A new coronavirus associated with human respiratory disease in China.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

Author Correction: A new coronavirus associated with human respiratory disease in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency.

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation.

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1 . Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.

Evaluation of ST6Gal1 expression and clinicopathological significance in human glioma.

Glioma is the most common brain tumor, accounting for a large majority of cancer-related deaths. ß-galactoside α2, 6 sialyltranferase 1 (ST6Gal1), the primary enzyme responsible for the conjugation of α2, 6 sialic acids to protein and lipid targets, is strongly associated with the occurrence and development of several brain tumor types. Still, the expression, targets, and functions of ST6Gal1 in glioma patients remain undetermined. As sialylation of the Ig-like cell adhesion family molecules have prominent roles in the latter's regulation in other biological contexts, we screened for members that have potential to be regulated by ST6Gal1 in silico and examined co-expressed protein modules using data derived from the Cancer Genome Atlas (TCGA) database, and we identified neural cell adhesion molecule (NCAM1) as a major ST6Gal1-interacting target. Bioinformatic binding analysis confirmed the interaction of ST6Gal1 and NCAM1. Immunohistochemistry was then used to evaluate post-operative samples from 156 patients with gliomas. ST6Gal1 and NCAM1 were co-expressed in gliomas, and their expression correlated significantly (p = 0.002) by univariate analysis. Our study also found that the expression levels of both ST6Gal1 and NCAM1 corresponded negatively with glioma grade, isocitrate dehydrogenase (IDH) mutation, and proliferation index (Ki67). Consistently, Kaplan-Meier survival curves showed that lower ST6Gal1 and NCAM1 protein levels are linked to unfavorable outcomes in glioma patients (p = 0.018 and p < 0.001, respectively). Our data indicate that ST6Gal1 may participate in the inhibition of oncogenesis and malignant progression via interacting with and targeting NCAM1 in glioma, thus presenting a novel strategy for intervention.

Effect of neuromuscular electrical stimulation in critically ill adults with mechanical ventilation: a systematic review and network meta-analysis.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is widely used as a rehabilitation methods to restore muscle mass and function in prolonged immobilization individuals. However, its effect in mechanically ventilated patients to improve clinical outcomes remains unclear. METHODS: A comprehensive search was conducted using PubMed, Embase, Web of Science, PEDro, and the Cochrane Library from their inception until December 24th, 2023. The search targeted randomized controlled trials (RCTs) comparing NMES with physical therapy (PT) or usual ICU care (CG), for improving clinical outcomes in mechanically ventilated patients. We performed a network meta-analysis utilizing Stata version 14.0 and R 4.3.1. RESULTS: We included 23 RCTs comprising 1312 mechanically ventilated adults. The treatments analyzed were NMES, PT, NMES combined with PT (NMES+PT), and CG. Network meta-analyses revealed that NMES or NMES+PT significantly improved extubation success rate compared to CG, with ORs of 1.85 (95% CI: 1.11, 3.08) and 5.89 (95% CI: 1.77, 19.65), respectively. Additionally, NMES exhibited a slight decrease in extubation success rate compared with NMES+PT, with OR of 0.31 (95% CI: 0.11, 0.93). Nevertheless, neither NMES nor NMES+PT showed any significant improvement in ICU length of stay (LOS), ventilation duration, or mortality when compared with PT or CG. NMES+PT emerged as the most effective strategy for all considered clinical outcomes according to the ranking probabilities. The evidence quality ranged from "low" to "very low" in this network meta-analysis. CONCLUSIONS: NMES appears to be a straightforward and safe modality for critically ill, mechanically ventilated patients. When combined with PT, it significantly improved the extubation success rate against standard ICU care and NMES alone, and showed a better ranking over PT or NMES alone for clinical outcomes. Therefore, NMES combined with PT may be a superior rehabilitation strategy for this patient group.

Long-term trends and risk factors of tracheostomy and decannulation in patients with cervical spinal cord Injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the risk factors of tracheostomy and decannulation after cervical spinal cord injury (CSCI) and their epidemiological changes over the past 8 years in Beijing Bo'ai Hospital, China Rehabilitation Research Center (CRRC), China. SETTING: Beijing Bo'ai Hospital, CRRC. METHODS: We reviewed 8 years of patient data (2013.1.1 to 2020.12.31) at CRRC, focusing on those hospitalized and diagnosed with CSCI. We analyzed changes in demographic and clinical data's trends. Logistic regression analysis was used to determine factors impacting tracheostomy and decannulation. RESULTS: Finally, 1641 CSCI patients met the inclusion criteria. Over the past 8 years, the proportion of tracheostomized patients with CSCI was 16.3%, and the proportion of successfully decannulated of tracheostomized patients with TCSCI was 77.9%. We found that Traumatic (OR = 1.8, 95% CI = 1.06, 3.22; p = 0.046), Motor level of injury (C5-C8) (OR = 0.32, 95% CI = -1.91,-0.34; p = 0.005), AIS = A/B/C (OR = 22.7/11.1/4.2, 95% CI = 12.16,42.26/5.74,21.56/2.23,7.89; p < 0.001/p < 0.001/p < 0.001), age > 56 (OR = 1.6, 95% CI = 1.04, 2.32; p = 0.031) were the risk factors for tracheostomy. By analyzing the risk factors of decannulation failure in tracheostomized patients with TCSCI through multivariable logistic regression, statistically significant differences were found in age > 45 (OR = 4.1, 95% CI = 1.44, 11.81; p = 0.008), complete injury (OR = 2.7, 95% CI = 1.26, 5.95; p = 0.011), facet dislocation (OR = 2.8, 95% CI = 1.13,7.07; p = 0.027). CONCLUSIONS: Recent years have witnessed shifts in the epidemiological characteristics of CSCI. Identifying the factors influencing tracheostomy and decannulation in CSCI can aid in improving patient prognosis.

M2e-specific antibodies protect against influenza PR8 virus in an isotype and route dependent manner.

The ectodomain of influenza matrix protein 2 (M2e) is a promising target for the development of universal prophylactic and therapeutic agents against influenza viruses of different subtypes. We constructed three M2e-specific monoclonal antibody variants, M2A1-1 (IgG1), M2A1-2a (IgG2a), M2A1-2b (IgG2b), which have the same Fab region targeting the M2e epitope but different isotypes, and compared their protective efficacy in influenza PR8-infected mice. We found that anti-M2e antibodies provided protection against influenza virus in a subtype-dependent manner, with the IgG2a variant providing significantly better protection with lower virus titers and milder lung injury than IgG1 and IgG2b isotypes. Additionally, we observed that the protective efficacy was dependent on the administration routes, with intranasal administration of antibody providing better protection than intraperitoneal administration. The timing of administration was also critical in determining the protective efficacy; while all the antibody isotypes provided protection when administered before influenza challenge, only IgG2a provided minimal protection when the antibodies were administered after virus challenge. These results provide valuable information for optimizing the therapeutics usage of M2e-based antibodies and furthering the development of M2e-based universal influenza vaccines.

Development and Validation of Prognostic Nomograms for Lung Squamous Cell Carcinoma With Brain Metastasis in Patients Aged 45 Years or Older: A Population-Based Study.

PURPOSE: We aimed to establish nomograms to predict the survival in patients aged ≥45  years with lung squamous cell carcinoma and brain metastasis. METHODS: We collected patients diagnosed as lung squamous cell carcinoma with brain metastasis aged ≥45 years between 2010 and 2019 from the Surveillance, Epidemiology, and End Results database. Prognostic factors were determined by the univariate and multivariate Cox regression analysis, and then the nomogram was constructed to predict cancer-specific survival and overall survival. Nomograms were evaluated by decision curve analysis, the area under the receiver operating characteristic curve, calibration plot, concordance index, and risk group stratification. RESULTS: In total, 2437 patients were included, with 1706 and 731 in the cohorts of training and validation, respectively. The age, N stage, T stage, liver metastasis, chemotherapy, bone metastasis, along with radiotherapy were significant in predicting the survival, and adopted for the establishment of nomograms. In the training and validation sets, the concordance index were .713(95%CI:0.699-.728) & .700(95%CI:0.677-.722) in predicting cancer-specific survival and .715(95%CI:0.701-.729) & .712(95%CI:0.690-.735) in predicting overall survival, respectively. Besides, the area under the receiver operating characteristic curve for predicting cancer-specific survival and overall survival in the training set were all >.7 at 1-, 2-, and 3- years. Calibration plots proved the survival predicted by nomograms were consistent with the actual values. decision curve analysis revealed better clinical validity of the nomogram in predicting cancer-specific survival and overall survival at 1-year than TNM staging. Patients were stratified into the high-/low-risk groups according to the optimal cutoff value of 100.21 for cancer-specific survival and 91.98 for overall survival. A web-based probability calculator was constructed finally. CONCLUSION: Two nomograms were developed for the prognostic prediction of lung squamous cell carcinoma patients with brain metastasis aged ≥45 years, providing guidance for decision-making in clinical practice.

Comparison of early and late postoperative outcomes between chordal reconstruction and quadrangular resection in patients with posterior mitral valve prolapse: a single-center retrospective study.

BACKGROUND: To compare the early and late postoperative outcomes of chordal reconstruction (CR) and quadrangular resection (QR) in patients with posterior mitral valve prolapse (PMPL). METHODS: Between January 2008 and December 2018, 305 patients with PMPL who underwent mitral valve plasty (MVP) were included in this retrospective analysis. The CR and QR procedures were performed in 169 patients (CR group) and 136 patients (QR group), respectively. Early and late postoperative outcomes were compared between the groups. RESULTS: Follow-up was complete in 96.4% (294/305) of patients, with a mean follow-up of 81.2 ± 30.4 months. No 30-day mortality was observed in any of the patients. The success rate of the mitral valve repair was similar in both groups (99.4% vs. 98.5%, P = 0.850). The incidence of early postoperative hemolysis was lower in the CR group than in the QR group (0.00% vs. 3.0%, P = 0.024). Postoperative left ventricular end-diastolic diameter (LVEDD) decreased more significantly in the CR group than in the QR group at 3 months (8.15 [1.30,12.65] vs. 3.25 [- 0.05, 8.75] mm, P < 0.001). During follow-up, the overall survival rates were 95.1% and 94.6% in the CR and QR groups, respectively. The incidence of reoperation for moderate or severe mitral regurgitation (MR) was similar in both groups (4.3% vs.5.4%, P = 0.653), but the time interval between the initial operation and reoperation was shorter in the QR group than in the CR group (84.3 ± 36.1 vs. 120.9 ± 27.6 months, P = 0.026). The LVEDD enlargement was more significant in the QR group than in the CR group (4.5 [3.6, 4.5] vs. 2.4 [1.3, 2.8] mm, P < 0.001). CONCLUSION: CR and QR are effective techniques for patients with PMPL. Both techniques resulted in a low incidence of recurrent MR. However, CR can reduce early postoperative hemolysis and LVEDD more significantly. During the long-term follow-up, reoperations due to recurrent MR were performed at a longer interval after the initial operation. LVEDD expansion was better avoided in the CR group.

Rare renal cell carcinoma with haemangioblastoma-like features and leiomyomatous stroma: report of a unique case with TSC2 and SETD2 variations.

BACKGROUND: Renal cell carcinoma (RCC) with haemangioblastoma-like characteristics is a type of RCC reported in recent years. RCC with (angio) leiomyomatous stroma (RCCLMS) was included as a provisional entity of the 2016 World Health Organization (WHO) classification. RCC with haemangioblastoma-like characteristics and leiomyomatous stroma is extremely rare. This is the first report of a rare tumour harbouring TSC2 and SETD2 variations. CASE PRESENTATION: The patient was a 38-year-old woman who presented with discomfort in the area of her right kidney. Ultrasound and enhanced CT showed a right renal mass, and clear cell renal cell carcinoma (CCRCC) was suspected; hence, robot-assisted laparoscopic nephron-sparing partial nephrectomy was performed. Gross examination revealed a well-circumscribed tumour measuring 2.0 cm × 1 cm × 0.7 cm under the renal capsule adjacent to the stripping edge that was greyish yellow and greyish red in colour. Histologic examination showed that the tumour consisted of three different structures: a CCRCC-like region, a haemangioblastoma-like region, and a focal leiomyomatous stroma component. Based on immunohistochemistry, the CCRCC-like region was diffusely strongly positive for AE1/AE3, vimentin, CAIX, PAX8, PAX2, CK7, and CAM5.2, partly positive for HNF1α, and negative for CD10, α-inhibin, NSE, S-100, CD34, and TFE3. The haemangioblastoma-like area was diffusely positive for vimentin, CAIX; partly positive for PAX8, PAX2, α-inhibin, and S-100; mostly positive for NSE; and slightly positive for HNF1α; the CD34 staining highlighted the complex capillary network. The Ki67 index was approximately 1-2% in the two above areas, and the leiomyomatous stroma was strongly positive for SMA. The whole-exon sequencing (WES) showed TSC2 and SETD2 variations. There was no progression after 18 months of follow-up. CONCLUSION: We report for the first time a unique case of RCC with haemangioblastoma-like features and leiomyomatous stroma accompanied by rare molecular abnormalities. Whether this is a new tumour entity or a variant of clear cell carcinoma remains to be determined. The biological behaviour and clinical characteristics need to be further examined.

[Meta-analysis of efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine in treatment of chronic urticarial].

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.

ATF-3/miR-590/GOLPH3 signaling pathway regulates proliferation of breast cancer.

BACKGROUND: Breast cancer is one of the leading causes of death in women worldwide. Fast growth is the important character of breast cancer, which makes sure the subsequent metastasize and invasion breast cancer. Golgi related genes GOLPH3 has been reported to regulate many kinds of cancers proliferation. However, its upregulator remains largely unknown. miRNA modulate gene expression by post-transcriptional repression to participate in many signaling pathway of breast cancer cell proliferation. miR-590 has been reported to regulate tumorgenesis and could be regulated by its own target ATF-3. But whether miR-590 can be the modulator of Golgi related genes to regulate the breast cancer proliferation is unclear. METHODS: We performed the bioinformatics analysis of survival rate and expression differences of patients using the data of The Cancer Genome Atlas (TCGA).Both of MTS and BrdU assays were used for cell proliferation analysis. Cell cycle was detected by flow cytometry .qRT-PCR was used for detecting the cell cycle related gene expression. Student's t-test or One way anova was used for statistics. RESULTS: We found the upregulation of GOLPH3 in breast cancer samples compared with normal breast tissues, which also was related to the poor prognosis. Overexpression of GOLPH3 significantly promoted proliferation both of MDA-MB-231 cells (ER negative) and MCF-7 cells (ER positive). We further found that miRNA-590-3p could directly target the 3'-UTR of GOLPH3 mRNA to repress its expression. Overexpression of miR-590-3p inhibited the proliferation of MDA-MB-231 and MCF-7 cells. The rescue experiments indicated that overexpression of GOLPH3 significantly resorted the proliferation inhibited by miR-590-3p. We also found that ATF-3 repressed miR-590-3p expression to modulate miR-590/GOLPH3 pathway to regulate breast cancer cells proliferation. CONCLUSIONS: This study not only suggests that the ATF-3/miR-590/GOLPH3 signaling pathway is critically involved in the proliferation of breast cancer cells, but provides a novel therapeutic target and new insight base on epigenetic regulation for future breast cancer diagnosis and clinical treatment.

Total Aortic Arch Reconstruction With Triple-Branched Stent Graft or Hemiarch Replacement for Acute Debakey Type I Aortic Dissection: Five-Years Experience With 93 Patients.

OBJECTIVE: We compared the outcomes of a new triple-branched stent graft reconstruction technique of total aortic arch with those of the conventional strategy of replacing the hemiarch during the surgical treatment of acute Debakey type I aortic dissection over five years. METHODS: Fifty-two patients with acute Debakey type I aortic dissection underwent ascending aorta replacement combined with triple-branched stent graft reconstruction of the aortic arch from June 2008 to February 2010. Concurrently, 41 cases of Debakey type I aortic dissection underwent ascending aorta replacement combined with hemiarch replacement. Both groups received hypothermic cardiopulmonary bypass and selective cerebral perfusion. RESULTS: Patient characteristics and in-hospital mortality of the two groups were similar. Postoperative data were not different between the groups. During the five years after surgery, there were no deaths in the stent graft group and three deaths in the hemiarch group. The late reinterventions/events during follow-up in the stent graft group were significantly less than those in the hemiarch group. On postoperative computed tomography, the aortic diameter of both groups was significantly reduced compared to the postoperative aortic diameter. There was no difference in diameter between one month and five years postoperatively in the stent graft group, although in the hemiarch group the diameter was significantly greater at five years than at one month postoperatively. CONCLUSION: The triple-branched stent graft reconstruction of the aortic arch is an effective and simplified procedure for the treatment of acute Debakey type I aortic dissection.

An alternative approach for repair of supracardiac and infracardiac total anomalous pulmonary venous drainage in neonates and infants: superior approach with caval transection.

Recently, the superior approach with transaction of the superior vena cava was introduced for the repair of supracardiac anomalies in adults. We developed a bidirectional right-angle venous cannula and placed it within the innominate vein to make the modified superior approach with the superior caval transection suitable for neonates and tiny infants. We applied this modified superior approach for the repair of infracardiac forms of total anomalous pulmonary venous drainage.

Myricetin Attenuates Depressant-Like Behavior in Mice Subjected to Repeated Restraint Stress.

Increasing evidence has shown that oxidative stress may be implicated in chronic stress-induced depression. Several flavonoids with anti-oxidative effects have been proved to be anti-depressive. Myricetin is a well-defined flavonoid with the anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective properties. The aim of the present study is to investigate the possible effects of chronic administration of myricetin on depressant-like behaviors in mice subjected to repeated restraint (4 h/day) for 21 days. Our results showed that myricetin administration specifically reduced the immobility time in mice exposed to chronic stress, as tested in both forced swimming test and tail suspension test. Myricetin treatment improved activities of glutathione peroxidase (GSH-PX) in the hippocampus of stressed mice. In addition, myricetin treatment decreased plasma corticosterone levels of those mice subjected to repeated restraint stress. The effects of myricetin on the brain-derived neurotrophic factor (BDNF) levels in hippocampus were also investigated. The results revealed that myricetin normalized the decreased BDNF levels in mice subjected to repeated restraint stress. These findings provided more evidence that chronic administration of myricetin improves helpless behaviors. The protective effects of myricetin might be partially mediated by an influence on BDNF levels and might be attributed to myricetin-mediated anti-oxidative stress in the hippocampus.

[Clinical evaluation of percutaneous atrial septal defect closer guided by transthoracic echocardiography and/or transesophageal echocardiography].

OBJECTIVE: To evaluate the safety and efficacy of percutaneous closure of the single secundum atrial septal defects (ASD) guided by transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE).
 METHODS: From January, 2014 to December, 2014, thirty-two patients with single secundum ASD from Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, were treated with percutaneous closure of ASD guided by TTE or TEE.
 RESULTS: Thirty-two patients underwent ASD closure successfully, except one patient showed trivial residual shunts, which disappeared one month later. The remaining 31 patients were subjected to TTE. At once or at the 1st or 3rd month after the procedure, no ASD migration or residual shunts were observed.
 CONCLUSION: Percutaneous closure of ASD guided by TTE or TEE is a safe and effective surgery method with minimal invasion and can avoid the chest incision and radioscopy.

The association between the phenotype of excessive daytime sleepiness and blood pressure in patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: Investigate the clinical features and the blood pressure (BP) pattern of the phenotype of excessive daytime sleepiness (EDS) in OSAHS. METHODS: A total of 508 Chinese adults with suspected OSAHS were referred to our sleep laboratory from October 2009 to May 2012. On the same night of polysomnography (PSG), the levels of blood pressure were measured before sleeping (bedtime BP) and immediately after waking up in the next morning (morning BP). EDS was recognized as Epworth Sleepiness Scale (ESS)≥9. Subjects were classified into four groups based on the apnea-hypopnea index (AHI) from PSG as follows: control (simple snoring) group (control, n=104) with AHI<5; mild group (mild, n=89) with AHI≥5 and <15; moderate group (moderate, n=70) with AHI≥15 and<30; and severe group (severe, n=245) with AHI ≥30. The differences and correlations between BP and PSG parameters in EDS and non-EDS group of OSAHS patients were analyzed. RESULTS: In all subjects, ESS was positively correlated with morning diastolic blood pressure (DBP), Mean arterial pressure (MAP) and bedtime DBP (r=0.144, 0.102 and 0.114, respectively, each P value<0.05). In OSAHS patients, ESS was only positively correlated with morning DBP (r=0.137, P<0.05). OSAHS patients with EDS phenotype were younger and were more likely to have the symptom of waking up feeling tired (36.1% vs. 23.2%, p=0.023), who had lower MSaO2, longer SIT90 (the ratio of time of SpO2 below 90% in total sleep time) and higher DBP (bedtime as well as morning). In patients with AHI≥15, ESS was correlated positively with both bedtime and morning DBP after controlling the confounding effects of age, sex, BMI, AHI and nadir nocturnal oxygen saturation( r=0.126,0.143, respectively, both P values<0.05). And in OSAHS patients of EDS phenotype, the bedtime DBP, bedtime MAP, morning DBP, and morning MAP were 3~5 mm Hg higher than that in patients of non-EDS phenotype(P<0.05). In the moderate and severe OSAHS group, patients with EDS phenotype were younger and had a lower mean blood oxygen saturation (MSaO2), longer time of SpO2 below 90% and higher SIT90 than patients with non-EDS phenotype (P<0.05). In hypertensive OSAHS patients, patients with EDS were also younger and had higher micro-arousal index (MiI), as well as higher morning DBP, morning MAP and bedtime DBP than that in non-EDS group (P<0.05). CONCLUSIONS: EDS in OSAHS patients is a special phenotype, which was characterized by younger age, higher DBP and more severe hypoxic load. This feature is mainly manifested in moderate and severe OSAHS patients. It is very important to identify the phenotype of EDS in patients with OSAHS, who may meet more benefits from effective treatment of OSAHS by correcting the intermittent nocturnal hypoxia and sleep fragmentation.

[The expression of SIRT1 in brainstem of rats in different types of hypoxia and its significance].

OBJECTIVE: To explore the correlation between SIRT1 expression in brainstem and apnea hypopnea index and the effect of hypoxia on SIRT1 expression in rats. METHODS: Thirty-three healthy Sprague-Dawley(SD) rats underwent sleep monitoring and SIRT1 protein in brainstems was measured by Western blot. The correlation of sleep apnea index and SIRT1 protein level in brainstem was analysed. Another 36 adult male SD rats were randomly and equally divided into 4 groups: normal control (NC) group, continuous hypoxia (CH) group, intermittent hypoxia (IH) group and intermittent hypoxia with hypercapnia (IHH) group. The expression of SIRT1 protein of the lower brainstems of the 4 groups were measured by Western blot. RESULTS: The level of SIRT1 in the brainstem was negatively correlated with the frequency of spontaneous sleep apnea in REM(r = -0.617, P < 0.001) while positively correlated with the frequency of post sigh sleep apnea in REM (r = 0.535, P < 0.01). The relative expression level of SIRT1 in NC, CH, IH, IHH group were (1.4 ± 1.0), (1.4 ± 0.6), (2.5 ± 1.0) , (1.6 ± 1.2), respectively. There was a significant difference in the SIRT1 level among groups (F = 2.964, P < 0.05) . CONCLUSIONS: The rats with lower level of SIRT1 may have lower anti-oxidative stress capability which results in higher frequency of spontaneous sleep apnea. Under the circumstance of hypoxia, the fact that the expression of SIRT1 protein was elevated may be a protective mechanism.

Exploration of the shared diagnostic genes and mechanisms between periodontitis and primary Sjögren's syndrome by integrated comprehensive bioinformatics analysis and machine learning.

BACKGROUND: Accumulating evidence has showed a bidirectional link between periodontitis (PD) and primary Sjögren's syndrome (pSS), but the mechanisms of their occurrence remain unclear. Hence, this study aimed to investigate the shared diagnostic genes and potential mechanisms between PD and pSS using bioinformatics methods. METHODS: Gene expression data for PD and pSS were acquired from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were utilized to search common genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore biological functions. Three machine learning algorithms (least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF)) were used to further identify shared diagnostic genes, and these genes were assessed via receiver operating characteristic (ROC) curves in discovery and validation datasets. CIBERSORT was employed for immune cell infiltration analysis. Transcription factors (TFs)-genes and miRNAs-genes regulatory networks were conducted by NetworkAnalyst. Finally, relevant drug targets were predicted by DSigDB. RESULTS: Based on DEGs, 173 overlapping genes were obtained and primarily enriched in immune- and inflammation-related pathways. WGCNA revealed 34 common disease-related genes, which were enriched in similar biological pathways. Intersecting the DEGs with WGCNA results yielded 22 candidate genes. Moreover, three machine learning algorithms identified three shared genes (CSF2RB, CXCR4, and LYN) between PD and pSS, and these genes demonstrated good diagnostic performance (AUC>0.85) in both discovery and validation datasets. The immune cell infiltration analysis showed significant dysregulation in several immune cell populations. Regulatory network analysis highlighted that WRNIP1 and has-mir-155-5p might be pivotal co-regulators of the three shared gene expressions. Finally, the top 10 potential gene-targeted drugs were screened. CONCLUSION: CSF2RB, CXCR4, and LYN may serve as potential biomarkers for the concurrent diagnosis of PD and pSS. Additionally, we identified common molecular mechanisms, TFs, miRNAs, and candidate drugs between PD and pSS, which may provide novel insights and targets for future research on the pathogenesis, diagnosis, and therapy of both diseases.