Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

A Novel Cold-Adapted and High-Alkaline Alginate Lyase with Potential for Alginate Oligosaccharides Preparation.

Alginate oligosaccharides (AOs) prepared through enzymatic reaction by diverse alginate lyases under relatively controllable and moderate conditions possess versatile biological activities. But widely used commercial alginate lyases are still rather rare due to their poor properties (e.g., lower activity, worse thermostability, ion tolerance, etc.). In this work, the alginate lyase Alyw208, derived from Vibrio sp. W2, was expressed in Yarrowia lipolytica of food grade and characterized in order to obtain an enzyme with excellent properties adapted to industrial requirements. Alyw208 classified into the polysaccharide lyase (PL) 7 family showed maximum activity at 35 °C and pH 10.0, indicating its cold-adapted and high-alkaline properties. Furthermore, Alyw208 preserved over 70% of the relative activity within the range of 10-55 °C, with a broader temperature range for the activity compared to other alginate-degrading enzymes with cold adaptation. Recombinant Alyw208 was significantly activated with 1.5 M NaCl to around 2.1 times relative activity. In addition, the endolytic Alyw208 was polyG-preferred, but identified as a bifunctional alginate lyase that could degrade both polyM and polyG effectively, releasing AOs with degrees of polymerization (DPs) of 2-6 and alginate monomers as the final products (that is, DPs 1-6). Alyw208 has been suggested with favorable properties to be a potent candidate for biotechnological and industrial applications.

[Clinical study of a adjustable movable retractor for maxillary labially inverted impacted central incisor].

PURPOSE: To evaluate the orthodontic treatment outcome of a new adjustable movable retractor for patients with maxillary labially inverted impacted central incisors. METHODS: Ten patients, aged 7 to 10 years, who had a maxillary labially inverted impacted central incisor, were treated using a new adjustable movable retractor. Cone-beam CT(CBCT) was taken before treatment and after treatment immediately. Pulp electrical activity test and periodontal probing were performed after treatment. The parameters of the treated incisors and contralateral ones served as controls were compared.SPSS 23.0 software package was used for data analysis. RESULTS： The success rate of treatment in 10 patients was 100%. The mean duration of treatment was（8.60±1.26） months. There were no loosening, gingival swelling and redness, periodontal pockets, and pulp necrosis in the treatment group. However, the labial gingival height of the treatment group was (10.58±0.45) mm, significantly higher than that of the control group [(9.47±0.31) mm]. The growth and development level of the treatment group was higher than that of the control group during traction. The root length[(2.80±1.09) mm] and apical foramen [(1.79±0.59) mm] of the treatment group were higher than those of the control group[(1.84±0.97) mm and (0.96±0.40) mm]. Before treatment, the root growth of the treatment group was retarded. The root length of the treatment group[(7.28±1.03) mm] was shorter than that of the control group[(9.80±1.46) mm]; meanwhile, the apical foramen width of the treatment group[(2.18±0.63) mm] was larger than that of the control group[(1.26±0.40) mm]. After treatment, the root length [(10.08±0.63) mm] of the treatment group was still shorter than that of the control group [(11.75±0.90) mm]. The labial alveolar bone level of the treatment group [(1.77±0.37) mm] was higher than that of control group[(1.25±0.26) mm]. The palatal alveolar bone level of treatment group[(1.23±0.21) mm] was also slight higher than that of the control group[(1.05±0.15) mm]. The thickness of the alveolar bone in the treatment group[(1.49±0.31) mm] was thinner than that in the control group[(1.80±0.11) mm]. CONCLUSIONS： The effect of the new adjustable movable retractor for maxillary labially inverted impacted central incisor is reliable. Traction therapy can promote root development, and the periodontal and endodontic condition is well after treatment.

Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys.

Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASD), in the hippocampus (DG and CA1-4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs (sgRNAs) targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions, and defective social reward behaviors. Furthermore, some aspects of ASD and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.

Effect of inappropriate admissions on hospitalization performance in county hospitals: a cross-sectional study in rural China.

BACKGROUND: Inappropriate admissions cause excessive utilization of health services compared with outpatient services. However, it is still unclear whether inappropriate admissions cause excessive use of health services compared with appropriate admissions. This study aims to clarify the differences in the hospitalization performances between appropriately admitted inpatients and inappropriately admitted inpatients. METHODS: A total of 2575 medical records were obtained after cluster sampling in three counties. Admission appropriateness was assessed by appropriateness evaluation protocol (AEP). The propensity score matching (PSM) was computed to match patients in treatment and control group with similar characteristics, and to examine the differences in the utilization of hospitalization services between the two groups. The samples were matched in two major steps in this study. In the first step, total samples were matched to examine the differences in the utilization of hospital services between the two groups using 15 individual covariates. In the second step, PSM was computed to analyze the differences between the two groups in different disease systems using 14 individual covariates. RESULTS: For the whole sample, the inappropriate group has lower expenditure of hospitalization (EOH) (difference = - 0.12, p = 0.003) and shorter length of stay (LOS) (difference = - 0.73, p = 0.016) than the appropriate group. For number of clinical inspection (NCI), it has no statistically significant difference (difference = - 0.39, p = 0.082) between the two groups. Among different disease systems, no significant differences were observed between the two groups among EOH, LOS and NCI, except that the EOH was lower in the inappropriate group than that in the appropriate group for surgical disease (difference = - 0.169, p = 0.043). CONCLUSION: Inappropriate admissions have generated excessive health service utilization compared with appropriate admissions, especially for internal diseases. The departments in charge of medical services and hospital managers should pay high attention to the health service utilization of the inappropriately admitted inpatients. Relevant medical policies should be designed or optimized to increase the appropriateness in health care service delivery and precision in clinical pathway management.

Effect of integrated urban and rural residents medical insurance on the utilisation of medical services by residents in China: a propensity score matching with difference-in-differences regression approach.

OBJECTIVES: In this study, we aim to evaluate the effect of urban and rural resident medical insurance scheme (URRMI) on the utilisation of medical services by urban and rural residents in the four pilot provinces. SETTING AND PARTICIPANTS: The sample used in this study is 13 305 individuals, including 2620 in the treatment group and 10 685 in the control group, from the 2011 and 2015 surveys of China Health and Retirement Longitudinal Study. OUTCOME MEASURES: Propensity score matching and difference-in-differences regression approach (PSM-DID) is used in the study. First, we match the baseline data by using kernel matching. Then, the average treatment effect of the four outcome variables are analysed by using the DID model. Finally, the robustness of the PSM-DID estimation is tested by simple model and radius matching. RESULTS: Kernel matching have improved the overall balance after matching. The URRMI policy has significantly reduced the need-but-not outpatient care and significantly increased outpatient care cost and inpatient care cost for rural residents, with DID value of -0.271, 0.090 and 0.256, respectively. After robustness test, the DID competing results of four outcome variables are consistent. CONCLUSIONS: URRMI has a limited effect on the utilisation of medical and health services by all residents, but the effect on rural residents is obvious. The government should establish a unified or income-matching payment standard to prevent, control the use of medical insurance funds and increase its efforts to implement URRMI integration in more regions to improve overall fundraising levels.

siRNA­mediated knockdown of T­bet and RORγt contributes to decreased inflammation in pre­eclampsia.

Abnormal immune response resulting from disordered T helper (Th)1/Th2 and Th17/regulatory T cells (Treg) cytokine expression has been demonstrated to serve an important role in the pathogenesis of preeclampsia (PE). However, the role of transcription factors regulating Th cell differentiation contributing to PE remain unclear. To determine whether a decrease in the expression of the T cell lineage transcription factor T­bet can restore immune balance and alleviate the systemic inflammatory response present in PE, 30 patients diagnosed with PE were assessed and compared with healthy pregnant controls. The expression of the transcription factors T­bet and retinoic acid receptor­related orphan receptor (ROR)γt were increased in the peripheral blood mononuclear cells of PE patients compared with controls, consistent with the presence of abnormally high T­bet:GATA3 and RORγt:forkhead box (FOX) P3 ratios. The present study additionally identified a high­efficiency, specific small interfering (si)RNA that can downregulate RORγt and T­bet mRNA levels and inhibit protein expression. This effective siRNA was transfected into activated CD4+ T cells derived from patients with PE to observe the changes to transcription factor expression and attempt to elucidate the regulatory mechanism of T cell subsets. It was identified that knockdown of RORγt induced increased expression of FOXP3 and that the ratios of RORγt:FOXP3 and interleukin (IL)­17A:IL­10 were subsequently decreased. The results suggested that siRNA­mediated knockdown of T­bet regulated the immune balance of Th17/Tregs via changes to RORγt and FOXP3. When siRNA against RORγt and T­bet were used in combination, a stronger ability to regulate immune balance was observed. These results imply that Th1­ and Th17­type immunity is dominant in PE and that the siRNA­mediated knockdown of certain Th1 and Th17 cell transcription factors may be an effective therapeutic target for promoting immune balance in CD4+ T cell subgroups and ameliorating local and generalized inflammation in PE.

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

Vascular endothelial growth factor affects dendritic cell activity in hypertensive disorders of pregnancy.

Vascular endothelial growth factor (VEGF) activity is involved in the growth and stability of the placenta, and its signaling has been implicated in the development of pregnancy­induced hypertension (PIH). The present study sought to evaluate VEGF levels and dendritic cell (DC) profiles in patients with PIH, and to investigate the effects of VEGF expression on DC phenotypes. The present study assessed 162 patients, 112 of whom were diagnosed with PIH. Serum VEGF was measured by ELISA, while myeloid DC (mDC; (Lin1­HLA­DR+CD11c+) and plasmacytoid DC (pDC; Lin1­HLA­DR+CD123+) counts were determined using flow cytometry. In order to determine the effect of VEGF treatment on DC phenotypes, immature DCs (iDCs) were separated from monocytes by culturing in the presence of cytokines (GM­CSF, IL­4), and then pretreated with VEGF or lipopolysaccharide (LPS). The phenotype of dendritic cells (CD14, CD80, CD83, or CD86) was determined by flow cytometry. The levels of VEGF in the serum of patients with PIH were significantly lower than those in control subjects (P<0.05). The percentage of pDCs found in the serum of patients with preeclampsia was significantly lower than that in the other groups. The percentage of mDCs in the serum of patients with preeclampsia and eclampsia was significantly higher than that in the control and hypertensive disorder groups (P<0.05). The percentage of mDCs was significantly negatively correlated with the levels of VEGF in the preeclamptic and eclamptic patients (r=­0.34 and r=­0.42, respectively; P<0.05). Detected levels of CD80, CD83 and CD86 in DCs treated with VEGF were significant lower than those in DCs treated with LPS alone (P<0.05). In conclusion, abnormal expression of VEGF and an altered dendritic cell profile may be involved in the development of PIH.

[Calculating method for crop water requirement based on air temperature].

The importance of accurately estimating crop water requirement for irrigation forecast and agricultural water management has been widely recognized. Although it has been broadly adopted to determine crop evapotranspiration (ETc) via meteorological data and crop coefficient, most of the data in whether forecast are qualitative rather than quantitative except air temperature. Therefore, in this study, how to estimate ETc precisely only using air temperature data in forecast was explored, the accuracy of estimation based on different time scales was also investigated, which was believed to be beneficial to local irrigation forecast as well as optimal management of water and soil resources. Three parameters of Hargreaves equation and two parameters of McClound equation were corrected by using meteorological data of Xinxiang from 1970 to 2010, and Hargreaves equation was selected to calculate reference evapotranspiration (ET0) during the growth period of winter wheat. A model of calculating crop water requirement was developed to predict ETc at time scales of 1, 3, and 7 d intervals through combining Hargreaves equation and crop coefficient model based on air temperature. Results showed that the correlation coefficients between measured and predicted values of ETc reached 0.883 (1 d), 0.933 (3 d), and 0.959 (7 d), respectively. The consistency indexes were 0.94, 0.95 and 0.97, respectively, which showed that forecast error decreased with the increasing time scales. Forecasted accuracy with an error less than 1 mm x d(-1) was more than 80%, and that less than 2 mm x d(-1) was greater than 90%. This study provided sound basis for irrigation forecast and agricultural management in irrigated areas since the forecasted accuracy at each time scale was relatively high.

[Temporal and spatial variation of water requirement of winter wheat and its influencing factors in Henan Province, China].

Based on mean meteorological data of ten days in 17 observation stations from 1961 to 2012, the reference crop evapotranspiration was computed using Penman-Monteith formula recommended by FAO. The water requirement of winter wheat in Henan Province was calculated by adopting crop coefficients and the growth stage of winter wheat from the "National Irrigation Experiment Database", and the temporal and spatial distribution, variation and affecting factors in recent 51 years were analyzed by means of time-series analysis and gray relational grade analysis. The results showed that the average water requirement of winter wheat was 345-492 mm in Henan Province from 1961 to 2011, and it was lowest at Lushi station and highest at Mengjin station. The average water requirement of winter wheat was lowest from 1980 to 1989 and highest from 1961 to 1969 at most stations. The water requirement of winter wheat showed a tendency to increase with years at the 7 stations (Xinxiang, Luanchuan, Kaifeng, Xixia, Nanyang, Xinyang and Gushi) , while it indicated a tendency to decline in the other 10 stations. The water requirement of winter wheat in North Henan was higher than in South Henan, and had a high span variation in West Henan. During the growing period of winter wheat, the average daily maximum and minimum temperatures showed a tendency to increase with years, while the average daily wind speed and relative humidity, and the sunshine hours had a tendency to decline. In Henan Province, the water requirement of winter wheat was mainly affected by the average daily maximum temperature and the sunshine hours, and least influenced by the average daily relative humidity.

Generation of a monkey with MECP2 mutations by TALEN-based gene targeting.

Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey (Macaca fascicularis) carrying MECP2 mutations using transcription activator-like effector nucleases (TALENs)-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frameshifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey's brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. RESULTS: Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. CONCLUSIONS: Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.

Dendritic cells derived from preeclampsia patients influence Th1/Th17 cell differentiation in vitro.

Immune regulation plays important but as-yet-unclear roles in the development of preeclampsia. This study explored potential contributions to immune regulation by dendritic cells (DCs) derived from peripheral blood of preeclampsia patients on the differentiation of Th1 and Th17 cells. Pregnant women with preeclampsia (n = 73) and healthy pregnant women (n = 80) were included in the study. Peripheral blood samples were collected from each participant, and DCs were derived from peripheral blood mononuclear cells in vitro. The phenotypes of DCs, identified by CD14, CD80, CD83, and CD86 expression, were detected by flow cytometry, and secretion of interleukin-23 (IL-23) into the culture medium by DCs was measured by ELISA. CD4 + T cells were separated by the magnetic beads and subjected to flow cytometry to determine their ability to differentiate to Th1 or Th17 cells. Compared with DCs derived from healthy pregnant women, DCs derived from preeclampsia patients expressed higher levels of CD83, CD80, and CD86 (P < 0.05). Additionally, secretion of IL-23 was higher in DCs derived from the preeclampsia group than from the control group (P < 0.001). DCs derived from preeclampsia patients also had a stronger ability to promote the differentiation of CD4 + T cells into Th1/Th17 cells when cultured with different cytokines (P < 0.01). Thus, altered phenotypes and functions of DCs may promote the abnormal balance of Th1 and Th17 in the development of preeclampsia.

[Characteristics of soil microbial community under different vegetation types in Wuyishan National Nature Reserve, East China].

By using Biolog Ecoplate system, this paper studied the structure and functional diversity of soil microbial community under different vegetation types in Wuyishan National Nature Reserve, aimed to probe into the effects of vegetation type on the diversity of soil microbial community. The results showed that the soil chemical properties, soil enzyme activities, and average well color development (AWCD) were higher in natural forest than in planted forest, and were the lowest in abandoned field. The AWCD reflecting soil microbial activity and functional diversity was increased with increasing incubation time, but there existed significant differences among different vegetation types. The carbon sources mostly used by soil microbes were carbohydrates and carboxylic acids, followed by amino acids, phenolic acids and polymers, and amines had the lowest utilization rate. The Simpson index, Shannon index, Richness index and McIntosh index in natural forest were holistically higher than those in planted forest. Principal component analysis (PCA) identified 2 principal component factors in relation to carbon sources, explaining 56.3% and 30.2% of the variation, respectively. The carbon sources used by soil microbial community differed with vegetation types. Amino acids and amides were the two main carbon sources separating the 2 principal component factors. The results of this study could provide basis for further approaching the relationships between vegetation diversity and soil microbial community diversity.

[Clinical significance of miR-143 expression in women with cervical cancer of Uyghur and Han ethnicities, in Xinjiang].

OBJECTIVE: To explore the expression of microRNA(miR)-143 and related association to clinicopathologic features of cervical cancer in both Uygur and Han women with cervical cancer in Xinjiang. METHODS: The expression levels of miR-143 in the specimens from 34 non-tumor and 66 cervical cancer tissues, were examined by quantitative real-time PCR. Levels on the expression of miR-143 in Xinjiang Uygur women and the correlations between the expression levels of miR-143 and related clinicopathologic features of cervical cancer were analyzed. RESULTS: The expression levels of miR-143 were significantly lower in the tumor tissues than that in the non-tumor tissues (P < 0.05) but no significant difference was found between women with Uygur or Han ethnicities. Down-regulated miR-143 expression was associated with both the tumor size and lymph node metastasis in patients with cervical cancer(Z = -2.628, P = 0.009 and Z = -2.127, P = 0.033 respectively). No significant associations were found between the expression levels of miR-143 and factors as age, depth of tumor invasion, parametrial infiltration, clinical stage, types of histology and stage of differentiation. ROC curve analysis on miR-143 expression in cervical cancer patients with different tumor sizes and lymph node metastasis:the rates on AUC were 0.711 and 0.697, both larger than 0.5, respectively. The sensitivity and specificity of evaluating tumor size were 85.7% and 62.2%. The sensitivity and specificity of lymph node metastasis were 72.2% and 60.4% . CONCLUSION: It seemed that miR-143 play an important role in the processes of generation and progression of cervical cancer. However, there was no significant difference found between the different ethnic groups. The expression level of miR-143 might serve as a valuable adjuvant parameter for diagnosing and predicting the state of cervical cancer.

[Tissue engineered bone scaffold material in restoration of alveolar socket after extraction of lower impacted third molar].

PURPOSE: To investigate the effects of tissue engineered bone scaffold material in the restoration of alveolar socket after extraction of lower impacted third molar. METHODS: Thirteen patients were immediately implanted with Bio-oss or PerioGlas® in the alveolar cavity after impacted mandibular third molar extraction. Clinical observation and X-ray were taken 1 to 12 weeks after operation. Paired t test was used for statistical analysis by SPSS10.0 software package. RESULTS: Thirteen patients did not experience postoperative complications. The distal alveolar height of the second molar and the gingival attachment did decrease significantly 1 to 12 weeks after operation(P < 0.05). CONCLUSION: Tissue engineered bone scaffold material is helpful in the restoration of alveolar socket after impacted third molar extraction.

Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice.

BACKGROUND: Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H(2)S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H(2)S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet. METHODS: C57BL/6 mice and homozygous apoE(-/-) mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE(-/-) mice were treated with the same dose of normal saline as the apoE(-/-) group, injected intraperitoneally with sodium hydrosulfide (NaHS, an H(2)S donor, 56 µmol/kg per day) as the apoE(-/-) + NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-γ-lyase inhibitor, 50 mg/kg, per day) as the apoE(-/-) + PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit. RESULTS: Compared with control mice, apoE(-/-) mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE(-/-) mice, H(2)S donor-treated apoE(-/-) mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H(2)S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE(-/-) mice, PPG treated apoE(-/-) mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE(-/-) + PPG rats did not significantly differ from those in the apoE-/-mice. Consistently, H(2)S induced SOD expression, accompanied by a reduced level of ROS. CONCLUSION: H(2)S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE(-/-) mice fed with a Western type diet.

[Differential expressed genes in eutopic endometrium of endometriosis patients: comparison between Uygur and Han women in Xianjiang].

OBJECTIVE: To investigate the reason why the incidence of endometriosis (EM) is lower in the Uygur women than in the Han women. METHODS: Eutopic and ectopic endometrium samples were obtained by operation and biopsy from 26 EM patients, 10 Uygur women and 16 Han women and analyzed with a gene expression microarray containing the cDNAs of 22 000 human genes. Twenty-two women, 10 Uygur and 12 Han, were used as controls. RESULTS: Eleven differentially expressed genes, 7 up-regulated and 6 down-regulated, were screened out from the eutopic endometrium of the Uygur women with EM. 58 differential expressed genes were screened out from the in eutopic endometrium of the Han women with EM, 53 being up-regulated and 5 down-regulated. Five genes were screened out in both groups, 3 being up-regulated and 2 down-regulated. CONCLUSION: The number of differentially expressed genes of the Uygur women with EM is lower than that of the Han women with EM, which may be the cause of relative low incidence of EM among Uygur women.