Water-Ice Microstructures and Hydration States of Acridinium Iodide Studied by Phosphorescence Spectroscopy.

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5 M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

Rapid room-temperature phosphorescence chiral recognition of natural amino acids.

Chiral recognition of amino acids is very important in both chemical and life sciences. Although chiral recognition with luminescence has many advantages such as being inexpensive, it is usually slow and lacks generality as the recognition module relies on structural complementarity. Here, we show that one single molecular-solid sensor, L-phenylalanine derived benzamide, can manifest the structural difference between the natural, left-handed amino acid and its right-handed counterpart via the difference of room-temperature phosphorescence (RTP) irrespective of the specific chemical structure. To realize rapid and reliable sensing, the doped samples are obtained as nanocrystals from evaporation of the tetrahydrofuran solutions, which allows for efficient triplet-triplet energy transfer to the chiral analytes generated in situ from chiral amino acids. The results show that L-analytes induce strong RTP, whereas the unnatural D-analytes produce barely any afterglow. The method expands the scope of luminescence chiral sensing by lessening the requirement for specific molecular structures.

Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study.

AIMS: Frequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV. METHODS: We conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models. RESULTS: A total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77-0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69-0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01-1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02-1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55-0.75; IRR: 0.86, 95% CI: 0.79-0.93) and glinide (HR: 0.47, 95% CI: 0.31-0.73; IRR: 0.84, 95% CI: 0.73-0.97) may lead to an increased frequency of within-day GV. CONCLUSIONS: An increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

[Evaluation of Efficacy and Prognosis Analysis of Stage III-IV SMARCA4-deficient 
Non-small Cell Lung Cancer Treated by PD-1 Immune Checkpoint Inhibitors plus 
Chemotherapy and Chemotherapy].

BACKGROUND: The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC. METHODS: 46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC. RESULTS: Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC. CONCLUSIONS: Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.

Pleural cryptococcosis diagnosed by pleural biopsy in an immunocompromised patient: a case report.

Objective: The aim of this study is to report an isolated pleural cryptococcosis with pleural effusion as the only manifestation, confirmed by pleural biopsy in a patient with thymoma combined with myasthenia gravis, who developed pleural effusion of unknown origin after long-term glucocorticoids and tacrolimus therapy. Methods: Pathological examination of the right pleural biopsy tissue from a patient with unexplained recurrent pleural effusion was implemented. Morphological analysis of the fungal component and metagenomic next-generation sequencing (mNGS) on the pleural tissue were performed. Results: A biopsy specimen of the right pleura revealed numerous yeast-like organisms surrounded by mucous capsules and Cryptococcus neoformans was detected by mNGS with a species-specific read number (SSRN) of 4, confirming the diagnosis of pleural cryptococcosis. Pleural effusion was eliminated with amphotericin B and fluconazole, and healthy status was maintained at the time of review 1 year later. Conclusion: Cryptococcosis, manifested by simple pleural effusion, is extremely rare, but when repeated pleural effusion occurs in immunocompromised patients or in patients with malignant tumors, the possibility of cryptococcosis should be treated with high vigilance and pleural biopsy is recommended if necessary in order to confirm the diagnosis.

Transcriptomic profiling and longitudinal study reveal the relationship of anti-MDA5 titer and type I IFN signature in MDA5+ dermatomyositis.

Objective: This study aimed to investigate the relationship between anti-MDA5 titer and type I IFN signature in patients with MDA5+ DM. Methods: We explored the transcriptome profiling of PBMCs in MDA5+ DM patients with high-titer of antibody at disease onset or relapse and normal low-titer after treatment and healthy donors. Subsequently, we revealed the dynamic relationship between serum type I IFN scores and antibody titers. Result: Differentially expressed genes in MDA5+ DM patients were enriched for related pathways and biological functions linked to viruses and cytokines compared to healthy donors. Similar differences remained pooled between the high-titer and low-titer group, and type I-specific interferon response genes showed upregulation in high-titer group. Significant correlations were found between anti-MDA5 titers and type I IFN scores (r = 0.50, P< 0.001). Contemporaneous anti-MDA5 titers revealed to be significantly higher in the group with ultra-high type I IFN scores (vs. high group, P = 0.027; vs. low group, P< 0.001). Longitudinal assessment of type I IFN scores and anti-MDA5 titers, including pre- and post-treatment changes at initial diagnosis and dynamic changes during treatment, presented an asynchrony between the two parameters in response to treatment. Conclusion: Anti-MDA5 antibody titers correlated with type I IFN signature in patients with MDA5+ DM and they both changed dynamically but not synchronously over the course of treatment.

Diagnostic efficacy of metagenomic next generation sequencing in bronchoalveolar lavage fluid for proven invasive pulmonary aspergillosis.

Objective: To assess the diagnostic efficacy of metagenomic next generation sequencing (mNGS) for proven invasive pulmonary aspergillosis (IPA). Methods: A total of 190 patients including 53 patients who had been diagnosed with proven IPA were retrospectively analyzed. Using the pathological results of tissue biopsy specimens as gold standard, we ploted the receiver operating characteristic (ROC) curve to determine the optimal cut-off value of mNGS species-specific read number (SSRN) of Aspergillus in bronchoalveolar lavage fluid (BALF)for IPA. Furthermore, we evaluated optimal cut-off value of mNGS SSRN in different populations. Results: The optimal cut-off value of Aspergillus mNGS SSRN in BALF for IPA diagnosis was 2.5 for the whole suspected IPA population, and 1 and 4.5 for immunocompromised and diabetic patients, respectively. The accuracy of mNGS was 80.5%, 73.7% and 85.3% for the whole population, immunocompromised and diabetic patients, respectively. Conclusions: The mNGS in BALF has a high diagnostic efficacy for proven IPA, superioring to Aspergillus culture in sputum and BALF and GM test in blood and BALF. However, the cut-off value of SSRN should be adjusted when in different population.

Long non-coding RNA DSCAS regulates cisplatin sensitivity in lung squamous cell carcinoma by competitively binding to miR-646-3p.

Background: Platinum-based chemotherapy is the main treatment for advanced lung squamous cell carcinoma (LUSC). Eventually, patients with LUSC develop resistance to cisplatin, which affects the prognosis. Hence, the researchers sought to find a lncRNA in LUSC that affects resistance to cisplatin. Methods: The lncRNA microarray assay was used to screen the differential expression of lncRNA. qPCR was used to detect lncRNA DSCAS (DSCAS) expression in tissues and cell lines. Lentiviral transfection was used to regulate the expression of DSCAS. CCK-8, colony formation, wound healing, transwell, and flow cytometry assays were used to assess the biological behaviors and sensitivity to cisplatin of LUSC cell. RNA-RNA interaction was tested using the dual luciferase reporting assay, RNA-IP, and RNA-RNA pull-down assay. The downstream pathway of DSCAS was verified by qPCR and Western blotting assays. Results: DSCAS was highly expressed in LUSC tissues and cells, and its expression levels were higher in cisplatin-insensitive tissues than in cisplatin-sensitive tissues. Elevation of DSCAS promoted cell proliferation, migration and invasion as well as increased cisplatin resistance of lung cancer cells, while demotion of DSCAS inhibited cell proliferation, migration and invasion as well as decreased the cisplatin resistance of lung cancer cells. DSCAS bound to miR-646-3p to regulate the expression of Bcl-2 and Survivin, which affected the cell apoptosis and sensitivity to cisplatin in LUSC cells. Conclusions: DSCAS regulates biological behavior and cisplatin sensitivity in LUSC cells by competitively binding to miR-646-3p to mediate the expression of Survivin and Bcl-2, known as apoptosis-related proteins.

Immunomodulatory effect of polysaccharides isolated from Lonicera japonica Thunb. in cyclophosphamide-treated BALB/c mice.

Lonicera japonica (L. japonica) is utilized as foods and healthy drink around the world. Until now, the immunomodulatory activity of polysaccharides from L. japonica (LJP) is little studied. In our previous work, LJP was fractionated to a neutral component (LJP-N) and an acidic component (LJP-A) by a DEAE-Cellulose column, and LJP-N was a starch-like polysaccharide and LJP-A was a pectic polysaccharide. In this study, LJP-N and LJP-A were investigated for their immunomodulatory effect, and the protective effect of these two polysaccharide fractions against immune injury by cyclophosphamide (CTX) in BALB/c mice was evaluated. Results showed that when compared with CTX group, LJP fractions, especially for LJP-A (200 mg kg-1) can enhance the immune function, improve atrophy of the lymphoid organs thymus and spleen (the increased approximately 1.8- and 1.6-fold), increase the phagocytic function of macrophages (increased approximately 1.7-fold), increase the secretion of cytokines (the levels of IL-6, IL-2, and TNF-α increased approximately 2.5-, 2.0-, and 1.4-fold) and immunoglobulins levels (the levels of IgM and IgG increased approximately 1.2- and 1.7-fold) in serum, and enhance the cytotoxic activity of NK cells (increased approximately 3.5-fold). Taken together, the present results suggest that LJP-A, rich in uronic acid, with a molecular weight of 400 kDa, may be a potential candidate as the functional foods.

Calcium Signaling Regulated by Cellular Membrane Systems and Calcium Homeostasis Perturbed in Alzheimer's Disease.

Although anything that changes spatiotemporally could be a signal, cells, particularly neurons, precisely manipulate calcium ion (Ca2+) to transmit information. Ca2+ homeostasis is indispensable for neuronal functions and survival. The cytosolic Ca2+ concentration ([Ca2+]CYT) is regulated by channels, pumps, and exchangers on cellular membrane systems. Under physiological conditions, both endoplasmic reticulum (ER) and mitochondria function as intracellular Ca2+ buffers. Furthermore, efficient and effective Ca2+ flux is observed at the ER-mitochondria membrane contact site (ERMCS), an intracellular membrane juxtaposition, where Ca2+ is released from the ER followed by mitochondrial Ca2+ uptake in sequence. Hence, the ER intraluminal Ca2+ concentration ([Ca2+]ER), the mitochondrial matrix Ca2+ concentration ([Ca2+]MT), and the [Ca2+]CYT are related to each other. Ca2+ signaling dysregulation and Ca2+ dyshomeostasis are associated with Alzheimer's disease (AD), an irreversible neurodegenerative disease. The present review summarizes the cellular and molecular mechanism underlying Ca2+ signaling regulation and Ca2+ homeostasis maintenance at ER and mitochondria levels, focusing on AD. Integrating the amyloid hypothesis and the calcium hypothesis of AD may further our understanding of pathogenesis in neurodegeneration, provide therapeutic targets for chronic neurodegenerative disease in the central nervous system.

Population data and phylogenetic structure of 19 STR loci in Chinese Hui ethnic group residing in Yunnan province of China.

Allele frequency distributions and statistical forensic parameters of 19 autosomal STR loci in a sample of 535 unrelated healthy Hui individuals from Yunnan province were estimated. A total of 236 alleles at these loci were identified and their corresponding allele frequencies ranged from 0.000935 to 0.527103. Penta E is the most informative in Hui population, whereas TPOX showed the lowest. All of the STR loci reached the Hardy-Weinberg equilibrium after Bonferroni correction. The combined discrimination power and probability of excluding paternity of the 19 STR loci were 0.999 999 999 999 999 999 999 984 47 16 and 0.999 999 988, respectively. Furthermore, the genetic relationship between the Yunnan Hui population and other 8 different Hui groups or 25 previously investigated groups residing in other areas of China were also estimated based on pairwise genetic distance. These results suggest that the 19 STR loci are highly polymorphic, which is suitable for forensic personal identification and paternity testing.

Identification of the structural features of quinazoline derivatives as EGFR inhibitors using 3D-QSAR modeling, molecular docking, molecular dynamics simulations and free energy calculations.

Epidermal growth factor receptor (EGFR) is a promising target for the treatment of different types of malignant tumors. Therefore, a combined molecular modeling study was performed on a series of quinazoline derivatives as EGFR inhibitors. The optimum ligand-based CoMFA and CoMSIA models showed reliable and satisfactory predictability (with R2cv=0.681, R2ncv=0.844, R2pred=0.8702 and R2cv=0.643, R2ncv=0.874, R2pred=0.6423). The derived contour maps provide structural features to improve inhibitory activity. Furthermore, the contour maps, molecular docking, and molecular dynamics (MD) simulations have good consistency, illustrating that the derived models are reliable. In addition, MD simulations and binding free energy calculations were also carried out to understand the conformational fluctuations at the binding pocket of the receptor. The results indicate that hydrogen bond, hydrophobic and electrostatic interactions play significant roles on activity and selectivity. Furthermore, amino acids Val31, Lys50, Thr95, Leu149 and Asp160 are considered as essential residues to participate in the ligand-receptor interactions. Overall, this work would offer reliable theoretical basis for future structural modification, design and synthesis of novel EGFR inhibitors with good potency.Communicated by Ramaswamy H. Sarma.

A novel prognostic signature for idiopathic pulmonary fibrosis based on five-immune-related genes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a highly fatal lung disease of unknown etiology with a median survival after diagnosis of only 2-3 years. Its poor prognosis is due to the limited therapy options available as well as the lack of effective prognostic indicators. This study aimed to construct a novel prognostic signature for IPF to assist in the personalized management of IPF patients during treatment. METHODS: Differentially-expressed genes (DEGs) in IPF patients versus healthy individuals were analyzed using the "limma" package of R software. Immune-related genes (IRGs) were obtained from the ImmPort database. Univariate Cox regression analysis was adopted to screen significantly prognostic IRGs for IPF patients. Multiple Cox regression analysis was used to identify optimal prognostic IRGs and construct a prognostic signature. RESULTS: Compared with healthy individuals, there were a total of 52 prognosis-related DEGs in the bronchoalveolar lavage (BAL) samples of IPF patients, of which 37 genes were identified as IRGs. Of these, five genes (CXCL14, SLC40A1, RNASE3, CCR3, and RORA) were significantly associated with overall survival (OS) in IPF patients, and were utilized for establishment of the prognostic signature. IPF patients were divided into high- and low-risk groups based on the prognostic signature. Marked differences in the OS probability were observed between high- and low-risk IPF patients. The area under curves (AUCs) of the receiver operating characteristic (ROC) curve for the prognostic signature in the training and validation cohorts were 0.858 and 0.837, respectively. The expression levels between RNASE3 and SLC40A1 (P<0.01, r=0.394), between RORA and CXCL14 (P<0.01, r=-0.355), between CCR3 and CXCL14 (P<0.01, r=0.258), as well as between RNASE3 and CCR3 (P<0.01, r=0.293) were significantly correlated. CONCLUSIONS: We developed a validated and reproducible IRG-based prognostic signature that should be helpful in the personalized management of patients with IPF, providing new insights into the relationship between the immune system and IPF.

Molecular characterization, expression and function analysis of Epinephelus coioides MKK4 response to SGIV and Vibrio alginolyticus infection.

Mitogen-activated protein kinase 4 (MKK4), a member of the MAP kinase family, play important roles in response to many environmental and cellular stresses in mammals. In this study, three MKK4 subtypes, EcMKK4-1, EcMKK4-2 and EcMKK4-3, were obtained from grouper Epinephelus coioides. The open reading frame (ORF) of EcMKK4s are obtained and the EcMKK4s proteins contain highly conserved domains: a S_TKc domain, a canonical diphosphorylation group and two conserved MKKK ATP binding motifs, Asp-Phe-Gly (DFG) and Ala-Pro-Glu (APE). EcMKK4s could be found both in the cytoplasmic and nuclear. The EcMKK4s mRNA were detected in all E. coioides tissues examined with the different expression levels, and the expression were up-regulated during SGIV (Singapore grouper iridescent virus) or Vibrio alginolyticus infection. EcMKK4 could significantly reduce the activation of AP-1 reporter gene. The results suggested that EcMKK4s might play important roles in pathogen-caused inflammation.

The Role of Filial Piety in the Relationships between Work Stress, Job Satisfaction, and Turnover Intention: A Moderated Mediation Model.

In China, filial piety, which usually refers to showing respect and obedience to parents, has exerted an important effect in the relationship between work stress and turnover intention. However, the mechanism behind this effect is still unclear. To address this gap in the existing literature, we developed and tested a moderated mediation model of the relationship that work stress shares with job satisfaction and turnover intention. In accordance with the dual filial piety model and the stress-moderation model, our hypothesized model predicted that the mediating effect of job satisfaction on the relationship between work stress and turnover intention would be moderated by reciprocal filial piety (RFP) and authoritarian filial piety (AFP). The analytic results of data that were obtained from 506 employees of manufacturing industries in China supported this model. Specifically, RFP and AFP, as a contextualized personality construct, positively moderated the direct relationship between work stress and turnover intention as well as the corresponding indirect effect through job satisfaction. In particular, RFP and AFP strengthened the positive effect of work stress on turnover intention. Based on these findings, recommendations to help employees fulfill their filial duties and reduce the effect of work stress on turnover intention among employees of Chinese manufacturing industries are delineated.

The Clinical Characteristics and Treatment Considerations for Intracranial Aneurysms Associated With Middle Cerebral Artery Anomalies: A Systematic Review.

Background: As a result of their low incidence, most of the studies on intracranial aneurysms associated with middle cerebral artery (MCA) anomalies were presented as case reports or small case series. No systematic review on this specific entity has been conducted. Methods: A PubMed search of the published studies was performed on April 6th, 2019 for patients who had intracranial aneurysms associated with MCA anomalies. The languages included in this study were English, Chinese, and Japanese. Results: Finally, 58 articles reporting of 67 patients including 1 case in our center were included. The identified patients (37 females, 55.2%) aged from 4 to 81 (49.85 ± 15.22) years old. 50 (50/67, 74.6%) patients presented with hemorrhagic stroke either from the MCA anomalies associated aneurysms or other sources. 63 aneurysms (63/67, 94.0%) were saccular, 3 (4.5%) were dissecting or fusiform, and 1 (1.5%) was pseudoaneurysm. 32 (32/65, 49.2%) patients had other concurrent cerebrovascular anomalies. 56 (83.6%) patients underwent open surgeries, 8 (11.9%) patients underwent endovascular treatment, and 3 (4.5%) patients were conservatively managed. 56 (56/61, 91.8%) patients achieved a good recovery. Conclusions: The pathophysiological genesis of intracranial aneurysms associated with MCA anomalies is still obscure. The inflicted patients tend to have other concurrent cerebrovascular anomalies, which denotes that congenital defect in cerebrovascular development might play a role in this process. Most of the affected patients could experience a good recovery after treatment.

Intracranial Dural Arteriovenous Fistulas With Brainstem Engorgement: An Under-Recognized Entity in Diagnosis and Treatment.

Background: In rare circumstances, patients with intracranial (dural arteriovenous fistulas) DAVFs could be complicated with brainstem engorgement, which might lead to delayed or false diagnosis and subsequent improper management. Methods: On July 2th, 2019, a systematic search was conducted in the PubMed database for patients with intracranial DAVFs complicated with brainstem engorgement. Results: Sixty-eight articles reporting of 86 patients were included for final analysis. The patients were aged from 20 to 76 years (57.10 ± 12.90, n = 82). The female to male ratio was 0.68 (35:51). Thirty-three (40.2%, 33/82) patients were initially misdiagnosed as other diseases. The specific location distributions were cranio-cervical junction, cavernous sinus, superior petrosal sinus, transverse and/or sigmoid sinus, tentorium, and other sites in 27 (32.5%), 11 (13.2%), 9 (10.8%), 10 (12.0%), 21 (25.3%), and 5 (6.0%) patients, respectively. The Cognard classification of DAVFs were II, III, IV, and V in 9 (10.7%, 9/84), 1 (1.2%, 1/84), 1 (1.2%, 1/84), and 73 (86.9%, 73/84) patients. Eighteen (22%, 18/82) patients were demonstrated to have stenosis or occlusion of the draining system distal to the fistula points. The mean follow-up period was 7.86 (n = 74, range 0-60 months) months. Fifty-four (70.1%, 54/77) patients experienced a good recovery according to the mRS score. Conclusions: Intracranial DAVFs complicated with brainstem engorgement are rare entities. Initial misdiagnosis and delayed definite diagnosis are common in the past three decades. The treatment outcome is still unsatisfactory at present. Early awareness of this rare entity and efficiently utilizing the up to date investigations are of utmost importance.

Efficacy and tolerability of paroxetine in adults with social anxiety disorder: A meta-analysis of randomized controlled trials.

OBJECTIVE: The present study aimed to estimate the comprehensive efficacy and tolerability of paroxetine in adult patients with social anxiety disorder (SAD). METHODS: We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for eligible randomized controlled trials (RCTs). The efficacy outcome was the mean change of different kinds of scale scores as well as response and remission rates. The secondary outcome was tolerability, defined as the discontinuation rate and the incidence of adverse events (AEs). RESULTS: Our meta-analysis included 13 RCTs. Mean changes in the Liebowitz Social Anxiety Scale (LSAS) total score, fear and avoidance subscale of LSAS scores were all significantly greater in patients with SAD that received paroxetine compared to those received placebo (total: MD = 13.46, 95%CI 10.59-16.32, P < .00001; fear: MD = 6.76, 95%CI 4.89-8.62, P < .00001; avoidance: MD = 6.54, 95%CI 4.63-8.45, P < .00001). Response and remission rates were both significantly greater in patients with SAD that received paroxetine compared to those received placebo (response: OR = 3.02, 95%CI 2.30-3.97, P < .00001; remission: OR = 3.14, 95%CI 2.25-4.39, P < .00001). There was no significant difference in discontinuation rate due to any reason between two groups (OR = 1.06, 95%CI 0.81-1.39, P = .65). Discontinuation rate due to AEs was higher in paroxetine than placebo group (OR = 3.41, 95%CI 2.45-4.72, P < .00001) whereas the rate due to lack of efficacy was higher in placebo as compared with paroxetine group (OR = 0.14, 95%CI 0.09-0.22, P < .00001). The incidence of any AE was significantly increased in patients that received paroxetine (OR = 1.83, 95%CI 1.43-2.35, P < .00001). CONCLUSION: Paroxetine was an effective and well-tolerated treatment option for adult patients with SAD.

Circulating MiR-29a, Possible Use as a Biomarker for Monitoring IgA Nephropathy.

INTRODUCTION: Previous studies have shown that TGF-ß1/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. To date, only few studies have reportedon circulating microRNAs in IgA nephropathy (IgAN). However, the plasma expression of miR-29a and its role in patients with IgAN remains unclear. In this study, we attempted to elucidate whether plasma miR-29a expression can be used as a biomarker for monitoring disease states. METHODS: For this study, 15 healthy subjects, 36 patients with untreated renal biopsy-proven IgAN, and 79 patients with IgAN, who were under treatment for a period of 1 year on an average, all of whom had similar age and gender distributions, were included. The plasma expression of miR-29a in each group was explored by real-time PCR, and the relationship between miR-29a expression and clinical, pathological, and prognostic indicators of IgAN was further evaluated. RESULTS: Relative plasma expression of miR-29a in patients with IgAN was significantly lower than that in healthy controls (P < .001), and these changes in plasma miR-29a could be suppressed by treatment (P < .05). Plasma miR-29a was positively correlated with eGFR and negatively correlated with proteinuria and serum creatinine, irrespective of whether or not the patients with IgAN accepted treatment (P < .05). Plasma miR-29a level was negatively correlated with primary pathological parameters such as crescent formation, Lee's and Oxford classification (P < .05). Kaplan-Meier analysis revealed that patients with high plasma expression of miR-29a had better renal function and better response to treatment compared to those with low expression (P < .05). CONCLUSION: Plasma miR-29a could be considered as a biological marker that reflects renal damage and function, to predict the progression of IgAN.