"Microtia, Branchial Cleft Fistula, and Tetralogy of Fallot: A Possible Association".

When searching over associations between congenital ear abnormalities, especially microtia and affiliated deformities like cleft lip or palate and congenital heart diseases, some clinical analysis and genetic theories are found. A 10-year-old boy sent to the plastic surgery hospital was puzzled by a congenital anterior auricular fistula with fluid trace for more than 9 years. The preoperative diagnoses were branchial cleft fistula and congenital left ear deformity with postoperation of TOF. By browsing over studies on genetic concerns and clinical performance, it may be attributed to a possible association between microtia, branchial cleft fistula, and tetralogy of Fallot, though whose fundamental mechanisms remain concerned.

Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer.

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.

Diagnostic value of BinaxNOW antigen card for Severe Acute Respiratory Syndrome Coronavirus 2.

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing.

The interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ. The labelled adenines and the endogenous methylated CpG sites are simultaneously detected on individual nanopore reads using a hidden Markov model, which is implemented in the nanoHiMe software package. We demonstrate the utility, robustness and sensitivity of nanoHiMe-seq by jointly profiling DNA methylation and histone modifications at low coverage depths, concurrently determining phased patterns of DNA methylation and histone modifications, and probing the intrinsic connectivity between these epigenetic marks across the genome.

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

Rare leptin in non-alcoholic fatty liver cirrhosis: A case report.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)-related cirrhosis is mainly caused by NAFLD by causing inflammation which leads to fibrosis. The role of leptin in NAFLD-related cirrhosis has been rarely reported. CASE SUMMARY: This study presents the case of a 65-year-old male patient who was referred to The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China, for diagnosis and treatment for liver cirrhosis. Initially, the cause of liver cirrhosis was unknown. After radiology, laboratory examination, pathological results and analysis of the patient's signs and symptoms, the case was finally diagnosed with final NAFLD-related cirrhosis. Although this study reports a single case, the findings might expand the understanding of leptin's role in NAFLD-related cirrhosis and might provide a basis for the clinical diagnostic criteria, pathological features and treatment of NAFLD-related cirrhosis. CONCLUSION: Although the occurrence of marasmus NAFLD-related cirrhosis is rare, it needs to be distinguished from other liver diseases, including viral hepatitis, drug-induced liver disease, Wilson's disease and autoimmune liver disease. Aggressive treatment is needed to prevent the progression of NAFLD-related cirrhosis.

Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro.

The developmental potential of oocytes decreases with time after ovulation in vivo or in vitro. Epitalon is a synthetic short peptide made of four amino acids (alanine, glutamic acid, aspartic acid, and glycine), based on a natural peptide called epithalamion extracted from the pineal gland. It is a potent antioxidant, comparable to melatonin, that may confer longevity benefits. The current study aims to test the protective effects of Epitalon on the quality of post-ovulatory aging oocytes. Epitalon at 0.1mM was added to the culture medium, and the quality of oocytes was evaluated at 6h, 12h, and 24h of culture. We found that 0.1mM Epitalon reduced intracellular reactive oxygen species. Epitalon treatment significantly decreased frequency of spindle defects and abnormal distribution of cortical granules during aging for 12h and 24h, while increased mitochondrial membrane potential and DNA copy number of mitochondria, thus decreasing apoptosis of oocytes by 24h of in vitro aging. Our results suggest that Epitalon can delay the aging process of oocytes in vitro via modulating mitochondrial activity and ROS levels.

[Corrigendum] Transforming growth factor­ß1 induces fibrosis in rat meningeal mesothelial cells via the p38 signaling pathway.

Subsequently to the publication of this paper, while performing a careful re­examination of the scientific integrity of the data included in their publications, the authors have realized that they inadvertently used the incorrect western blotting images in Fig. 2B of this article, However, still having access to their original data, the authors were able to reassemble Fig. 2 correctly, and the corrected version of this figure is shown below. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors thank the Editor of Molecular Medicine Reports for granting them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published on Molecular Medicine Reports 14: 1709­1713, 2016; DOI: 10.3892/mmr.2016.5411].

The relationship between anti epidemic mentality and post traumatic stress disorder in medical college students during the COVID-19 pandemic / 中国学校卫生

Objective@#To explore the relationship between an anti epidemic mentality and post traumatic stress disorder (PTSD) among college students during the corona virus disease 2019 (COVID-19) pandemic, and to provide a scientific basis for the prevention of PTSD when college students experience sudden crisis events in the future.@*Methods@#An online questionnaire survey was conducted among 9 399 undergraduates from Shanxi Medical University using the Posttraumatic Stress Disorder Checklist Civilian Version (PCL-C) and the public anti epidemic psychology self examination scale.@*Results@#During the COVID-19 pandemic, the total PCL-C scores of college students were (22.74±7.78), and the positive rate of PTSD symptoms was 5.3%. The detection rates of symptom recurrence, avoidance/numbness symptoms and increased alertness symptoms were 27.0%, 16.6% and 8.6 %, respectively. The average score of avoidance/numbness symptoms in the three symptom groups was (9.21±3.39), the two items with the highest scores were repeated recall of traumatic events (1.57±0.71) and impaired concentration (1.47±0.71). Females scored higher than males on the increased alertness dimension(6.82±2.61，6.67±2.72) ( t = -6.49 ， P <0.05). In respect to PCL-C total scores and the scores of each dimension, rural areas were associated with higher scores than urban areas, and non medical students scored higher than medical students, while the scores of those who grew up with siblings were higher than only children ( P <0.05). There was a significant positive correlation between an anti epidemic mentality and total PTSD scores ( r =0.51, P <0.01). Multiple regression analysis showed that the place of origin, choice of college major, and antiepidemic mentality were predictors of PTSD symptoms ( P <0.01).@*Conclusion@#Anti epidemic mentality is associated with the occurrence of PTSD among college students.

Improved A40926 production from Nonomuraea gerenzanensis using the promoter engineering and the co-expression of crucial genes.

The semi-synthetic antibiotic dalbavancin is clinically used in the treatment of severe infections caused by multidrug resistant Gram-positive pathogens. So far, fermentation has still been the only approach for the production of A40926 in the industrial scale, which is used as the precursor of dalbavancin and biosynthesized by the rare actinomycete Nonomuraea gerenzanensis (N. gerenzanensis). Therefore, it is particularly essential and necessary to enhance the yield of A40926 continually. In this paper, we firstly assessed the activity of 6 heterologous promoters using the enhanced green fluorescence protein (EGFP) reporter system in N. gerenzanensis. Furthermore, the strongest constitutive promoter gapdh confirmed in this study was applied to separately overexpress the total of ten dbv genes involved in the A40926 biosynthesis. PCR and RT-qPCR were successively carried out to verify the mutant and the overexpression of dbv genes. As a consequence, the overexpression of dbv3 and dbv20 genes both increased the A40926 production remarkably. Based on the above consequences, a mutant strain named N320 laboring the co-expression of dbv3 and dbv20 was constructed. The results of fermentation showed that the N320 strain enhanced the yield of A40926 from 163 mg/L to 272 mg/L.

Highly efficient genome editing in N. gerenzanensis using an inducible CRISPR/Cas9-RecA system.

OBJECTIVE: To develop an inducible CRISPR/Cas9-Recombinase A (RecA) system to manipulate genes in Nonomuraea gerenzanensis effectively. RESULTS: Compared with traditional homologous recombination, the inducible CRISPR/Cas9 system achieved 68.8% editing efficiency, whereas, with both the inducible Cas9 and the overexpressed RecA, the efficiency of the combined genome editing system reached 100%. The dbv23-deleted mutant obtained by the inducible CRISPR/Cas9-RecA system was confirmed to produce more A40926 with an approximate yield of 200 mg L-1 than that of around 150 mg L-1 produced by the wild-type strain. CONCLUSIONS: This inducible CRISPR/Cas9-RecA system was successfully constructed and can be utilized as an efficient genome editing tool for Actinomyces able to shorten editing time simultaneously.

Preparation of pH-Responsive Alginate-Chitosan Microspheres for L-Valine Loading and Their Effects on the A40926 Production.

The glycopeptide A40926 biosynthesized by Nonomuraea gerenzanensis is a precursor of the second generation glycopeptide antibiotic dalbavancin. The skeleton of this glycopeptide consists of seven amino acids and is biosynthesized by the NRPS gene module. L-valine, a branched amino acid, is also a significant precursor for A40926 production. This study details the use of pH-responsive alginate-chitosan microspheres loaded with L-valine prepared by internal emulsification gelation. The effects of process and formulation variables on microsphere size, loading capacity, and encapsulation efficiency were investigated. Then, effects on A40926 production by the pH-responsive microspheres were evaluated in a 10-L fermenter. Results demonstrated that use of the pH-responsive microspheres could improve A40926 yield from 465 to 602 mg L-1 in a 10-L scale fermenter.

Comparing public and private emergency departments in China: Early evidence from a national healthcare quality survey.

The number of private healthcare facilities has rapidly increased since the progressive open market policies, which began in the 1980s; however, little is known about the development of private emergency departments (EDs). This cross-sectional study was part of the National Control Information System (NCIS) project, which collects data annually from hospitals across China. Emergency services data were extracted and included location, infrastructure, human resources, beds, and number of patients; 4529 hospitals across 31 provinces in mainland China were eventually included, consisting of 988 private and 3541 public EDs. Evidence shows that most private EDs are located in central China, where local economies are relatively developed. Most private EDs (91.6%) are found in secondary hospitals but have significantly fewer beds and smaller workforces compared with public EDs. An imbalance of emergency medical resources was observed across China, and this disparity becomes even more profound in rural hospitals. These findings may initiate collaborative, public-private partnerships in emergency health services provision and suggest there is a need to offer tax breaks to incentivize investors, but further research is required. We may also need to rethink health insurance policies, which could enable more equitable access to private emergency care. Future planning and health policies must be based upon the strongest available evidence, if we are to address imbalanced health services distribution and growing demand.

Overview of Research on Chinese Medicine Patents for Prevention and Treatment of Asthenopia and Analysis Their Medication Rule / 中国实验方剂学杂志

Objective: To explore drug utilizing regularity of traditional Chinese medicine(TCM) in treating and preventing asthenopia by analyzing the patent status of TCM in the field of asthenopia control for nearly 20 years. Method: Global patents about TCM in treating and preventing asthenopia were systematic searched in IncoPat platform.The application trend,legal status and categories of patents were analyzed.Meanwhile,the oral prescriptions and external prescriptions were performed correlation index analysis by IBM SPSS Modeler 18.0,respectively;the difference of compatibility rules between them was compared. Result: The number of global patents in treating and preventing asthenopia gradually increased,and the proportion of patents from China was more than 99%.The main patent applications were pharmaceutical composition,oral preparation,external eye patch and so on,but the ratio of licensed patents in total patents was low.In term of drug utilizing regularity,the oral prescriptions paid much attention to using TCM for nourishing the liver and kidney,while external prescriptions highlighted relieving sickness heat and detoxification. Conclusion: Patents of TCM in treating and preventing asthenopia has been kept increasing in recent years,but the authorization rate is low.Formulation based on TCM theory can be statistically summarized,which can be helpful for the development of anti-asthenopia products.

Activation of ß-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that ß-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of ß-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of ß-adrenoceptor) and isoproterenol (an agonist of ß-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of ß-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of ß-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

Microplastics releasing from personal care and cosmetic products in China.

Microplastics (MPs) have become a major global issue; their release from various products affects the aquatic environment, especially marine ecosystems. As a primary source of MPs, personal care and cosmetics products (PCCPs) containing MPs contribute to this environmental risk. We visited several supermarket chains in Beijing, China to identify PCCPs containing MPs. Overall, 7.1% of facial cleansers contained MPs, with an average weight of 25.04±10.69mgMP/g and average size of 313±130µm; whereas, 2.2% of shower gel products contained an average weight of 17.80±7.50mgMPs/g with an average size of 422±185µm. The majority of MPs were made of polyethylene, based on Raman and Fourier transform-infrared spectra analyses, while only a few were made of walnut shells and carbon particles. Finally, estimated 39tons MPs were released into the environment based on PCCPs use in China based on available data.

Effects of NF-κB inhibitor on nerve injury in rats after intracerebral hemorrhage / 中国病理生理杂志

AIM:To investigate the regulatory effect of nuclear factor-κB (NF-κB) inhibitor, pyrrolidine di-thiocarbamate (PDTC), on nerve function and neural cell apoptosis in rats after intracerebral hemorrhage (ICH).METH-ODS:SPF Sprague-Dawley rats were randomly divided into 4 groups with 6 rats in each group: sham group, ICH group, PDTC at low concentration (Plow) group and PDTC at high concentration (Phigh) group.Autologous blood injection was used to establish ICH model.After 2 h of surgery, the rats in Plow group and Phigh group were intraperitoneal injected with PDTC at 100 mg/kg and 200 mg/kg, respectively , while rats in sham group and ICH group were injected with the same volume of saline .The neurological function score was classified with modified Longa grading method .TUNEL assay was used to detected the neural cell apoptosis , and the content of malondialdehyde ( MDA) and the activity of superoxide dis-mutase (SOD) were measured.Furthermore, the protein levels of p-P65 and cleaved caspase-3 in brain tissues were deter-mined by Western blot .RESULTS: Compared with sham group , the rats in ICH group had higher neurological function score (P<0.05).After treatment with PDTC, the neurological function score was decreased (P<0.05), but no signifi-cant difference between P low group and P high group was observed .Compared with sham group , the number of apoptotic cells in ICH group was increased ( P<0.05 ) .After treatment with PDTC , the neural cell apoptosis was restrained , and the number of apoptotic cells in Phigh group was lower than that in Plow group (P<0.05).Compared with sham group, the con-tent of MDA was increased and the activity of SOD was decreased in ICH group (P<0.05).After treatment with PDTC, the content of MDA was decreased while the activity of SOD was increased , and the variation trend was more obvious in Phigh group (P<0.05).Compared with sham group, the protein levels of p-P65 and cleaved caspase-3 in ICH group were increased (P<0.05).After treatment with PDTC, the protein levels of p-P65 and cleaved caspase-3 were decreased, and those in Phigh group were lower than those in P low group.CONCLUSION: NF-κB inhibitor PDTC plays a role in the se-condary brain injury after ICH , and the protective effect increases at the higher dose .The mechanism may be related to re-ducing MDA content and increasing SOD activity , and further inhibiting neural cell apoptosis .

Overweight and Obesity in Young Adulthood and the Risk of Stroke: a Meta-analysis.

BACKGROUND: A systematic review assessing the association between overweight and obesity in young adulthood and stroke risk is lacking. Therefore, we conducted a meta-analysis to evaluate the association between overweight and obesity in young adulthood and stroke risk. METHODS: We systematically searched PubMed and Embase databases for related studies of human subjects in the English language. Two investigators independently selected original studies in a 2-step process. Fixed- and random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Subgroup analyses were also performed. RESULTS: Eight studies met the inclusion criteria. The pooled adjusted RR of stroke was 1.36 (95% CI: 1.28-1.44) for overweight in young adulthood and 1.81 (95% CI: 1.45-2.25) for obesity in young adulthood. In subgroup analyses, overweight and obesity in young adulthood increased the risk of stroke in most groups, except for the group of stroke subtype. For ischemic stroke, the adjusted RR was 1.40 (95% CI: 1.24-1.58) for overweight in young adulthood and 1.78 (95% CI: 1.003-3.16) for obesity in young adulthood, whereas adjusted RR for hemorrhagic stroke was 1.25 (95% CI: .83-1.90) for overweight in young adulthood and 1.80 (95% CI: .97-3.35) for obesity in young adulthood. CONCLUSIONS: Overweight and obesity in young adulthood are associated with an increased risk of stroke, probably, independent of other cardiovascular risk factors. The risk effect gradually increases with increasing body weight.

Transforming growth factor-ß1 induces fibrosis in rat meningeal mesothelial cells via the p38 signaling pathway.

Leptomeningeal fibrosis is important in the pathogenesis of communicating hydrocephalus following subarachnoid hemorrhage; however, the underlying mechanisms of leptomeningeal fibrosis remain largely unclear. In the present study, primary meningeal mesothelial cells (MMCs) were used as a cell model to investigate the effect of transforming growth factor­ß1 (TGF­ß1) on leptomeningeal fibrosis. Firstly, primary MMCs were isolated from rat brains and characterized by immunofluorescene, staining positive for keratin and vimentin, but negative for factor VIII. Upon TGF­ß1 treatment, MMCs were induced to express connective tissue growth factor (CTGF), an indicator of fibrosis, in a dose­dependent manner. Furthermore, p38 mitogen­activated protein kinase (MAPK) signaling was significantly activated by TGF­ß1. However, in the presence of a p38 MAPK inhibitor, TGF­ß1­induced CTGF expression was markedly suppressed. Together, these data suggest that TGF­ß1 could induce fibrosis of MMCs via the p38 MAPK signaling pathway, providing a novel potential target for intervention in TGF­ß1­induced leptomeningeal fibrosis.