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Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6–18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3–3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2–2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4–12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95% CI 2.1–2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age ± standard error (SE) was (65.700 ± 0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean ± SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6 ± 16.3), ranging from (13,310.1 ± 12.8) in IS to (81,369.8 ± 260.7) in SAH, and out-of-pocket expenses were (5788.9 ± 8.6), ranging from (4449.0 ± 6.6) in IS to (30,778.2 ± 156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95% CI 9.2–9.2%), ranging from 6.4% (95% CI 6.4–6.5%) for IS to 21.8% for ICH (95% CI 21.8–21.9%). From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT + MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95% CI 3.2–3.3%), 7.7% (95% CI 7.5–8.0%), and 12.9% (95% CI 12.3–13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95% CI 8.8–9.0%), 16.5% (95% CI 16.2–16.9%), and 16.8% (95% CI 16.2–17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [% (95% CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95% CI 14.6–15.0%) and 14.0% (95% CI 13.8–14.2%), respectively. The mortality rate [% (95% CI)] of stroke at 3-month and 12-month was 4.2% (95% CI 4.1–4.3%) and 8.5% (95% CI 8.4–8.6%), respectively. The recurrence rate [% (95% CI)] of stroke at 3-month and 12-month was 3.6% (95% CI 3.5–3.7%) and 5.6% (95% CI 5.4–5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China. [ABSTRACT FROM AUTHOR]

Background: Impaired fasting glucose (IFG) is a prediabetic condition. Considering that the clinical symptoms of IFG are inconspicuous, these tend to be easily ignored by individuals, leading to conversion to diabetes mellitus (DM). In this study, we established a prediction model for the onset risk of IFG in the Chongqing health check-up population to provide a reference for prevention in a health check-up cohort. Methods: We conducted a retrospective longitudinal cohort study in Chongqing, China from January 2009 to December 2019. The qualified subjects were more than 20 years old and had more than two health check-ups. After following the inclusion and exclusion criteria, the cohort population was randomly divided into a training set and a test set at a ratio of 7:3. We first selected the predictor variables through the univariate generalized estimation equation (GEE), and then the training set was used to establish the IFG risk model based on multivariate GEE. Finally, the sensitivity, specificity, and receiver operating characteristic curves were used to verify the performance of the model. Results: A total of 4,926 subjects were included in this study, with an average of 3.87 check-up records, including 2,634 males and 2,292 females. There were 442 IFG cases during the follow-up period, including 286 men and 156 women. The incidence density was 26.88/1000 person-years for men and 18.53/1000 person-years for women (P<0.001). The predictor variables of our prediction model include male (relative risk (RR) =1.422, 95 % confidence interval (CI): 0.923-2.193, P=0.3849), age (RR=1.030, 95 %CI: 1.016-1.044, P<0.0001), waist circumference (RR=1.005, 95 %CI: 0.999-1.012, P=0.0975), systolic blood pressure (RR=1.004, 95 %CI: 0.993-1.016, P=0.4712), diastolic blood pressure (RR=1.023, 95 %CI: 1.005-1.041, P=0.0106), obesity (RR=1.797, 95 %CI: 1.126-2.867, P=0.0140), triglycerides (RR=1.107, 95 %CI: 0.943-1.299, P=0.2127), high-density lipoprotein cholesterol (RR=0.992, 95 %CI: 0.476-2.063, P=0.9818), low-density lipoprotein cholesterol (RR=1.793, 95 %CI: 1.085-2.963, P=0.0228), blood urea (RR=1.142, 95 %CI: 1.022-1.276, P=0.0192), serum uric acid (RR=1.004, 95 %CI: 1.002-1.005, P=0.0003), total cholesterol (RR=0.674, 95 %CI: 0.403-1.128, P=0.1331), and serum creatinine levels (RR=0.960, 95 %CI: 0.945-0.976, P<0.0001). The area under the receiver operating characteristic curve (AUC) in the training set was 0.740 (95 %CI: 0.712-0.768), and the AUC in the test set was 0.751 (95 %CI: 0.714-0.817). Conclusions: The prediction model for the onset risk of IFG had good predictive ability in the health check-up cohort. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular disease (CVD) survivors are at a high risk of recurrent stroke. Although it is thought that survivors with higher risk of stroke respond better to stroke onset, to date, no study has been able to demonstrate that. Thus, we investigated whether the intent to call emergency medical services (EMS) increased with recurrent stroke risk among CVD survivors.Methods: A cross-sectional community-based survey was conducted from January 2017 to May 2017, including 187,723 adults (age ≥ 40 years) across 69 administrative areas in China. A CVD survivor population of 6290 was analyzed. According to the stroke risk score based on Essen Stroke Risk Score, CVD survivors were divided into three subgroups: low (0), middle (1-3) and high (4-7) recurrent risk groups. Multivariable logistic regression models were used to identify the association between the stroke risk and stroke recognition, as well as stroke risk and EMS calling.Results: The estimated stroke recognition rate in CVD survivors with low, middle, and high risk was 89.0% (503/565), 85.2% (3841/4509), and 82.5% (1001/1213), respectively, while the rate of calling EMS was 66.7% (377/565), 64.3% (2897/4509), and 69.3% (840/1213), respectively. The CVD survivors' knowledge of recognizing stroke and intent to call EMS did not improve with recurrent stroke risk, even after adjustment for multiple socio-demographic factors.Conclusions: Despite being at a higher risk of recurrent stroke, Chinese CVD survivors showed poor knowledge of stroke, and their intent to call EMS did not increase with recurrent stroke risk. Enhanced and stroke risk-orientated education on stroke recognition and proper response is needed for all CVD survivors. [ABSTRACT FROM AUTHOR]

Background: Malignant peripheral nerve sheath tumors (MPNSTs) arise from a peripheral nerve or display nerve sheath differentiation. Most MPNSTs typically originate on the trunk, extremities, head, neck, and paravertebral regions. Gastrointestinal MPNSTs are rare entities with only 10 cases reported worldwide in the literatures. Case presentation: Here, we report the first Chinese case of a malignant peripheral nerve sheath tumor of the distal ileum presenting as intussusception. A 53-year-old female patient without pathological antecedent for neurofibromatosis was admitted with pain in the right lower abdomen and multiple episodes of vomiting for 1 week. Preoperative diagnosis was intussusception with a contrast-enhanced computed tomography scan (CECT) of the abdomen showing characteristic target sign. Due to difficulty reducing the ileum-colon intussusception, right hemicolectomy with ileocolostomy was performed. Histopathology was suggestive of low-grade MPNST. The patient received postoperative care and was followed up for 9 months. There is no sign of tumor recurrence and metastatic disease. Conclusions: This case is unique in terms of a rare tumor presenting with unusual complication. [ABSTRACT FROM AUTHOR]

Background: Morvan syndrome is a rare disorder characterized by the combination of peripheral nerve hyperexcitability, encephalopathy and dysautonomia with marked insomnia. It was reported to have association to antibodies to voltage-gated potassium channels including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab). LGI1-Ab was reported to associate with seizures, amnesia, confusion, hyponatraemia and a good prognosis, while CASPR2-Ab with peripheral presentations, probable risk for tumor and a poor prognosis. The vast majority of Morvan syndrome patients were male, with normal magnetic resonance imaging of the brain.Case Presentation: We report a female case presenting with a combination of bilateral leg pain, widespread myokymia, memory disturbance, seizure, hyperhidrosis and insomnia. She had antibodies targeting CASPR2 and LGI1, tested by the indirect immunofluorescence test, which demonstrated the diagnosis of typical Morvan syndrome as well as classical limbic encephalitis. Cranial MRI revealed bilateral hyper-intensity of the medial temporal lobe, insular lobe and basal ganglia on T2/FLAIR and DWI sequence. As the treatment carried on, her serum LGI1-Ab disappeared and her memory loss, seizure and confusion quickly relieved. But her peripheral presentations did not relieve until serum CASPR2-Ab turned negative. Intravenous immunoglobulin treatment showed limited efficacy while she achieved almost complete remission with corticosteroids therapy.Conclusions: This case provides a rare female resource of Morvan syndrome, which is the first patient with both CASPR2-Ab and LGI1-Ab positive Morvan syndrome in China and one of the few female patients with Morvan syndrome reported so far. Through the detailed analysis of her clinical course, the diverse and overlapping clinical phenotype of CASPR2-Ab and LGI1-Ab in patients with Morvan syndrome was obvious and interesting. [ABSTRACT FROM AUTHOR]

Background: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention.Methods and Results: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-κB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not.Conclusions: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects. [ABSTRACT FROM AUTHOR]

Background: As health behavior varies with increasing age, we aimed to examine the potential barriers in calling emergency medical services (EMS) after recognizing a stroke among 40-74- and 75-99-year-old adults.Methods: Data were obtained from a cross-sectional community-based study (FAST-RIGHT) that was conducted from January 2017 to May 2017 and involved adults (age ≥ 40 years) across 69 administrative areas in China. A subgroup of residents (153675) who recognized stroke symptoms was analyzed. Multivariable logistic regression models were performed in the 40-74 and 75-99 age groups, separately, to determine the factors associated with wait-and-see behaviors at the onset of a stroke.Results: In the 40-74 and 75-99 age groups, the rates of participants who chose "Self-observation at home" were 3.0% (3912) and 3.5% (738), respectively; the rates of "Wait for family, then go to hospital" were 31.7% (42071) and 33.1% (6957), respectively. Rural residence, living with one's spouse, low income (< 731 US $ per annum), having a single avenue to learn about stroke, and having friends with stroke were factors associated with waiting for one's family in both groups. However, unlike in the 40-74 age group, sex, number of children, family history, and stroke history did not influence the behaviors at stroke onset in the 75-99 age group.Conclusions: Different barriers from recognizing stroke and calling an ambulance exist in the 40-74 and 75-99 age groups in this specific population. Different strategies that mainly focus on changing the "Wait for family" behavior and emphasize on immediately calling EMS are recommended for both age groups. [ABSTRACT FROM AUTHOR]

Background: Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥ 30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke.Methods/design: We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥ 30°) head position as a 'business as usual' stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period.Discussion: HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke.Trial Registration: ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014. [ABSTRACT FROM AUTHOR]

Background: Celastrol is a promising anti-tumor agent, yet it also elevates heat shock proteins (HSPs), especially HSP70, this effect believed to reduce its anti-tumor effects. Concurrent use of siRNA to increase celastrol's anti-tumor effects through HSP70 interference has been reported, but because siRNA technology is difficult to clinically apply, an alternative way to curb unwanted HSP70 elevation caused by celastrol treatment is worth exploring.Methods: In this work, we explore three alternative strategies to control HSP70 elevation: (1) Searching for cancer cell types that show no HSP70 elevation in the presence of celastrol (thus recommending themselves as suitable targets); (2) Modifying HSP70-inducing chemical groups, i.e.: the carboxyl group in celastrol; and (3) Using signaling molecule inhibitors to specifically block HSP70 elevation while protecting and/or enhancing anti-tumor effects.Results: The first strategy was unsuccessful since celastrol treatment increased HSP70 in all 7 of the cancer cell types tested, this result related to HSF1 activation. The ubiquity of HSF1 expression in different cancer cells might explain why celastrol has no cell-type limitation for HSP70 induction. The second strategy revealed that modification of celastrol's carboxyl group abolished its ability to elevate HSP70, but also abolished celastrol's tumor inhibition effects. In the third strategy, 11 inhibitors for 10 signaling proteins reportedly related to celastrol action were tested, and five of these could reduce celastrol-caused HSP70 elevation. Among these, the peptide deformylase (PDF) inhibitor, actinonin, could synergize celastrol's proliferation inhibition.Conclusions: Concurrent use of the chemical agent actinonin could reduce celastrol's HSP70 elevation and also enhance proliferation inhibition by celastrol. This combination presents a novel alternative to siRNA technology and is worth further investigation for its potentially effective anti-tumor action. [ABSTRACT FROM AUTHOR]

Background: Human cytomegalovirus (HCMV) is an important pathogen of viral pneumonia in children. The diagnosis of acute HCMV infection is complicated and difficult.Methods: Clinical and laboratory data of 6063 hospitalized children with respiratory infection and 509 with respiratory virus infection alone were retrospectively analyzed. Urine and respiratory specimens of 186 hospitalized children with pneumonia were also prospectively collected. Real-time polymerase chain reaction (PCR) and a chemiluminescent assay were used to detect HCMV DNA copy number, the pp65 gene, and HCMV IgM.Results: The patients with respiratory virus infection alone and those with pulmonary HCMV infection (n = 422) were mostly children aged <6 months old (82.91%, 422/509). The accuracy of urine HCMV DNA (82.32%) was higher than that of HCMV IgM (67.78%), indicating that PCR of urine samples is suitable for determining pediatric acute pulmonary HCMV infection. There was no significant difference in detecting HCMV DNA or the pp65 gene between urinary and respiratory specimens (P > 0.05) in 186 pediatric pneumonia cases. The accuracy of the pp65 gene measured in urine for determining acute pulmonary HCMV infection was the highest (93.01%).Conclusions: Our study shows a novel method for investigating acute pulmonary HCMV infection in children by using real-time PCR and non-invasive samples. This study also highlights the superiority and potential use of the pp65 gene as an important target for the diagnosis of acute pulmonary HCMV infection. [ABSTRACT FROM AUTHOR]

Background: Capsular warning syndrome (CWS) is rare (1.5% of TIA presentations) but has a poor prognosis (7-day stroke risk of 60%). Up to date, the exact pathogenic mechanism of CWS has not been fully understood. We report the clinical presentations and high-resolution MRI (HR MRI) findings of two cases with capsular warning symptoms.Case Presentation: Case 1 was a 63-year-old man with a history of hypertension with recurrent episodes of left hemiparesis and dysarthria lasting 10 ~ 30 minutes. Case 2 was a 54-year-old woman with repetitive episodes of transient left hemiparesis and dysarthria lasting about 10 minutes. Capsular infarctions on DWI were demonstrated in the territory of a lenticulostriate artery in both 2 patients. HR MRI disclosed atherosclerotic plaques on the ventral wall of the MCA where enticulostriate arteries were arisen from, although traditional digital subtraction angiography showed normal. Aggressive medical therapy with dual antithrombotic agents and statin was effective in these two cases.Conclusion: Our HR MRI data offer an insight into the pathophysiology of CWS which might be caused by atherosclerotic plaque in non-stenotic MCA wall. HR MRI might be a useful modality for characterizing atherosclerotic plaques in the MCA and detecting the pathophysiology of the CWS. [ABSTRACT FROM AUTHOR]

Background: Previous studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects., Methods: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008., Results: In total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78., Conclusions: Our data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.

Background: Lysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown., Results: In this report, we found that polo-like kinase 1 (PLK1) directly interacted with LSD1 and phosphorylated LSD1 at Ser-126 . Nocodazole-induced metaphase arrest promoted release of LSD1 from chromatin, and the phosphorylation-defective mutant LSD1 (S126A) failed to dissociate from chromatin upon nocodazole treatment., Conclusions: Taken together, our findings demonstrate that phosphorylation of LSD1 at Ser-126 by PLK1 promotes its release from chromatin during mitosis.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) arise from a peripheral nerve or display nerve sheath differentiation. Most MPNSTs typically originate on the trunk, extremities, head, neck, and paravertebral regions. Gastrointestinal MPNSTs are rare entities with only 10 cases reported worldwide in the literatures., Case Presentation: Here, we report the first Chinese case of a malignant peripheral nerve sheath tumor of the distal ileum presenting as intussusception. A 53-year-old female patient without pathological antecedent for neurofibromatosis was admitted with pain in the right lower abdomen and multiple episodes of vomiting for 1 week. Preoperative diagnosis was intussusception with a contrast-enhanced computed tomography scan (CECT) of the abdomen showing characteristic target sign. Due to difficulty reducing the ileum-colon intussusception, right hemicolectomy with ileocolostomy was performed. Histopathology was suggestive of low-grade MPNST. The patient received postoperative care and was followed up for 9 months. There is no sign of tumor recurrence and metastatic disease., Conclusions: This case is unique in terms of a rare tumor presenting with unusual complication.

Background: Previous studies suggested the potential interactions between cerebrovascular diseases and impaired renal function. However, the relationship between renal function and white matter hyperintensity (WMH), marker of cerebral small vessel disease, in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown., Methods: We consecutively enrolled 1632 subjects with AIS or TIA who underwent brain MRI for this analysis. The severity of WMH in both of periventricular (PVH) and deep subcortical white matter (SDWMH) was evaluated using Fazekas scale. Estimated glomerular filtration rate (eGFR) was calculated by the equation of the Modification Diet for Renal Disease. Multinomial logistic regression was performed to evaluate the association between the severity of WMH and eGFR., Results: Advanced age and hypertension were independently associated with the severity of both PVH and SDWMH (all p < 0.001). There is a significantly inverse association between eGFR and PVH. Patients having each 30 ml/min/1.73 m 2 increase in eGFR was associated with 75 % of risk of having degree 3 of WMH in periventricular areas compared with degree 0 (p = 0.04, OR = 0.75, 95 % CI 0.61-0.92). However this inverse association was not found between eGFR and SDWMH (P = 0.50, OR = 0.93, 95 % CI0.75-1.14)., Conclusion: Our study demonstrates that renal dysfunction (eGFR) is independently associated with the severity of PVH but not SDWMH in patients with acute ischemic stroke. This results highlighted different pathological mechanism and risk factors of PVH and SDWMH.

Background: Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation., Methods: The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR., Results: The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA., Conclusion: The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

Background: Morvan syndrome is a rare disorder characterized by the combination of peripheral nerve hyperexcitability, encephalopathy and dysautonomia with marked insomnia. It was reported to have association to antibodies to voltage-gated potassium channels including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab). LGI1-Ab was reported to associate with seizures, amnesia, confusion, hyponatraemia and a good prognosis, while CASPR2-Ab with peripheral presentations, probable risk for tumor and a poor prognosis. The vast majority of Morvan syndrome patients were male, with normal magnetic resonance imaging of the brain., Case Presentation: We report a female case presenting with a combination of bilateral leg pain, widespread myokymia, memory disturbance, seizure, hyperhidrosis and insomnia. She had antibodies targeting CASPR2 and LGI1, tested by the indirect immunofluorescence test, which demonstrated the diagnosis of typical Morvan syndrome as well as classical limbic encephalitis. Cranial MRI revealed bilateral hyper-intensity of the medial temporal lobe, insular lobe and basal ganglia on T2/FLAIR and DWI sequence. As the treatment carried on, her serum LGI1-Ab disappeared and her memory loss, seizure and confusion quickly relieved. But her peripheral presentations did not relieve until serum CASPR2-Ab turned negative. Intravenous immunoglobulin treatment showed limited efficacy while she achieved almost complete remission with corticosteroids therapy., Conclusions: This case provides a rare female resource of Morvan syndrome, which is the first patient with both CASPR2-Ab and LGI1-Ab positive Morvan syndrome in China and one of the few female patients with Morvan syndrome reported so far. Through the detailed analysis of her clinical course, the diverse and overlapping clinical phenotype of CASPR2-Ab and LGI1-Ab in patients with Morvan syndrome was obvious and interesting.

Background: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention., Methods and Results: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-κB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not., Conclusions: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects.

Background: Genome-wide Association Studies (GWAS) are typically designed to identify phenotype-associated single nucleotide polymorphisms (SNPs) individually using univariate analysis methods. Though providing valuable insights into genetic risks of common diseases, the genetic variants identified by GWAS generally account for only a small proportion of the total heritability for complex diseases. To solve this "missing heritability" problem, we implemented a strategy called integrative Bayesian Variable Selection (iBVS), which is based on a hierarchical model that incorporates an informative prior by considering the gene interrelationship as a network. It was applied here to both simulated and real data sets., Results: Simulation studies indicated that the iBVS method was advantageous in its performance with highest AUC in both variable selection and outcome prediction, when compared to Stepwise and LASSO based strategies. In an analysis of a leprosy case-control study, iBVS selected 94 SNPs as predictors, while LASSO selected 100 SNPs. The Stepwise regression yielded a more parsimonious model with only 3 SNPs. The prediction results demonstrated that the iBVS method had comparable performance with that of LASSO, but better than Stepwise strategies., Conclusions: The proposed iBVS strategy is a novel and valid method for Genome-wide Association Studies, with the additional advantage in that it produces more interpretable posterior probabilities for each variable unlike LASSO and other penalized regression methods.

Background: Because some of heat shock protein 90's (HSP90) clients are key cell cycle regulators, HSP90 inhibition can affect the cell cycle. Recently, celastrol is identified both as a novel inhibitor of HSP90 and as a potential anti-tumor agent. However, this agent's effects on the cell cycle are rarely investigated. In this study, we observed the effects of celastrol on the human monocytic leukemia cell line U937 cell cycle., Results: Celastrol affected the proliferation of U937 in a dose-dependent way, arresting the cell cycle at G0/G1 with 400 nM doses and triggering cell death with doses above 1000 nM. Cell cycle arrest was accompanied by inhibition of HSP90 ATPase activity and elevation in HSP70 levels (a biochemical hallmark of HSP90 inhibition), a reduction in Cyclin D1, Cdk4 and Cdk6 levels, and a disruption of the HSP90/Cdc37/Cdk4 complex. The observed effects of celastrol on the U937 cell cycle were thiol-related, firstly because the effects could be countered by pre-loading thiol-containing agents and secondly because celastrol and thiol-containing agents could react with each other to form new compounds., Conclusions: Our results disclose a novel action of celastrol-- causing cell cycle arrest at G0/G1 phase based upon thiol-related HSP90 inhibition. Our work suggests celastrol's potential in tumor and monocyte-related disease management.

Background: Adenoid cystic carcinoma is a high malignant carcinoma characterized by intensive local invasion and high incidence of distant metastasis. Although many reports have demonstrated that angiogenesis has played an important role in tumor metastasis, the relationship between metastasis characters and angiogenesis ability in high and low metastasis cell lines of Adenoid cystic carcinoma has rarely been reported. The present study aimed to compare the angiogenesis ability of ACC-M (high metastasis) and ACC-2 (low metastasis) cell lines in vitro. Furthermore, the activity of nuclear factor kappaappa B and the expression of vascular endothelial growth factor (VEGF) in ACC-2 and ACC-M were also detected., Methods: Electrophoretic mobility shift assay was used to detect nuclear factor kappaappa B activity. Semi-quantitative RT-PCR was used to quantify the mRNA level of VEGF. Immuofluorescence double staining and semi-quantitative confocal laser scanning analysis was carried out to detect nuclear factor kappaappa B nuclear localization and staining intensity of VEGF. The angiogenesis ability of ACC-M and ACC-2 was compared by an in vitro three-dimensional angiogenic model assay. The vector transfection assay was performed to transfect the PCMV-IkappaBalphaM vector into ACCs cell lines expressing the phosphorylation defective IkappaBalphaM., Results: Nuclear factor kappaappa B activity and the rate of nuclear factor kappaappa B nuclear localization in ACC-M was significantly higher than that in ACC-2. Moreover, ACC-M exhibited higher mRNA and protein levels of vascular endothelial growth factor than ACC-2. VEGF mRNA expression was effectively decreased by inhibition of nuclear factor kappaappa B activity. Furthermore, ACC-M could remarkably stimulate the migration and tube formation of endothelial cells and induce The umbilical vein endothelial cells sprouting into the gel matrix., Conclusion: These results implicated that ACCs cells with higher metastasis feature might present greater angiogenesis ability.