Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.

Global Health ; History, 20th Century ; Humans ; Influenza A Virus, H2N2 Subtype ; genetics ; isolation & purification ; Influenza A Virus, H3N2 Subtype ; genetics ; isolation & purification ; Influenza, Human ; epidemiology ; history ; mortality ; virology

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Adolescent ; Child ; China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Mamastrovirus ; drug effects ; genetics ; pathogenicity ; Phylogeny ; Viral Proteins ; genetics

OBJECTIVETo study farm compost polluted water that may induce pharyngo-esophageal, gastric and liver carcinoma in chickens.

METHODS280 chickens were randomized into 4 groups: experiment group 100 chickens fed with compost water + NaNO(2) by stomach tube. The other 180 were evenly randomized into 3 control groups (60 each), fed with compost water, NaNO(2) and tap water in the same way. The farm compost was prepared with corn stalks, rice straws, excreta of men and livestock. The compost water, after being nitrosified and acidified, was fed through stomach tube 5 - 7.5 ml/session, twice a week. Besides, a solution consisting of the respective formula of each group added with 3 - 4 L water with pH adjusted to 3 - 4 by 1N HCL was given ad lib to all chickens in each group for 26.5 months.

RESULTSIn the experiment group, there were pharyngo-esophageal carcinoma 16 (16.3%), gastric adenocarcinoma 5 (10.4%) and liver carcinoma 3 (6.3%), in contrast to none in the 3 control groups, showing significant differences (P < 0.01, P < 0.01, P < 0.05).

CONCLUSIONSuccessful simulation of the layout of esophageal carcinoma high morbidity area and the mimic of chicken gastric fluid strongly support our compost etiological hypothesis that the nitrosified and acidified compost water are carcinogenic, very well causing esophageal, gastric and liver carcinoma.

Adenocarcinoma ; chemically induced ; pathology ; Animals ; Carcinoma, Squamous Cell ; chemically induced ; pathology ; Chickens ; Esophageal Neoplasms ; chemically induced ; pathology ; Feces ; Female ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Pharyngeal Neoplasms ; chemically induced ; pathology ; Random Allocation ; Sewage ; adverse effects ; Sodium Nitrite ; toxicity ; Stomach Neoplasms ; chemically induced ; pathology ; Water Pollution, Chemical ; adverse effects

OBJECTIVETo establish PEG10 transgenic mice model and study the effect of PEG10 transgene on tumor growth and metastasis in mice.

METHODSThe linearized expression element of pALB-PEG10, which contained mouse albumin promoter, structural gene of PEG10, and polyaenylation signal sequence, was microinjected into 3741 KM mouse fertilized ova. The manipulated embryos were then transplanted into the oviducts of 94 pseudopregnant recipient mice. All the newborn mice were screened by PCR to detect genomic DNA in tail tissue, then PEG10 mRNA and protein expression were detected by RT-PCR and western blot, respectively in the positive mice. Hepatoma cell H22 was subcutaneously inoculated into the right armpit of wild type mice and No.17, No.33 transgenic mice. Tumor size was measured every week. Mice were sacrificed on day 12 and then the tumors were exercised and weighted. Tumors and livers were fixed in formaldehyde and sectioned. The sections were stained with hematoxylin/eosin and examined under microscope. The expression of PEG10 protein was detected with immunohistochemistry method.

RESULTSAmong the 43 off-springs, 3 were positive for tail tissue PEG10 gene examination, PEG10 was successfully expressed in the liver of the randomly selected transgenic mouse. H22 tumor grew faster in all the transgenic mice than in wild type mice. The average size and weight of tumors between the transgenic mice and wild type mice were significantly different (P < 0.05). Most tumors in the transgenic mice invaded the surrounding tissues and showed liver metastasis, PEG10 protein was expressed in liver. In contrast, nearly all the tumors in wild type mice were capsulized and PEG10 was not expressed in liver.

CONCLUSIONOur results showed that the PEG10 gene could be expressed in the liver of the transgenic mice. PEG10 promotes growth, invasion, and metastasis of transplanted H22 tumors in mice.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Genetic Vectors ; Humans ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Mice ; Mice, Transgenic ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transgenes ; Xenograft Model Antitumor Assays

Cynomolgus monkeys as nonhuman primates are valuable animal models because they have a high level of human gene homology. There are many reference values for hematology and biochemistry of Cynomolgus monkeys that are needed for proper clinical diagnosis and biomedical research conduct. The body weight information and blood type are also key success factors in allogeneic or xenogeneic models. Moreover, the biological parameters could be different according to the origin of the Cynomolgus monkey. However, there are limited references provided, especially of Cambodia origin. In this study, we measured average body weight of 2,518 Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119 males, and determined blood types in 642 monkeys with Cambodia origin. The average body weight of male Cynomolgus monkeys were 2.56±0.345 kg and female group was 2.43±0.330 kg at the age from 2 to 3 years. The male group showed relatively sharp increased average body weight from the 3 to 4 age period compared to the female group. In hematology and biochemistry, it was found that most of the data was similar when compared to other references even though some results showed differences. The ABO blood type result showed that type A, B, AB, and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood type in this facility was B and AB. These biological background references of Cambodia origin could be used to provide important information to researchers who are using them in their biomedical research.
Biochemistry* ; Body Weight ; Cambodia* ; Diagnosis ; Female ; Haplorhini ; Hematology* ; Humans ; Macaca fascicularis* ; Male ; Models, Animal ; Primates ; Reference Values*

Objective To discuss the risk factors on short-term prognosis after kidney transplantation from donors after cardiac death (DCD). Methods We retrospectively analyzed the information of donors and recipients who performed DCD donor kidney transplantation in our center between January 2011 and August 2015, including 64 donors and 95 recipients. Also, we analyzed the potential relationship among donors' clinical characteristics and the early recovery of graft function, including the incidence of delayed graft function(DGF)and the serum creatinine (SCr) on the 90th day, and infection rate after kidney transplantation.Results We found that when donors had the factors of WIT>10 min, urine volume<100 ml/h, SBP≤100 mmHg or a history of CPR, the incidence of recipients' DGF were 55.6%,73.3%,62.5%,77.8% respectively with a significant difference. Recipients would have more chance to be infected if donors have the following characteristics: male, older than 50 years, died of cerebral hemorrhage which was caused by cardiovascular diseases, WIT>30 min, treated in ICU for more than 10 days or infection. Conclusions Nowadays, DCD has become the main graft source in Chinese kidney transplantation. This research indicates that the donors' factors may affect the recovery of graft function and the incidence of infection after kidney transplantation to some extent.By evaluating rigorously and preserving quality of renal grafts carefully, DCD would become more safe and valid.

Objective To observe the effect of low frequency repetitive transcranial magnetic stimulation at uninjured side on memory and quality of life in patients with traumatic brain injury. Methods From September, 2013 to June, 2015, 60 cases of memory impairment af-ter traumatic brain injury were randomly divided into control group (n=30) and observation group (n=30). The control group was given neu-rosurgical conventional treatment;the observation group was given low frequency repetitive transcranial magnetic stimulation in addition, for four weeks. The scores of Rivermead Behavior Memory Test (RBMT) and the World Health Organization Quality of Life-BREF (WHO-QOL-BREF) were observed before and after treatment in both groups. Results After treatment, there was no significant difference in the RBMT score in the control group (t=1.233, P=0.223);the RBMT score increased in the observation group (t=2.186, P=0.033);and there was no significant difference between two groups (t=1.133, P=0.262). After treatment, the WHOQOL-BREF score increased in physical health in the control group (t=5.606, P<0.001), while it increased in the physical, psychological health, and environment in the observation group (t>2.879, P<0.01), which were higher in the observation group than in the control group (t>2.095, P<0.05). There was no significant differ-ence in the social relationship between two groups (t=0.508, P=0.614). Conclusion Low frequency repetitive transcranial magnetic stimula-tion at uninjured side could improve the memory ability and quality of life for patients with traumatic brain injury.

Objective:To observe the efficacy and safety of Iguratimod in reducing the level of panel reactive antibodies in renal transplant recipients.Methods:The clinical data of 35 patients with PRA-positive renal transplant recipients were retrospectively analyzed. All recipients were treated with Iguratimod for PRA-positive. The changes in PRA levels before and after treatment and the adverse events were observed.Results:Of the 35 recipients, 4 of them were discontinued due to pulmonary infection, and 2 patients were discontinued during the observation period. 3 patients were lost to follow-up. A total of 26 recipients were included. When Iguratimod was taken to 9 months, the PRA was reviewed. 71.5 % of the 207 sites showed a downward trend, 69.9 % of the 107 class I sites and 75.9 % of the 41 class II site showed a downward trend, and there was no difference in renal function before and after treatment. There were no significant changes in blood routine, liver function, blood lipids, and blood glucose. There were no other adverse events.Conclusions:Iguratimod can effectively reduce the level of PRA in renal transplant recipients with less adverse events.