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 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

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

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.

In clinical practice,methotrexate exhibits individual difference in drug efficacy and adverse reactions.Genetic variation is one of the most important influence factors.The article reviewed latest researches of methotrexate in metabolism,transport,and targets to discover the relationship between gene polymorphisms on pharmacogenomics and methotrexate so as to provide references for clinical individualized treatment.

Objective To investigate the role of small G-protein RhoA in neointimal formation following rat carotid artery balloon injury and related mechanisms.Methods Male 3-4-month-old SpragueDawley 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.Results The 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) mm2 vs.(0.23 ± 0.10) mm2,P ＜ 0.01 ],the luminal area was significantly larger [ (0.47 ± 0.11 ) mm2 vs.(0.31 ±0.06) mm2,P ＜ 0.01 ] in group D than in group C.Conclusion Gene 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.

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.

Background::Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods::We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results::A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. Conclusions::Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

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