Lesch-Nyhan syndrome(LNS) is a congenital X-linked recessive inherited disorder caused by mutations in the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene.A deficiency of the HPRT enzyme is responsible for the disease.The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis and neurological developmental disorders.Studies have reported there are more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low.Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth.DNA of patient and his family members were extracted from peripheral blood lymphocytes.The coding region and the intron-exon boundaries of HPRT gene were sequenced by standard methods.We found a mutation in exon 3 of the HPRT gene of the patient and his mother (Exon3:c.143G>A), which resulted in an arginine to histidine (p.R48H) substitution in the encoded protein.No activity of the enzyme HPRT was detected in the erythrocytes.The same mutation was reported in several European families, but was found in Chinese family for the first time.Clinicians in China have poor experience in diagnosing LNS case, due to the low incidence in China.Therefore LNS screening for infants or adolescents with hyperuricemia, gouty arthritis and neurological dysfunction should be performed.

Multi-drug resistance is a major clinical challenge today. The good antibacterial effect of gold nanoparticles (AuNPs) based on their unique physical and chemical properties make such systems ideal for application as antibacterial drug carriers or self-modified therapeutic agents both in vitro and in vivo. AuNPs also have good clinical application prospects for their broad antibacterial spectrum, various antibacterial mechanisms and good biocompatibility. However, their structural stability in vivo, antibacterial mechanism, long-term safety and cytotoxicity of the surface modification have yet to be further explored and improved through subsequent studies.

In the present study, changes of the neuronal activity of 5-hydroxytrypamine (5-HT) neurons of dorsal raphe nucleus(DRN) in a rat model of Parkinson's disease (PD) were investigated with glass microelectrode recording. The results showed that the discharge rates of 5-HT neurons in control and PD rats were (1.61+/-0.56) Hz and (2.61+/-1.97) Hz, respectively. The discharge rate of PD rats was significantly increased when compared to that of the control rats. In control rats, 79% of 5-HT neurons discharged regularly and 21% in bursts. In PD rats, however, 36% of 5-HT neurons discharged regularly, 16% irregularly and 47% in bursts. The percentage of 5-HT neurons discharging in bursts was obviously higher than that of the control rats (P<0.05). The data suggest that the discharge rate and bursting pattern of 5-HT neurons in DRN are increased in a rat model of Parkinson's disease.
Animals ; Electrophysiology ; Male ; Microelectrodes ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Raphe Nuclei ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

In vivo extracellular recordings were made in the subthalamic nucleus (STN) of intact control rats and rats with 5,7-dihydroxytryptamine (5,7-DHT) -produced lesion of dorsal raphe nucleus (DRN). The results showed that the firing rate of STN neurons in control rats and DRN-lesioned rats were (6.93+/-6.55) Hz and (11.27+/-9.31) Hz, respectively, and the firing rate of DRN-lesioned rats significantly increased when compared to the control rats (P<0.01). In control rats, 13% of STN neurons discharged regularly, 46% irregularly and 41% in bursts. In DRN-lesioned rats, 9% of STN neurons discharged regularly, 14% irregularly and 77% in bursts, the percentage of STN neurons firing in bursts was obviously higher than that of the control rats (P<0.01). In addition, the mean interspike interval coefficient of variation of STN neurons in control rats and DRN-lesioned rats were (0.05+/-0.04) and (0.11+/-0.09), respectively. The mean interspike interval coefficient of variation of DRN-lesioned rats was significantly higher than that of the control rats (P<0.001). These results show that the firing rate and the bursting pattern rate of neurons in STN of DRN-lesioned rats increase significantly, suggesting that DRN inhibits the neuronal activity of the subthalamic neurons in the intact rat.
5,7-Dihydroxytryptamine ; pharmacology ; Adrenergic Agents ; pharmacology ; Animals ; Electrophysiological Phenomena ; Male ; Neurons ; physiology ; Random Allocation ; Raphe Nuclei ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; physiopathology

BACKGROUND: High-volume hemofiltration (HVHF) is technically possible in severe acute pancreatitis (SAP) patients complicated with multiple organ dysfunction syndrome (MODS). Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar-arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with refractory septic shock. METHODS: A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups: fluid resuscitation (group A, n=41), and fluid resuscitation plus high-volume hemofiltration (group B, n=48). The levels of O2 content of central venous blood (CcvO2), arterial oxygen content (CaO2), alveolar-arterial oxygen pressure difference P(A-a)DO2, ratio of arterial oxygen pressure/alveolar oxygen pressure (PaO2/PAO2), respiratory index (RI) and oxygenation index (OI) were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times (0, 24, 72 hours and 7 days of treatment) in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups. RESULTS: The levels of CcvO2, CaO2 on day 7 in group A were significantly lower than those in group B (CcvO2: 0.60±0.24 vs. 0.72±0.28, P<0.05; CaO2: 0.84±0.43 vs. 0.94±0.46, P<0.05). The level of oxygen extraction rate (O2ER) in group A on the 7th day was significantly higher than that in group B ( 28.7±2.4 vs. 21.7±3.4, P<0.01). The levels of P(A-a)DO2 and RI in group B on the 7th day were significantly lower than those in group A. The levels of PaO2/PAO2 and OI in group B on 7th day were significantly higher than those in group A (P<0.05 or P<0.01). The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A (8.2±3.8 vs. 17.2±6.8, P<0.01). CONCLUSION: HVHF combined with fluid resuscitation can improve alveolar- arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.

OBJECTIVETo investigate the role of small G-protein RhoA in neointimal formation following rat carotid artery balloon injury and related mechanisms.

METHODSMale 3-4-month-old Sprague-Dawley rats were used in the present study (10 rats per group). Group A: control; Group B: carotid artery balloon injury; Group C: injury + Ad-CMV-eGFP + Pluronic F-127; Group D: injury + Ad-CMV-N19RhoA-eGFP + Pluronic F-127; Group E: non injury + Ad-CMV-eGFP + Pluronic F-127. Perivascular gene transfer of an adenovirus co-expressing N19RhoA was performed to rat carotid artery following balloon injury and the effect on neointimal formation and the expressions of PCNA and α-SM-actin examined. Rats were killed after 14 days.

RESULTSThe protein expression of RhoA in group B was significantly higher than in group A (P = 0.001), and the positive cells rate of PCNA and α-SM-actin which were assessed by immunohistochemistry in group C (45.2% and 75.6%) was significantly higher than in group D (28.4% and 51.9%, all P < 0.01). The area of neointima was significantly smaller [(0.14 ± 0.08) mm(2) vs. (0.23 ± 0.10) mm(2), P < 0.01], the luminal area was significantly larger [(0.47 ± 0.11) mm(2) vs. (0.31 ± 0.06) mm(2), P < 0.01] in group D than in group C.

CONCLUSIONGene transfer of N19RhoA attenuates neointimal formation after balloon injury in rat carotid arteries possibly related to the modulating capacities of small G-protein RhoA on the proliferation, phenotypic differentiation and migration of vascular adventitial fibroblasts.

Adenoviridae ; genetics ; Animals ; Carotid Arteries ; metabolism ; Carotid Artery Injuries ; metabolism ; pathology ; Genetic Vectors ; Male ; Muscle, Smooth, Vascular ; metabolism ; Neointima ; Rats ; Rats, Sprague-Dawley ; Transfection ; rhoA GTP-Binding Protein ; genetics

ObjectiveTo explore the sensory processing characteristics of preschool children with autism spectrum disorder （ASD）， and to provide a theoretical basis for early screening and intervention training of ASD. MethodsA total of 215 preschool children with ASD and170 typically developed （TD） children were investigated with a basic situation questionnaire and sensory processing measure （SPM）. The two groups were stratified according to age and gender， and the differences of scores in sensory domains were compared to analyze the sensory processing characteristics of preschool children with ASD. ResultsThe scores of social participation， vision， hearing， touch， taste and smell， body awareness， balance and motion， planning and ideas， and total sensory system in children with ASD were all higher than those in children with TD （all P<0.01）. The highest degree of abnormality was found in hearing and the lowest degree in taste and smell in children with ASD. The results of Spearman correlation analysis showed that in the 4-year-old and 5-year-old children with ASD， the scores of vision （r_s=-0.200， P= 0.033） and hearing （r_s=-0.194， P=0.040） decreased with age. There was no correlation between the scores of other developmental quotients and age （all P>0.05）. Boys and girls with ASD had higher scores in all developmental quotients than TD children （P<0.01）. However， there was no significant gender difference in any developmental quotients of ASD children （all P>0.05）. ConclusionSensory processing abnormalities are common in preschool children with ASD， which are different from those of TD children in multiple sensory domains. Sensory processing abnormalities may be used as an indicator for early screening of ASD， and it is necessary to conduct corresponding intervention training for sensory processing abnormalities in children with ASD.

OBJECTIVETo assess the possible genotype-phenotype correlation for GJB2.

METHODSRetrospectively analyzed GJB2 gene mutations with non-syndromic hearing impairment (NSHI) patients and their families audiological data. Individuals were grouped, according to non-truncated mutant (non-truncating, NT) and truncating mutations (truncating, T), into T/T group, T/NT group and NT/NT group. And according to whether they carry 235delC, grouped into 235delC/235delC group, 235delC/Non-235del group and Non-235delC/Non-235delC group.

RESULTSGrouped according to whether the truncation mutants:Fisher exact statistical analysis showed that the degree of hearing loss among the three groups did not meet the random distribution (P = 0.003) , T/T group was significantly higher than T/NT group (P = 0.000) and NT/NT group (P = 0.000) on the degree of hearing loss. Grouped according to whether they carry 235delC mutation: degrees of hearing loss among the three groups were statistically significant differences. Respectively pairwise comparisons (Fisher exact test) found 235delC/235delC group was significantly higher than 235delC/Non-235delC on the degree of hearing loss group (P = 0.001) and Non-235delC/Non-235delC group (P = 0.000), 235delC/Non-235delC group higher than Non-235delC/Non-235delC group (P = 0.033). In GJB2 mutations homozygous and compound heterozygous mutation genotype:G109A/G109A, 235delC/512insAACG, 299delAT/G109A and 235delC/G109A degree of hearing loss caused by genotype was significantly lower than 235delC/235delC group.

CONCLUSIONS235delC homozygotes have significantly more hearing impairment, when compared with 235delC/non-235delC compound heterozygotes. People with two non-235delC mutations have even less hearing impairment. Patients with non-truncation mutants (G109A) suffer from lighter hearing loss than truncation mutations(235delC, 299delAT).

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Connexin 26 ; Connexins ; genetics ; Deafness ; genetics ; Genotype ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Mutation ; Pedigree ; Young Adult

BACKGROUNDThe Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer.

METHODSThirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan-Meier were used to analyze the differences between two group or three groups.

RESULTSNRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression.

CONCLUSIONDownregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

Adult ; Aged ; Animals ; Apoptosis ; genetics ; physiology ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; Cell Survival ; genetics ; physiology ; Female ; Humans ; In Vitro Techniques ; Kaplan-Meier Estimate ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Proteins ; genetics ; metabolism ; Proteins ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Thyroid Neoplasms ; genetics ; metabolism ; mortality ; pathology

Illustrated Classic of Materia Medica （Ben Cao Tu Jing）， compiled in 1061， is regarded as the crystallization of the second national survey of Chinese medicinal resources in the history of China after the Newly Revised Materia Medica （Xin Xiu Ben Cao）， which serves as a precious source for exploring the Chinese medicinal resources in the Song Dynasty. The Illustrated Classic of Materia Medica （Ben Cao Tu Jing） covers 50 illustrations for Chinese medicinal materials named after geographical names of Jiangsu Province， 39 of which have been verified in today's Jiangsu Province. To be specific， Chinese medicinal materials in 32 illustrations can be traced back to their species， those in four illustrations to genera， and those in three illustrations to family. The remaining 12 illustrations remain to be further verified. The origins of most Chinese medicinal materials in the illustrations can be traced， which is attributed to their exquisiteness and lifelikeness as well as the detailed descriptions of the characters of the original plants and animals. In the textual research of these illustrations， we have noticed that there are inconsistencies between pictures and texts， and different illustrations may be derived from the same origin. This is believed to be related to SU Song's principle of collation that "for all Chinese medicinal materials presented as examples， if their shapes and categories recorded are not consistent with those in the literature， they will be retained. If there is any connection with the literature， they will be annotated according to literature to make their origins clear". As revealed by the distribution of Chinese medical materials in Jiangsu Province reported in the Illustrated Classic of Materia Medica （Ben Cao Tu Jing）， the utilization and development of Jiangsu medicinal materials during the Northern Song Dynasty were mainly concentrated in the low-altitude valleys and coastal areas. It could be seen from the illustrations of Chinese medicinal materials named after geographical names of today's Jiangsu Province that the production areas with a large number of illustrations were relatively developed in politics， economy， and transportation at that time， which enabled the medicinal resources to be fully utilized.