculosis incidence and risk factors for the disease in a region of unbalanced socio-economic development.

BACKGROUND: Previous research pointed to a close relationship between the incidence of tuberculosis (TB) in aging populations and socio-economic conditions, however there has been lack of studies focused on a region of unbalanced socio-economic development. The aim of this paper is to explore the spatio-temporal variation in TB incidence and examine risk determinants of the disease among aging populations in a typical region. METHODS: Data on TB-registered cases between 2009 and 2014, in addition to social-economic factors, were collected for each district/county in Beijing, Tianjin and Hebei, a region characterized by an aging population and disparities in social-economic development. A Bayesian space-time hierarchy model (BSTHM) was used to reveal spatio-temporal variation in the incidence of TB among the elderly in this region between 2009 to 2014. GeoDetector was applied to measure the determinant power (q statistic) of risk factors for TB among the elderly. RESULTS: The incidence of TB among the elderly exhibited geographical spatial heterogeneity, with a higher incidence in underdeveloped rural areas compared with that in urban areas. Hotspots of TB incidence risk among the elderly were mostly located in north-eastern and southern areas in the study region, far from metropolitan areas. Areas with low risk were distributed mainly in the Beijing-Tianjin metropolitan areas. Social-economic factors had a non-linear influence on elderly TB incidence, with the dominant factors among rural populations being income (q = 0.20) and medical conditions (q = 0.17). These factors had a non-linear interactive effect on the incidence of TB among the elderly, with medical conditions and the level of economic development having the strongest effect (q = 0.54). CONCLUSIONS: The findings explain spatio-temporal variation in TB incidence and risk determinants of elderly TB in the presence of disparities in social-economic development. High-risk zones were located mainly in rural areas, far from metropolitan centres. Medical conditions and the economic development level were significantly associated with elderly TB incidence, and these factors had a non-linear interactive effect on elderly TB incidence. The findings can help to optimize the allocation of health resources and to control TB transmission in the aging population in this region.

Velvet Antler Ameliorates Cardiac Function by Restoring Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats With Heart Failure After Myocardial Infarction.

Objective: Velvet antler (VA; cornu cervi pantotrichum), a well-known traditional Chinese medicine, has been shown to exert cardioprotective effects. The purpose of this study was to investigate the effect of VA on heart failure (HF) caused by ischemia-reperfusion, and explore its possible mechanism from the regulation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 alpha (SERCA2a). Methods: A rat model of HF was established by ligating the left anterior descending coronary artery of male Sprague-Dawley rats (n = 88). One week after surgery, VA (200, 400, or 800 mg/[kg day-1]) or enalapril (1 mg/[kg day-1]) was administered daily for the next 4 weeks. Heart function was detected by echocardiography and histopathological analysis. The serum BNP level was measured by ELISA, and the expression of SERCA2a, PLB, PLB-Ser16, and PKA was determined by western blotting. SERCA2a and PLB mRNA levels were determined by real-time quantitative PCR. Results: Compared with the sham group, cardiac function in the HF group, including the serum BNP level, heart mass index, myocardial collagen deposition, and left ventricular ejection fraction, was markedly reduced; however, these changes could be reversed by VA treatment. In addition, VA (200 mg/[kg·d-1]) inhibited the decrease of SERCA2a and PLB mRNA levels and SERCA2a, PLB, PLB-Ser16, and PKA protein expression and restored the activity of SERCA2a and PKA. Enalapril affected only PLB protein expression. Conclusion: VA can improve myocardial fibrosis and ventricular remodeling in rats, thereby helping to restore cardiac function. The underlying mechanism may be related to the upregulation of the expression and activation of PKA and PLB and the restoration of the expression and activity of SERCA2a.

Spatial heterogeneity of bacillary dysentery and the impact of temperature in the Beijing-Tianjin-Hebei region of China.

Previous studies indicate that the incidence of bacillary dysentery is closely related to meteorological factors. However, the impact of temperature and the spatial heterogeneity of the disease in regions of unbalanced socioeconomic development remains unclear. Therefore, this research collected data for 29,639 daily bacillary dysentery cases in children under 5 years of age, as well as the meteorological variables from China's Beijing-Tianjin-Hebei region, to analyze the spatial pattern of bacillary dysentery and reveal its nonlinear association with temperature. The SatScan method was employed first, to detect the spatial heterogeneity of the disease risk, and then the distributed lag nonlinear model (DLNM) was used to analyze the relationships between the daily minimum, mean, and maximum temperatures and bacillary dysentery in the stratified heterogeneous regions. The results indicated that bacillary dysentery incidence presented statistically significant spatial heterogeneity. The area of highest risk was found to be Beijing and its neighboring regions, which have high population densities. There was also a positive association between bacillary dysentery and temperature. Hotter temperatures were accompanied by higher relative risks. In the most likely spatial cluster region, the excess risk (ER) values for a 1°C rise in minimum, mean, and maximum temperatures above the median were 4.65%, 11.30%, and 19.21%, respectively. The effect of temperature on bacillary dysentery peaked at a lag of 3 to 4 days. The findings of this study will aid risk assessments and early warning systems for bacillary dysentery.

Spatiotemporal heterogeneity and its determinants of COVID-19 transmission in typical labor export provinces of China.

BACKGROUND: Previous studies have indicated that the risk of infectious disease spread is greatest in locations where a population has massive and convenient access to the epicenter of an outbreak. However, the spatiotemporal variations and risk determinants of COVID-19 in typical labor export regions of China remain unclear. Understanding the geographical distribution of the disease and the socio-economic factors affecting its transmission is critical for disease prevention and control. METHODS: A total of 2152 COVID-19 cases were reported from January 21 to February 24, 2020 across the 34 cities in Henan and Anhui. A Bayesian spatiotemporal hierarchy model was used to detect the spatiotemporal variations of the risk posed by COVID-19, and the GeoDetector q statistic was used to evaluate the determinant power of the potential influence factors. RESULTS: The risk posed by COVID-19 showed geographical spatiotemporal heterogeneity. Temporally, there was an outbreak period and control period. Spatially, there were high-risk regions and low-risk regions. The high-risk regions were mainly in the southwest areas adjacent to Hubei and cities that served as economic and traffic hubs, while the low-risk regions were mainly in western Henan and eastern Anhui, far away from the epicenter. The accessibility, local economic conditions, and medical infrastructure of Wuhan in Hubei province all played an important role in the spatiotemporal heterogeneity of COVID-19 transmission. The results indicated that the q statistics of the per capita GDP and the proportion of primary industry GDP were 0.47 and 0.47, respectively. The q statistic of the population flow from Wuhan was 0.33. In particular, the results showed that the q statistics for the interaction effects between population density and urbanization, population flow from Wuhan, per capita GDP, and the number of doctors were all greater than 0.8. CONCLUSIONS: COVID-19 showed significant spatiotemporal heterogeneity in the labor export regions of China. The high-risk regions were mainly located in areas adjacent to the epicenter as well as in big cities that served as traffic hubs. Population access to the epicenter, as well as local economic and medical conditions, played an important role in the interactive effects of the disease transmission.

Mechanism of SQQX Decoction's Protective Effect on SHR: A Serum Metabolomics-Based Analysis.

SangQiQingXuan (SQQX) decoction is a pharmaceutical preparation exerting good therapeutic efficacy on high blood pressure (BP) and has widely been accepted in primarily hypertensive patients as a herbal formula prescribed by Professor Li Huang from China-Japan Friendship Hospital according to her 30-year clinical experience. A previous study showed that SQQX could reduce BP by decreasing levels of many inflammatory factors such as transforming growth factor beta (TGFß) and elevating peroxisome proliferator activated receptor (PPAR) expression. However, a research focusing on SQQX's protection against HTN from a metabolomic perspective has never been done before. This study aimed to figure out the metabolic profiling variations due to oral administration of SQQX in spontaneous hypertensive rat (SHR) models and to find out the optimal dosage of SQQX. SHR in the intervention group orally received SQQX extract of three doses, namely, the low- (5.25 g/kg/d), middle- (10.5 g/kg/d), and high-dosage groups (21 g/kg/d) for 90 days. Rats were sacrificed at the end of the experiment, and their serum was collected for further examination. Serum metabolic profiling variations were analyzed using ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS). Results showed that dealing with SQQX remarkably decreased systolic blood pressure (SBP) of SHRs and the high-dosage group was with the best therapeutic effect where a total of 11 metabolites were markedly changed in contrast to the model group. Orthogonal partial least square discriminant analysis (OPLS-DA) score plot showed that the 5 groups of serum samples were divided into 5 categories, and the metabolic trajectory of the high-dosage SQQX group was inclined to move to the control group. Glycochenodeoxycholic acid, nicotinamide-N-oxide, and tryptophan betaine might be biomarkers that specifically marked the protective effects of SQQX against high BP mainly involving in cholesterol metabolism, primary bile acid biosynthesis, bile secretion, and nicotinate and nicotinamide metabolism. To conclude, SQQX has a protective effect on SHR, which may be partially correlated to restoration of perturbed metabolism in serum.

Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial.

BACKGROUND: Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. METHODS/DESIGN: In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle-brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. DISCUSSION: This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.

Velvet Antler Mobilizes Endothelial Progenitor Cells to Promote Angiogenesis and Repair Vascular Endothelial Injury in Rats Following Myocardial Infarction.

Objective: This investigation examined the effect of velvet antler (VA) on endothelial progenitor cells (EPCs) and the associated effects to promote angiogenesis and repair vascular endothelial injury in rats with myocardial infarction (MI). Methods: VA was analyzed by liquid chromatography-mass spectrometry. Male Sprague Dawley rats were randomly divided into four groups: sham, MI, VA, and VA + DAPT (gamma-secretase inhibitor IX, a specific blocker of the Notch signaling pathway) group. The rats underwent ligation of the left anterior descending coronary artery for the establishment of MI. Sham-operated rats were used as controls. Blood was taken from the orbital plexus on the first and third days after the operation, and all rats were euthanized on the 7th day after surgery. The blood samples were used to detect the contents of circulating endothelial progenitor cells (CEPCs) and vascular endothelial growth factor (VEGF). Echocardiography was used to test the cardiac function. Cardiac tissue was used for immunohistochemistry and electron microscope, and the marginal zone of the MI tissue was used for western blot and reverse transcription-quantitative polymerase chain reaction. Results: The number of basically qualitative metabolites is 445. Among them, there are 74 substances with relative content greater than 0.05%. VA increased the concentration of CEPCs and VEGF in serum, CD133 content and microvessel density (MVD), and protected the morphology of microvascular endothelial cells in the marginal area of MI at 7 days post-MI surgery. CEPCs and MVD in the VA +DAPT group were lower than those of VA group. VA increased the protein expressions of Jagged-1, Notch1, NICD and HES1, and the mRNA expressions of Hes1 and Hey2, while some of the effects could be suppressed by DAPT. Conclusion: These results suggest that VA promotes the mobilization of EPCs to promote angiogenesis and repair vascular endothelial cell damage in post-MI rats, and these effects may be due to activation of the Notch signal pathway.