Denys-Drash Syndrome ; diagnosis ; Humans ; Infant ; Male

Occupational Medicine ; education

OBJECTIVE: To assess the patterns of linkage disequilibrium (LD) of 16 STR loci on X chromo- some and investigate the genetic stability. METHODS: Genomic DNA samples extracted from blood stains from 500 unrelated individuals and 885 lineage members from Eastern Chinese Han population were genotyped through multiplex amplification using IDtyperX-16 kit by our independent research followed by capillary electrophoresis. LD was assessed by PowerMarker v3.25 software and mutation rate of every locus was analyzed. RESULTS: LD were not found at the 16 X-STR loci. Allele mutations were observed at 10 loci. Among them, mutation rates of DXS6809 and DXS7132 were both up to 0.0048. CONCLUSION When the 16 X-STR loci included in IDtyperX-16 kit were used for parentage testing, product princi- ples can be applied to calculate the likelihood, but mutation should be taken into consideration in the case that the genotypes do not meet the genetic law (especially at DXS6809 and DXS7132).
Alleles ; Asian People/genetics* ; Blood Stains ; China ; Chromosomes, Human, X/genetics* ; Electrophoresis, Capillary ; Female ; Forensic Genetics/methods* ; Gene Frequency ; Genetic Loci/genetics* ; Genotype ; Humans ; Linkage Disequilibrium/genetics* ; Microsatellite Repeats/genetics* ; Multiplex Polymerase Chain Reaction ; Mutation ; Mutation Rate

Objective To investigate the therapeutic effect of intracerebral transplantation of mesenchymal stem cells(MSCs) derived from human umbilical cord blood(UCB) on hypoxic-ischemic brain damage(HIBD) in neonatal rat.Methods Twenty samples of human UCB were collected from healthy full-term newborns.MSCs were isolated from human UCB by density gradient centrifugation and purified by adhere cell selection method.For transplantation,P3 human UCB-derived MSCs were labeled by the 5-bromo-2-deoxyuridine (BrdU).Thirty SD rats of 7 d were built for neonatal HIBD model.One rat died and others were divided into transplant group(n=18) and control group(n=11).At the third day after building models,human UCB-derived MSCs were injected into left cortex in transplant group,while PBS of the same volume was injected into the same site in control group at the same time.The seventh day after transplantation,6 rats of transplant group were sacrificed to prepare brain tissue sections.The survival,migration and differentiation of the transplanted cells were investigated by brain tissue immunohistochemical analysis,and nervous function of 2 groups were evaluated by modified neurological severity score(mNSS) on the first,7th,14th,21th and 28th day after transplantation.Results MSCs were isolated from 5 of 20 human UCB samples.Immunocytochemical analysis of brain tissue showed that the transplanted human UCB-derived MSCs could survive and migrate around by the center of transplant site.There were (12.67?2.73)% of MSCs differentiated into astrocyte-like cells.mNSS showed that the score of transplant group was lower than that of control group on the first,7th,14th,21th and 28th day,and the differences of score points between 2 groups on the 14th,21th and 28thday were statistically significant(Pa

Objective:To examine the expression of nitric oxide synthase(NOS),the content of nitric oxide and blood flow in nasal mucosa of allergic rhinitis guinea pigs,so as to further investigate the mechanism of allergic rhinitis.Methods:One hundred and twenty guinea pigs were randomly divided into control group(injected with normal saline)and allergic group(nasal challenge with egg albumin).The guinea pigs were executed before and immediately,24,48,72 h after the last nasal challenge;the expression of endothelial nitric oxide synthase(eNOS)and inducible nitric oxide synthase(iNOS)and the content of nitric oxide were examined in mucosa tissues.The blood flow in the nasal mucosa was determined in animals before execution.Linear regression correlation was used to analyze the relationship between the nitric oxide content and blood flow in nasal mucosa.Results:The immunostaining for iNOS in surface epithelium of allergic rhinitis guinea pigs was markedly stronger than that of normal guinea pigs at all time points(P

AIM: To observe the effects of different interval administration of exogenous brain derived neurotrophic factor (BDNF) on hypoxic-ischemic encephalopathy in neonatal rats. METHODS: BDNF (0.5 μg) was microinjected intracerebroventricularly at 0, 1 and 4 h after the hypoxic-ischemic encephalopathy in 7 d neonatal Sprague-Dawley rats undergone by ligation of left common carotid artery followed by a 2.5 h inhalation of humidified 8% 02 + 92% N2 at 37°C immediately after the injury, respectively. Changes of brain edema, levels of malondialehyde (MDA) and neuronal apoptosis at the left cortex and hippocampus were investigated 24 h after the injury. RESULTS: The most prominent effect of BDNF was seen in 0 h group with a marked decreases in brain edema and levels of MDA and a significantly alleviated neuronal apoptosis while it was lowered obviously when administered at 4 h after the insult. CONCLUSION: BDNF exerts a prominent protective effect on hypoxic-ischemic encephalopathy in neonatal rats when given as early as possible after the injury rather than later administration.

Objective:To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor.Methods:Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan- Meier method. Results:A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95% CI 5.4-9.5 months), significantly longer compared with 4.1 months (95% CI 3.1-5.1 months) in the non-radiotherapy group ( P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95% CI 12.3-18.1 months) vs. 9.3 months (95% CI 6.1-12.5 months)]( P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups ( P=0.154). Conclusions:Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.

OBJECTIVERett syndrome (RTT) is a neurodevelopmental disorder which causes severe mental retardation. This study aimed at elucidating clinical features of 66 Chinese RTT cases diagnosed by The Department of Pediatric Neurology, Peking University First Hospital since 1987, and at analysis of the MeCP2 genotype / phenotype correlation.

METHODSSixty-six RTT cases were followed up every one to two years to get the information of their clinical manifestations and the response to the L-carnitine treatment which was administered to the patients at a dose of 80-100 mg/(kg d). MeCP2 mutation analysis by PCR and sequencing were performed on 39 cases.

RESULTSIn this cohort of cases, the onset of the disease occurred between 3 and 38 months of age, 89% of the cases lost their purposeful hand use at 7 months to six years of age, all the cases had stereotype hand movement which presented at 1 to 5 years of age, 85% of the cases lost language ability at 11 months to eight years of age, 21% of the cases lost the ability of walking at ages of 2 years and 9 months to 15 years. The symptoms/signs such as small head circumference, seizures, breathing irregularities, teeth grinding, scoliosis/ kyphosis were presented in many of the cases. The clinical manifestations were improved in 6 cases after L-carnitine treatment. MeCP2 gene mutation was found in 64% of the cases. Two cases with non-sense mutation C502t (amino acid change R168X) died, two cases with missense mutation C397T (amino acid change R133C) and one case with missense mutation A398T (amino acid change R133H) preserved several words.

CONCLUSIONDeceleration of the head growth, loss of acquired purposeful hand use, stereotype hand movement and language deterioration were the main characteristics of RTT. L-carnitine could improve the clinical manifestation of some cases. There are some correlations between MeCP2 genotype and phenotype.

Adolescent ; Carnitine ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone ; genetics ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Female ; Follow-Up Studies ; Genotype ; Hospitals, University ; Humans ; Infant ; Male ; Methyl-CpG-Binding Protein 2 ; Mutation ; Phenotype ; Repressor Proteins ; genetics ; Rett Syndrome ; drug therapy ; genetics ; pathology ; Treatment Outcome

OBJECTIVETo observe the effects of Salvia miltiorrhiza (SM) on levels of neuropeptide Y1-36 and calcitonin gene-related peptide immune reactive substances (ir-NPY, ir-CGRP) in blood plasma and pons-oblongata after hypoxia-ischemic brain injury (HIBI) in neonatal rats.

METHODSSeven-day old rats were randomized into HIBI group (A), HIBI + SM group (B) and sham operation group(C). And each group was subdivided into 4 subgroups according to the different time after operation. 0.5 ml SM was injected intraperitoneally immediately and every 12 hrs afterwards. Changes of ir-NPY and ir-CGRP levels in plasma and pons-oblongata were observed immediately and 12, 24 and 48 hrs after HIBI by radioimmunoassay.

RESULTSPlasma levels of ir-NPY and ir-CGRP in different times after HIBI were all significantly raised but those in pons-oblongata were either raised or lowered to a certain degree. Part of the elevated ir-NPY could be reversed by SM injection.

CONCLUSIONCentral and peripheral neuropeptide Y1-36 and calcitonin gene-related peptide take part in the pathophysiological process of HIBI, SM could partially reverse the abnormal post-HIBI elevation of ir-NPY, which may be one of the pathways of SM in promoting recovery of damaged brain function.

Animals ; Animals, Newborn ; Brain Ischemia ; blood ; Calcitonin Gene-Related Peptide ; blood ; Drugs, Chinese Herbal ; pharmacology ; Female ; Male ; Neuropeptide Y ; blood ; Peptide Fragments ; blood ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; Salvia miltiorrhiza ; chemistry

BACKGROUNDZengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer. However, the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug. The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP, a Chinese herbal drug, on 7, 12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.

METHODSDMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6 - 8 weeks old) three times per week for six weeks in order to induce the development of oral tumors. Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.

RESULTSTopical application of DMBA to the left pouch of hamsters induced oral tumor formation. Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights. Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P < 0.01) and 22.9% (P < 0.01) respectively. Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK. In addition, ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.

CONCLUSIONThe n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene ; toxicity ; Animals ; Antineoplastic Agents ; therapeutic use ; Cell Transformation, Neoplastic ; drug effects ; Cricetinae ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Mesocricetus ; Mouth Neoplasms ; chemically induced ; drug therapy ; prevention & control