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Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

Objective. Chronic low back pain is an overwhelming problem for a wide range of people and leads to tactile acuity deficits. We aimed to investigate the correlations among age, pain severity, disability, and tactile acuity in patients with chronic low back pain by using multiple tactile acuity tests. Methods. A total of 58 participants (36.40 ± 14.95 years) with chronic low back pain were recruited, and two-point discrimination, point-to-point test, and two-point estimation were performed on their painful low back areas. The correlations between age, pain intensity, disability, and tactile acuity were characterized with Pearson’s correlation coefficients. Subgroup analyses according to the median values of age, pain intensity, and disability were used to compare the intergroup difference in tactile acuity. Results. Results illustrated significant negative associations among age, pain intensity, disability, and tactile acuity. Subgroup analyses revealed that patients with below-the-median values of age, pain intensity, and disability had better performance in tactile acuity tests than those with above-the-median values. Conclusion. This study indicated that tactile acuity was negatively associated with age, pain intensity, and disability in young patients with chronic low back pain.

Objectives The purpose of this study was to estimate the fatigue life of premolars restored with two dental ceramics, lithium disilicate (LD) and polymer infiltrated ceramic (PIC) using the numerical method and compare it with the published in vitro data. Methods A premolar restored with full-coverage crown was digitized. The volumetric shape of tooth tissues and crowns were created in Mimics®. They were transferred to IA-FEMesh for mesh generation and the model was analyzed with Abaqus. By combining the stress distribution results with fatigue stress–life (S–N) approach, the lifetime of restored premolars was predicted. Results The predicted lifetime was 1,231,318 cycles for LD with fatigue load of 1400 N, while the one for PIC was 475,063 cycles with the load of 870 N. The peak value of maximum principal stress occurred at the contact area (LD: 172 MPa and PIC: 96 MPa) and central fossa (LD: 100 MPa and PIC: 64 MPa) for both ceramics which were the most seen failure areas in the experiment. In the adhesive layer, the maximum shear stress was observed at the shoulder area (LD: 53.6 MPa and PIC: 29 MPa). Significance The fatigue life and failure modes of all-ceramic crown determined by the numerical method seem to correlate well with the previous experimental study.

Objective Numerous bond strength tests have been performed on dental adhesion experiments. Yet, the validity of these bond strength tests is controversial due to the name ( e.g. , “shear” or “tensile”) may not reflect to the true and complete stress situation, i.e. , assumed uniform shear or uniaxial tensile conditions. Thus, the aim of this study was to simulate and compare the stress distribution of and between shear bond strength (SBS), tensile bond strength (TBS), mold-enclosed shear bond strength (ME-SBS) and de novo lever-induced mold-enclosed shear bond strength (LIME-SBS) tests. Methods 3-Dimensional finite element method (FEM) was used on the dental resin-bonded surfaces ( i.e. , titanium alloy, dentine and porcelain) interphased with adhesive layer (thickness 5 μm) to simulate the mechanical tests. For ME-SBS, both polycarbonate and stainless steel molds were used. For LIME-SBS, stainless steel levers and molds with lengths of 3 mm, 6 mm, 12 mm, 15 mm and 18 mm were used. The applied loads on these models were 50 N, 100 N and 200 N. Results De novo LIME-SBS test was the most optimal configuration to evaluate “shear” bond strength of adhesive in regards to providing significantly high and uniform shear stress as well as eliminating tensile stress at the interface. The conventional SBS test created very high tensile stress at the load area, whereas the TBS created optimal tensile stress but shear stress indeed co-exist. The ME-SBS test could also eliminate some of the tensile stress. Similar stress distributions pattern appeared on the Ti-adhesive models, the dentine-adhesive models and porcelain-adhesive models. Significance None of the bond strength tests could give purely “shear” or “tensile” bond strength, but LIME-SBS seems to be the best model to evaluate the bond strength under true “shear” mode.

Objectives: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. Methods: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. Results: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. Conclusion: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old. Keywords: Epidemic, Hand, foot and mouth disease, Coxsackie virus A16, Human enterovirus 71

OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up. CONCLUSIONS This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

Summary Background Human cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised individuals. The unique long b’ (ULB’) region of HCMV contains at least 19 open reading frames (ORFs); however, little is known about the function of UL145 and UL136. We characterized UL145 and UL136 in low-passage clinical isolates from Chinese infants. Material/Methods The clinical strains of HCMV were recovered from the urine from HCMV-infected infants. Human embryonic lung fibroblasts (HELFs) were infected with clinical isolates of HCMV, and the viral DNA and mRNA for UL145 and UL136 were analyzed by polymerase chain reaction (PCR) and sequencing techniques. We also predicted the structure and function of UL145 and UL136 proteins. Results Sixty-two Chinese infants infected with HCMV were recruited into this study and the clinical isolates were recovered from the urine. Two strains among the low-passage isolates, D2 and D3, were obtained. The UL145 and UL136 sequences were deposited with GenBank under accession numbers of DQ180367, DQ180381, DQ180377, and DQ180389. The mRNA expression of both UL145 and UL136 was confirmed by reverse transcription (RT-PCR) assays. UL145 was predicted to contain 1 protein kinase C phosphorylation site, 2 casein kinase II phosphorylation sites and a zinc finger structure. UL136 was predicted to contain a protein kinase C phosphorylation site, N-myristoylation site, cAMP- and cGMP-dependent protein kinase phosphorylation site and tyrosine kinase II phosphorylation site. Both UL145 and UL136 are highly conserved. Conclusions UL145 may act as an intranuclear regulating factor by direct binding to DNA, while UL136 may be a membrane receptor involving signal transduction.

Purpose: To isolate and characterize primary fetus retinal microvascular endothelial cells (RMECs) in order to facilitate the study of their properties in vitro. Methods: Human RMECs were isolated from abortive fetuses whose gestational ages were between 20 and 28 weeks by mechanical morcel and trypsin-collagenase digestion, plated on fibronectin-coated wells and purified gradually in high-selective condition. The RMECs were characterized for expression and localization of endothelial cell markers by indirect immunocytochemical staining of von Willebrand factor (vWF) and CD34, the distribution of cell markers was observed by confocal immunofluorescence microscope. The ability of these cells to form capillary-like networks was assessed subsequently. Cobalt dichloride (CoCl2) was used to simulate hypoxia in the culture condition and Western blot was used to detect the alternation of VEGF protein level under normoxia and hypoxia. Results: Isolation of fetus RMECs has been very difficult and primary culture of these special premature RMECs has not been previously reported due to many reasons. Here we established a simple and convenient method for the primary culture of fetus human RMECs. Our results show that delicate RMECs could be obtained readily and grow very fast, and the purity of RMECs was up to 95% demonstrated by specific staining for vWF in the cytoplasm. Our research also indicates that nearly 100% of cells could express CD34. The cells were successfully passaged and maintained in culture for 5–7 passages without a significant loss in expression of endothelia cell markers. The fetus RMECs formed capillary-like networks on the Matrigel well. Expression of VEGF protein increased significantly under hypoxia. Conclusions: Pure fetus RMECs could be obtained rapidly and easily by our method.Fetus RMECs have some specific properties. Hypoxia could induce expression of VEGF. Cell properties related with age of the donors should be considered while studying in vitro, especially in some age-specific diseases such as retinopathy of prematurity and diabetic retinopathy.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Intraoperative magnetic resonance imaging (iMRI) dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI (1.0T). This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital, Shanghai, China.From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency.All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas (n = 161) was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients (12.42%) suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients (3.16%). Twenty-one of 161 patients (13.04%) had early speech deficit and late speech deficit was only observed in six of 158 patients (3.80%). The ratio of gross total resection for pituitary adenomas (n = 49) was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy.The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.

Evidence suggests that smoking adversely affects bones. Glutathione S-transferases (GSTs) are important in the detoxification of tobacco smoke compounds. This study investigated the influence of GSTM1 and GSTT1 genetic polymorphisms on the effects on bone induced by tobacco smoking in young men. In total, 231 Chinese men aged 20-39 years were assessed by a cross-sectional study. Calcaneal quantitative ultrasound (QUS) was measured. Smoking information was obtained using a questionnaire. Genotypes were determined for null alleles of GSTM1 and GSTT1. Smoking was inversely associated with speed of sound (SOS) and bone quality index (BQI) among subjects with GSTM1 null genotype (β = -0.28, 95% CI, -34.01 to -8.65 and β = -0.30, 95% CI, -16.41 to -4.49, respectively), but not among those with the allele present (β = -0.02, 95% CI, -15.01 to 12.59 and β = -0.09, 95% CI, -8.75 to 3.02, respectively). P for interaction = 0.04 for SOS and 0.08 for BQI. No interaction was found between the GSTT1 polymorphism and smoking. The results showed that GSTM1 deficiency may increase the adverse effect of smoking on calcaneal QUS in young men, suggesting an interaction between metabolic genes and tobacco smoke in bone detoxification.

Background The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorders. However, such efforts have covered only chromosomal aneuploidy, and fetal methylated DNA biomarkers in maternal whole blood for detecting single-gene diseases remain to be discovered. Methods To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues and compared them with maternal peripheral blood potential in an attempt to detect fetal genes in maternal peripheral blood. First, the methylated-CpG island recovery assay combined with a CpG island array was performed for four fetus-toward placental tissues and the corresponding maternal peripheral bloods. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the methylation status of the hypermethylated genes that were identified by the microarray analysis. Results Three hundred and ten significantly hypermethylated genes in the placental tissues were detected by microarray. From the top 15 hypermethylated genes detected by microarray, two were selected for sequencing validation in placental tissue and chorionic villus samples and four were selected for COBRA validation in four placental tissues, ten amniotic fluids and five chorionic villus samples. The six selected genes were confirmed to be hypermethylated in placental tissue and chorionic villus samples, but methylation of the genes could not be detected in the amniotic fluids. Conclusions Of the many hypermethylated genes and methylation sites that were found in the fetal tissues, some have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical studies are warranted to confirm these findings.

To evaluate preliminary clinical experience for combining awake craniotomy and intraoperative language brain mapping within the integrated 3.0 T intraoperative magnetic resonance imaging (iMRI) suite.From December 2010 to April 2011, 11 right hand-dominant patients with left glioma were involved in, or adjacent to, eloquent cortex was carried out awake craniotomies with cortical stimulation within an integrated 3.0 T iMRI suite. Aphasia battery of Chinese was used to test the language function before the operation. During the procedure, after the occipital, temporal, and supraorbital nerves were blocked by the anesthesiologists, the head was fixed with a custom high-field MRI-compatible head holder. The skull and dura was opened as usual and language brain mapping was then performed. Language testing followed a set protocol: counting numbers from 1 to 50, naming objects, reading single words. Resection of the tumor was guided by neuronavigation system and continued until eloquent areas were encountered or the margin of assessment was reached. An interdissection MRI was acquired to evaluate the glioma removal in a movable MRI scanner after minimal draping. Meanwhile, adverse effects caused by electrical stimulation and iMRI were recorded. The follow-up speech tests were assessed on 7th day and 1 month at least after the operation.The combined use of 3.0 T iMRI and awake craniotomy was performed safely in all patients. No adverse effects were reported. The duration of surgery was prolonged by 2 to 4 h. The patients' perception of iMRI during surgery was favorable. First-look MRI studies led to further resection attempts in 6/11 cases as well as a 3/11 increase in the number of gross-total resections. One week after surgery, baseline language function worsened in 4 cases. However, no patients had a persistent language deficit one month after surgery.Awake craniotomy and direct cortical electrical stimulation can be performed safely and effectively within a 3.0 T iMRI suite. The combination of high-field iMRI and awake craniotomy may facilitate safe removal of eloquent glioma.

To report the preliminary experience in clinical application of 3.0 T intraoperative magnetic resonance imaging (iMRI) neuronavigation system in China.From September 2010 to March 2011, a consecutive series of 122 patients with intracranial lesions underwent operations in guidance with 3.0 T iMRI. A retrospective analysis was conducted regarding clinical efficiency.Among 122 procedures, the numbers of intraoperative scanning were 2 - 4 times with an average of 2.6. The qualities of images were excellent. Due to the discovery and further possibility of resection of residual tumors, the ratio of gross total resection was increased from 71.7% to 90.0% in cerebral gliomas (n = 60), while from 75.9% to 93.1% in macroadenomas (n = 29). There were 6.7% of all patients occurred postoperative paralysis, but only 3.3% of patients had persistent paralysis at 1 - 2 months follow-up. There was no iMRI-related adverse event occurred. During the same period, more than 2500 patients underwent diagnostic MRI scanning.3.0 T iMRI neuronavigation system provides high-quality intraoperative structural, functional and metabolic images for real time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery. The system is cost-effective.

The treatment of gliomas is highly individualized. Surgery for gliomas is essentially for histological diagnosis, to alleviate mass effect, and most importantly, to favor longer survival expectancy. During the past two decades, many surgical techniques and adjuvants have been applied to glioma surgery in China, which lead to a rapid development in the field of cerebral glioma surgery. This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China. A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China. The following databases were searched: the Pubmed (January 1995 to date); China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date). A selection criterion was established to exclude duplicates and irrelevant studies. The outcome measures were extracted from included studies. A total of 3307 articles were initially searched. After excluded by abstracts and full texts, 69 studies conducted in the mainland of China were included and went through further analysis. The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change. Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients. The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention. The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

To analyze the tendency of hospital based surveillance incidence rates of birth defects in Guangdong province to provide reference evidence for related intervention program.Data from hospital based birth defects surveillance of Guangdong province during 1997 - 2007 were analyzed retrospectively.The overall surveillance rates of birth defects in Guangdong province showed an increasing trend form 98.9 per 10 000 birth in 1997 to 244.2 per 10 000 birth in 2007. Among the frequently seen birth defects, the rate of congenital heart diseases increased sharply, but the rates of congenital talipes equinovarus, polydactyly, cleft lip with/without cleft palate showed a slight increasing trend. It seemed that there was a significant difference between different maternal age interval and gender of the infants. Mother's illness, drug use, and exposure to environment harmful factors in early pregnancy stage, high maternal age, negative bearing history were the suspect risk factors for birth defects.The increasing trend of surveillance rate of birth defects seemed to be comprehensively affected by the factors as: method being adopted, target and extension of birth defects surveillance, technology used for diagnosis, kinds of risk factor, and quality control on surveillance programs.

To understand the health status and healthcare service demand of perimenopausal women in Guangdong Province so as to explore the mode and methods for implementing climacteric and senectitude healthcare.Using the method of stratified and cluster sampling and according to the geographical features of Guangdong Province, we selected 4 500 perimenopausal women aged 40-65 years from 5 relatively small cities (representatives of the urban areas) and 4 counties (representatives of the rural areas) for this survey.The average age of natural menopause was 48.6 years in this cohort of women, and was 48.9 years in women from the urban areas and 48.3 years in those from the rural areas. The total incidence of diseases was similar in the urban and rural areas (38.5% vs 39.5%), accounting for an incidence of 39% in the total subjects. The 6 most prevalent diseases were bone and joint disease (12.5%), hypertension (9.2%), myoma of the uterus (6.8%), gastric or duodenal ulcer (5.2%), cardiac disease (2.7%) and diabetes mellitus (2.2%). In bone and joint disease, knee joint disease and lumbar vertebrae disease were the commonest (34.3% vs 32.8%), and the incidence of bone fracture was 2.5%. Perimenopausal syndrome had a prevalence rate of 68.1%, and the most distressful symptoms were sleeplessness, muscular, bone and joint pain, fidgety, dizziness, of which 86.8% were mental symptoms and 86.0% body symptoms. Women(71.2%) with perimenopausal symptoms received no medical treatment, and only 20.5% had ever sought medical care in the department of obstetrics and gynecology, often taking traditional Chinese medicines (53.9%). Only 1.4% of the symptomatic women received hormone therapy, the rate varied from 1.0% in the rural areas to 1.8% in the urban areas.Perimenopausal syndrome and its related diseases severely affect the physical and mental health of perimenopausal women, who demand extensive healthcare services.