OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives. METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480. RESULTS These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)for the simultaneous determination of gefitinib,erlotinib,nillotinib and imatinib plasma concentrations and analyze the results.Methods The plasma samples were treated with acetonitrile precipitation and separated by Diamonsil C18 column(150 mm ×4.6 mm,3.5 μm)with mobile phase of 0.1％formic acid water(A)-0.1％formic acid acetonitrile(B).The flow rate of gradient elution was 0.7 mL·min-1,and the column temperature was 40 ℃ and the injection volume was 3 μL.Using arotinib as the internal standard,the scanning was carried out by using electrospray ionization source in positive ionization mode with multi-reaction monitoring.The specificity,standard curve,lower limit of quantitation,precision,accuracy,recovery rate,matrix effect and stability of the method were investigated.The concentrations of imatinib and erlotinib in 20 patients with chronic myelogenous leukemia(CML)and gefitinib and erlotinib in 3 patients with non-small cell lung cancer were measured.Results The standard curves of the four drugs were as follows,gefitinib:y=2.536 × 10-3x+9.362 × 10-3(linear range 20-2 000 ng·mL-1,R2=0.996 6);erlotinib:y=3.575× 10-3x+7.406 × 10-3(linear range 50-5 000 ng·mL-1,R2=0.994 9);nilotinib:y=1.945 x 10-3x+0.015 643(linear range 50-5 000 ng·mL-1,R2=0.990 6);imatinib:y=4.56 x 10-3x+0.010 451(linear range 100～104 ng·mL-1,R2=0.9963).RSD of intra-day and inter-day were less than 10％,and the accuracy ranged from 90％to 110％,and the recovery rates were 91.35％to 98.93％(RSD＜10％);the matrix effect ranged from 91.64％to 107.50％(RSD＜10％).Determination of 23 patients showed that the blood concentration of nilotinib ranged from 623.76 to 2 934.13 ng·mL-1,and the blood concentration of imatinib ranged from 757.77 to 2 637.71 ng·mL-1,and the blood concentration of gefitinib ranged from 214.76 to 387.40 ng·mL-1.The serum concentration of erlotinib was 569.57 ng·mL-1.Conclusion The method of this research is simple,fast,sensitive and dedicated,which can be monitored by the concentration of clinical blood.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Aim To investigate the effect of Dahuang Tangluo pills(DHTL)on NOD-like receptor protein 3(NLRP3)/cysteine aspartate proteolytic enzyme-1(caspase-1)/apodermic D(GSDMD)pathway-media-ted pyroptosis in db/db mice with diabetic kidney dis-ease(DKD)and the underlying mechanism.Methods Eight db/m mice were selected as control group,and forty db/db mice were randomly divided into mod-el group,low dose group,medium dose group,high dose group and dapagliflozin group,with eight mice in each group.The control group and model group were given equal volume normal saline intragastric adminis-tration,the low,medium and high dose groups were given DHTL solution of 0.9,1.8 and 3.6 mg·kg-1,respectively,and the dapagliflozin group was given dapagliflozin tablet solution of 1.5 mg·kg-1,and the six groups were given intragastric administration once a day for 10 weeks.The body weight of mice was meas-ured daily and the dose was adjusted during adminis-tration.Fasting blood glucose(FBG)and body weight were measured after administration.The levels of 24-hour urinary total protein(24h-UTP),blood creatinine(Scr)and urea nitrogen(BUN)were measured by au-tomatic biochemical analyzer.The levels of interleukin-1 β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in re-nal tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining.The DNA damage in mouse kid-ney tissue was observed using in situ end labeling(TUNEL)staining.The mRNA and protein expres-sions of NLRP3,caspase-1 and GSDMD in mouse kid-ney tissues were detected by Real-time quantitative PCR and Western blot.Results Compared with the control group,FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in the model group significantly increased(P＜0.01).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in mouse kidney tis-sues significantly increased(P＜0.01).Compared with the model group,the levels of FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in each administration group significantly decreased(P＜0.05).The patho-logical morphology of renal tissue was improved in dif-ferent degrees,and the number of positive cells in re-nal tissue was significantly reduced(P＜0.05).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in renal tissue of mice in high and medi-um dose of DHTL and dapagliflozin group significantly decreased(P＜0.05).Conclusions DHTL can im-prove the renal injury of DKD,and its mechanism may be through the regulation of NLRP3/caspase-1/GSD-MD pathway to inhibit pyroptosis and relieve the in-flammatory response of DKD mice.

Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.
Asia/epidemiology* ; Global Burden of Disease ; Humans ; Incidence ; Pancreatic Neoplasms/epidemiology* ; Risk Factors

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic

Objective To analyze the research status,hotspots,and frontiers of atherosclerosis genomics from 2010 to 2019.Methods CiteSpace software was used to conduct data statistics and visual analysis on countries,institutions,authors,journals,co-cited papers,and keywords of the related papers published in the Web of Science from 2010 to 2019.Results A total of 1021 papers in English were included,and the annual number of publications generally showed an upward trend.The knowledge base in the research of atherosclerosis mostly focused on the genetic risk sites and biomarkers for coronary artery diseases such as coronary heart disease,myocardial infarction,and dyslipidemia.The related journals mainly involved the fields of molecular biology,biology,genetics,immunology,medicine,pharmacy,and clinical medicine.The latest research in atherosclerosis concentrated on genome-wide association study,DNA methylation,microRNA,messenger RNA and so on.The research frontiers involved long noncoding RNA,DNA methylation,and immune metabolism.Conclusion The studies in atherosclerotic genomics have gradually increased.
Atherosclerosis/genetics* ; Bibliometrics ; Biomarkers ; Genome-Wide Association Study ; Genomics ; Humans

OBJECTIVE: To establish the aGVHD mouse model，and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice. METHODS: C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. The mice in the two groups containing GSI were intraperitoneally injected with GSI at 5 μmol/kg on day 1, 2, and 3 after transplantation with DMSO as a control. The general conditions, survival time and hematopoietic recovery of mice were observed, cytokines were detected by ELISA, and histopathological changes were detected by immunohistochemistry. The effects of low-dose GSI combined with BMSC on hematopoietic reconstruction and aGVHD development after allo-BMT were investigated. RESULTS: The survival rate of the mice in BM+SC+BMSC+GSI combination group was 80% during the observation period, which was significantly higher than that in the other groups; the incidence of aGVHD was reduced in the BMSC GSI or their combination groups after 21 days of transplantation. GSI could partly promote the recovery of leukocytes, and show no significant delayed effect on the recovery platelets. Moreover, the level of Th1 cytokines (IFN-γ) in BM+SC+BMSC+GSI combined group was lower than that in BM+SC+GSI group (P<0.01), the level of Th2 cytokines (IL-4) in the combination group was higher than that in BM+SC+GSI group (P<0.01), also the level of IL-17 was significantly lower than that in the corresponding control group (P<0.001). CONCLUSION Low dose GSI combined with BMSC can promote hematopoietic reconstruction and regulate cytokines secretion including IFN-γ, IL-4 and IL-17. GSI combined with BMSC achieve the goal of synergistically inhibiting the occurrence and progression of aGVHD.
Amyloid Precursor Protein Secretases ; Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL

ObjectiveGut microbiota plays an important role in Parkinson′s disease, but the mechanisms behind this remain unknown. This study aims to investigate the characteristics of intestinal microbiota in patients with Parkinson′s disease, and to study the changes of intestinal Prevotella_copri and their role in this disease.Methods The study was carried out in 46 patients with Parkinson′s disease and their spouses. The spouse has been living with the patient for a long time, not suffering from any disease. Fecal samples from all subjects were collected using sterile containers. The bacterial DNA was extracted on ice following the Kit protocol. We used the BGISEQ-500 high-throughput sequencing platform to conduct metagenomic shotgun sequencing, to explore the changes of patients′ intestinal microbiota through bioinformatics, and to analyze the function and role of differential microorganisms in disease.ResultsCompared to healthy spouse, the gut microbiota of patients with Parkinson′s disease was significantly changed, which was characterized by decreased Prevotellaceae and Prevotella_copri, but by significantly elevated Bacteroides_stercoris and Escherichia_coli. Prevotella_copri was decreased with age increasing. The correlation analysis showed a significantly negative correlation between the abundance of Prevotella_copri and age, H-Ystage, UPDR total score, and UPDRS Ⅲ score. Results of the random forest model indicated five items including Prevotella_copri had good predictive value for the disease. The functional analysis stated pathways associated with super-pathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation. The glucose-1-phosphate degradation and methyl phosphonate degradation significantly increased in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation, and pyrimidine deoxyribonucleosides salvage significantly decreased. Pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle, and guanosine ribonucleotides de novo biosynthesis.ConclusionStructural composition and metabolic functions of gut microbiota were significantly changed in patients with Parkinson′s disease. Prevotella_copri plays an important role in the occurrence and progression of the disease and can be used as a potential biomarker for Parkinson′s disease.