Safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers: a randomized, placebo-controlled, double-blind study.

The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18-50 years. Thirty subjects received single subcutaneous injection of 0.3 µg/kg, 1.0 µg/kg, 2.0 µg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3-2.0 µg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 µg/kg or placebo groups. The mean PLT of subjects in the 1.0 µg/kg and 2.0 µg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3-2.0 µg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 µg/kg.P lain l anguage s ummaryWhat is the context?● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding.● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices.What is new?● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China).● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection.● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects.What is the impact?● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.

GSA-Human: Genome Sequence Archive for Human.

The Genome Sequence Archive for Human (GSA-Human) is a data repository specialized for human genetic related data derived from biomedical researches, and also supports the data collection and management of National Key Research and Development Projects. GSA-Human has a data security management strategy according to the national regulations of human genetic resources. It provides two different models of data access: Open-access and Controlled-access. Open-access data are universally and freely accessible for global researchers, while Controlled-access ensures that data are accessed only by authorized users with the permission of the Data Access Committee (DAC). Till July 2021, GSA-Human has housed more than 5.27 PB of data from 750 datasets.

An online coronavirus analysis platform from the National Genomics Data Center.

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).

The 2019 novel coronavirus resource.

An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.

[GSA: Genome Sequence Archive].

The Genome Sequence Archive (GSA), a new data repository for raw sequence reads in China, has been developed in compliance with the International Nucleotide Sequence Database Collaboration (INSDC) standards. It supports data generated from a variety of sequencing platforms ranging from Sanger sequencing to single-cell sequencing and provides data storing and sharing services freely for worldwide scientific communities. Since it went online in late 2015, GSA has archived more than 500 TB data and been acknowledged by many high-profile journals, including Cell, Nature, PNAS, GPB, etc. Focusing on omics data submission, storing and sharing typically for Chinese users, GSA promotes the initiative of the National Bioinformatics Center of China. This paper introduces the specifies of GSA as data collection, curation, management and exchange to facilitate users to understand and use GSA database.

The complete mitochondrial genome of Anser indicus (Aves, Anseriformes, Anatidae).

The bar-headed goose is known one of the world's highest-flying birds. In this study, the complete mitochondrial genome of Anser indicus (16,728 bp in length) was sequenced. Similar to the typical mtDNA of other vertebrates, goose mtDNA contained 37 genes (13 protein-coding genes, 2 rRNA genes and 22 tRNA genes) and a non-coding region (D-loop). The characteristics of the mitochondrial genome were analyzed in detail. We deduce that ND5 may be a major gene required for adaptation to high-altitude flight. The complete mitochondrial genome sequence of A. indicus obtained will be useful for phylogenetics, and biological characteristics.

Preparation and pharmacodynamic evaluation of naringenin lyophilized liposome.

OBJECTIVE: To prepare the lyophilized powder of naringenin liposome and investigate its pharmacodynamics in rat models of acute lung injury (ALI). METHODS: Naringenin liposome was prepared by ethanol injection method and then its quality was evaluated. Also, the related characteristics was evaluated by adding mannitol (5%,W/V) as lyoprotectant to be freeze-dried. The rat ALI models were established by inhaling lipopolysaccharide (LPS) (5 mg/kg). Totally 48 female Sprague-Dawley rats were randomly divided into six groups:control group(A), LPS group(B), LPS+naringenin group(C), LPS+lyophilized liposome group(D), LPS+dexamethasone group(E), and LPS+blank liposome group(F), with 8 rats in each group. Lung wet/dry weight ratio was calculated, and the histopathological morphologies were observed under the light microscope. RESULTS: The encapsulation efficiency of the prepared liposome was (82.44 ± 0.98)%, the average particle size was (133 ± 11)nm, and the Zeta potential was (-35.9 ± 5)mV. The angle of repose of lyophilized powder was 36℃ and the bulk density was 0.3 g/ml. Compared with the group A, the lung tissues from groups B to F showed different remarkable histopathological changes under a light microscope, including infiltration of inflammatory cells, capillary congestion, hemorrhage, and marked thickening of the alveolar wall,among which group B and F changed the most significant, followed by group C, whereas groups D and E were the lightest. The wet/dry weight ratios increased in groups B to F compared with group A in some degree, and the increase of the lung wet/dry weight ratio in group D and E was significantly lower than in group B(P=0.0012, P=0.0018). CONCLUSION: The technology of preparing naringenin liposome by ethanol injection is simple and feasible, and lyophilized powder has an obvious therapeutic effect on ALI.

DoGSD: the dog and wolf genome SNP database.

The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼ 19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.

The CD8α gene in duck (Anatidae): cloning, characterization, and expression during viral infection.

Cluster of differentiation 8 alpha (CD8α) is critical for cell-mediated immune defense and T-cell development. Although CD8α sequences have been reported for several species, very little is known about CD8α in ducks. To elucidate the mechanisms involved in the innate and adaptive immune responses of ducks, we cloned CD8α coding sequences from domestic, Muscovy, Mallard, and Spotbill ducks using reverse transcription polymerase chain reaction (RT-PCR). Each sequence consisted of 714 nucleotides and encoded a signal peptide, an IgV-like domain, a stalk region, a transmembrane region, and a cytoplasmic tail. We identified 58 nucleotide differences and 37 amino acid differences among the four types of duck; of these, 53 nucleotide and 33 amino acid differences were between Muscovy ducks and the other duck species. The CD8α cDNA sequence from domestic duck consisted of a 61-nucleotide 5' untranslated region (UTR), a 714-nucleotide open reading frame, and an 849-nucleotide 3' UTR. Multiple sequence alignments showed that the amino acid sequence of CD8α is conserved in vertebrates. RT-PCR revealed that expression of CD8α mRNA of domestic ducks was highest in the thymus and very low in the kidney, cerebrum, cerebellum, and muscle. Immunohistochemical analyses detected CD8α on the splenic corpuscle and periarterial lymphatic sheath of the spleen. CD8α mRNA in domestic ducklings was initially up-regulated, and then down-regulated, in the thymus, spleen, and liver after treatment with duck hepatitis virus type I (DHV-1) or the immunostimulant polyriboinosinic polyribocytidylic acid (poly I:C).

[Preparation of Baicalein Liposome-Lyophilized Powder and Its Pharmacokinetics Study].

OBJECTIVE: To prepare baicalein liposome-lyophilized powder, and to investigate the particle size distribution, encapsulation efficiency, stability, in vitro release and in vivo pharmacokirietics in rats. METHODs: Baicalein liposome was prepared by the ethanol injection, the encapsulation efficiency was measured by column chromatography, glucose, lactose and mannitol were selected as lyoprotectants. Pharmacokinetics study in rats was carried out by oral administration and analysis of rats pharmacokinetic parameters. RESULTS: The baicalein liposomes were spherical, the mean diameter was (93.1 ± 11.2) nm, PDI was 0.258, the encapsulation efficiency was (83.9 ± 0.4)%. In vitro release test results showed that it had a significant slow-release effect, freeze-dried mannitol for the best protective agent. The pharmacokinetic parameters of baicalein liposomes and solution were as follows: AUC(0 --> 24 (129.04 ± 12.73) µg/mL x h and (73.31 ± 9.34) µg/mL x h; C(max) (15.07 ± 3.13) µg/mL and (9.38 ± 2.42) µg/mL; T(max) 1 and 1.5 h. CONCLUSION: Baicalein liposome has the higher entrapment efficiency and the smaller particle size. In vitro studies show that baicalein liposome has a slow-release effect and can significantly improve the bioavailability in rats.

Molecular cloning and expression analysis of ferritin, heavy polypeptide 1 gene from duck (Anas platyrhynchos).

H-ferritin is a core subunit of the iron storage protein ferritin, and is related to the pathogenesis of malignant diseases. A differential expressed sequence tag of the ferritin, heavy polypeptide 1 gene (FTH1) was obtained from our previously constructed suppression subtractive cDNA library from 3-day-old ducklings challenged with duck hepatitis virus type I (DHV-1). The expression and function of FTH1 in immune defense against infection remains largely unknown in ducks. In this study, the full-length duFTH1 cDNA was obtained using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. It consisted of 153 basepairs (bp) 5'untranslated region (UTR), 183 bp 3'UTR, and 546 bp open reading frame that encodes a single protein of 181 amino acid residues. duFTH1 shares high similarity with FTH1 genes from other vertebrates. The amino acid sequence possesses the conserved domain of typical ferritin H subunits, including seven metal ligands in the ferroxidase center, one iron binding region signature, and a potential bio-mineralization residue (Thy(29)). Moreover, in agreement with a previously reported ferritin H subunit, we identified an iron response element in the 5'UTR. RT-PCR analyses revealed duFTH1 mRNA is widely expressed in various tissues. Real-time quantitative polymerase chain reaction analyses suggested that duFTH1 mRNA is significantly up-regulated in the liver after DHV-1 injection or polyriboinosinic polyribocytidylic acid (polyI:C) treatment, reaching a peak 4 h post-infection, and dropping progressively and returning to normal after 24 h. Our findings suggest that duFTH1 functions as an iron chelating protein subunit in duck and contributes to the innate immune responses against viral infections.

Identification and differential expression of microRNAs in ovaries of laying and Broody geese (Anser cygnoides) by Solexa sequencing.

BACKGROUND: Recent functional studies have demonstrated that the microRNAs (miRNAs) play critical roles in ovarian gonadal development, steroidogenesis, apoptosis, and ovulation in mammals. However, little is known about the involvement of miRNAs in the ovarian function of fowl. The goose (Anas cygnoides) is a commercially important food that is cultivated widely in China but the goose industry has been hampered by high broodiness and poor egg laying performance, which are influenced by ovarian function. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the miRNA transcriptomes of ovaries from laying and broody geese were profiled using Solexa deep sequencing and bioinformatics was used to determine differential expression of the miRNAs. As a result, 11,350,396 and 9,890,887 clean reads were obtained in laying and broodiness goose, respectively, and 1,328 conserved known miRNAs and 22 novel potential miRNA candidates were identified. A total of 353 conserved microRNAs were significantly differentially expressed between laying and broody ovaries. Compared with miRNA expression in the laying ovary, 127 miRNAs were up-regulated and 126 miRNAs were down-regulated in the ovary of broody birds. A subset of the differentially expressed miRNAs (G-miR-320, G-miR-202, G-miR-146, and G-miR-143*) were validated using real-time quantitative PCR. In addition, 130,458 annotated mRNA transcripts were identified as putative target genes. Gene ontology annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis suggested that the differentially expressed miRNAs are involved in ovarian function, including hormone secretion, reproduction processes and so on. CONCLUSIONS: The present study provides the first global miRNA transcriptome data in A. cygnoides and identifies novel and known miRNAs that are differentially expressed between the ovaries of laying and broody geese. These findings contribute to our understanding of the functional involvement of miRNAs in the broody period of goose.

DNA methylation and regulation of the CD8A after duck hepatitis virus type 1 infection.

BACKGROUND: Cluster of differentiation 8 (CD8) is expressed in cytotoxic T cells, where it functions as a co-receptor for the T-cell receptor by binding to major histocompatibility complex class I (MHCI) proteins, which present peptides on the cell surface. CD8A is critical for cell-mediated immune defense and T-cell development. CD8A transcription is controlled by several cis-acting elements and trans-acting elements and is also regulated by DNA methylation. However, the epigenetic regulation of CD8A in the duck and its relationship with virus infection are still unclear. RESULTS: We investigated the epigenetic transcriptional regulatory mechanisms, such as DNA methylation, for the expression of the CD8A and further evaluated the contribution of such epigenetic regulatory mechanisms to DHV-I infection in the duck. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed the highest level of CD8A expression to be in the thymus, followed by the lungs, spleen, and liver, and the levels of CD8A expression were very low in the kidney, cerebrum, cerebellum, and muscle in the duck. RT-qPCR also demonstrated that the CD8A mRNA was down-regulated significantly in morbid ducklings treated with DHV-1 and up-regulated significantly in non-morbid ducklings in all the tissues tested. In addition, hypermethylation of CD8A was detected in the morbid ducklings, whereas relatively low methylation of CD8A was evident in the non-morbid ducklings. The CD8A mRNA level was negatively associated with the CpG methylation level of CD8A and global methylation status. CONCLUSIONS: We concluded that the mRNA level of the CD8A was negatively associated with the CpG methylation level of CD8A and global methylation status in the duck, suggesting that the hypermethylation of CD8A may be associated with DHV-1 infection. The first two CpG sites of the CD8A promoter region could be considered as epigenetic biomarkers for resistance breeding against duckling hepatitis disease in the duck.

Identification and expression analysis of the leukocyte cell-derived chemotaxin-2 (LECT2) gene in duck (Anas platyrhynchos).

Leukocyte cell-derived chemotaxin 2 (LECT2), first identified as a chemotactic factor, is involved in the regulation of liver regeneration, carcinogenesis, and natural killer T-cell homeostasis in mammals. The function of LECT2 in the duck remains unclear, however. A suppression subtractive cDNA library was constructed from the livers of 3-day-old ducklings treated with duck hepatitis virus type I (DHV-1). A total of 66 expressed sequence tags (ESTs) were identified in the libraries. Among the novel gene fragments identified was the LECT2 gene. Full-length duck LECT2 (duLECT2) complementary DNA (cDNA) was obtained using the reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of the cDNA ends (RACE). The cDNA consisted of a 50 nucleotide 5' untranslated region (UTR), an 84 nucleotide 3' UTR, and a 1020 nucleotide open reading frame encoding a single protein of 339 amino acids. In agreement with a previously reported LECT2 sequence, the predicted amino acid sequence contains characteristic phosphorylation and N-glycosylation sites. DuLECT2 is highly similar to LECT2 genes from other vertebrates. Phylogenetic analysis demonstrated that the LECT2 gene has been highly conserved throughout vertebrate evolution. RT-PCR analyses revealed that duLECT2 mRNA is widely expressed in healthy tissues. They also showed that duLECT2 mRNA is significantly up-regulated in the liver and spleen following injection with DHV-1 or polyriboinosinic polyribocytidylic acid (poly I:C), peaking 4 or 12h post-challenge in the liver and spleen, respectively, and afterwards gradually returning to normal. Our findings suggest that duLECT2 contributes to the innate immune response against viral infections.

The genomics of selection in dogs and the parallel evolution between dogs and humans.

The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.

ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.

N(6)-methyladenosine (m(6)A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. The discovery of this RNA demethylase strongly suggests that the reversible m(6)A modification has fundamental and broad functions in mammalian cells.

Comparative genomic analysis of growth hormone gene in geese.

To explore the mutation characteristic of growth hormone (GH) gene in geese, all the exons and introns of the gene were amplified by 20 pairs of primers, and then single nucleotide polymorphisms (SNPs) were detected by single strand conformation polymorphism (SSCP) and subsequently confirmed by sequencing. There were six SNPs per 1000 nucleotides in exons compared to two SNPs per 1000 nucleotides in intron regions. The variant in exons contained only one non-synonymous mutation and three synonymous mutations. The results show that its sequence identity with chicken and duck were 77.54% and 92.38%, respectively, which may be concluded that the GH gene was highly conservative in phylogenesis, although there were differences between waterfowls and chicken in their evolution process.

Effect of traditional and integrative regimens on quality of life and early renal impairment in elderly patients with isolated systolic hypertension.

OBJECTIVE: To observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH). METHODS: A multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment. RESULTS: After treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05). CONCLUSIONS: Chinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.

Traditional Chinese versus integrative treatment in elderly patients with isolated systolic hypertension: a multicenter, randomized, double-blind controlled trial.

BACKGROUND: Isolated systolic hypertension (ISH) is a common disease in elderly people, threatening their health. Traditional Chinese medicine (TCM) treatment or integrative treatment had advantages in improving quality of life and protecting target organs, but need to be proved by large evidence-based researches. OBJECTIVE: To observe the effects of TCM treatment (Jiangya Capsule) or integrative treatment (combination of Jiangya Capsule and nimodipine) on blood pressure and vasoactive agents, and their safety in elderly ISH patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A multicenter, randomized, double-blind controlled trial was adopted. A total of 270 elderly ISH patients recruited from Xiyuan Hospital, and TCM Hospital and Community Health Service Centers of Yanqing County of Beijing were randomly divided into 3 groups: TCM group (Jiangya Capsule plus nimodipine simulation, 90 cases), integrative group (Jiangya Capsule plus nimodipine, 90 cases) and Western medicine (WM) group (nimodipine plus Jiangya Capsule simulation, 90 cases). They were all treated for 4 weeks. MAIN OUTCOME MEASURES: Before and after 4-week treatment, office blood pressure, 24-hour ambulatory blood pressure, serum nitric oxide (NO), and plasma endothelin-1 (ET-1), thromboxane B2 (TXB2) and 6-keto-prostaglandin 1alpha (6-keto-PGF1alpha) were detected, and safety evaluation was conducted. RESULTS: After 4-week treatment, 5 patients in TCM group were lost to follow-up and another 5 patients were excluded, and 80 patients finished the trial; 7 patients in integrative group were lost to follow-up and another 7 patients were excluded, and 76 patients finished the trial; 2 patients in WM group were lost to follow-up and another 3 patients were excluded, and 85 patients finished the trial. After treatment, systolic blood pressure (SBP) decreased in each group (P<0.05), and integrative treatment was superior to TCM or WM treatment in decreasing SBP (P<0.05). Twenty-four hour average SBP and day average SBP decreased significantly in each group, and night average SBP decreased in integrative group, and integrative treatment was superior to TCM or WM treatment in decreasing day average SBP. Serum NO and plasma 6-keto-PGF1alpha levels were elevated and plasma ET-1 and TXB(2) levels were reduced after treatment, and integrative treatment was superior to TCM or WM treatment in reducing plasma TXB(2) level. CONCLUSION: TCM treatment or integrative treatment has affirmative effects and safety in treating elderly ISH patients, and integrative treatment has superiority in improving some indexes, and deserves further study.