Technical challenges in REM sleep microstructure classification: A study of patients with REM sleep behaviour disorder.

While commonly treated as a uniform state in practice, rapid eye movement sleep contains two distinct microstructures-phasic (presence of rapid eye movement) and tonic (no rapid eye movement). This study aims to identify technical challenges during rapid eye movement sleep microstructure visual classification in patients with rapid eye movement sleep behaviour disorder, and to propose solutions to enhance reliability between scorers. Fifty-seven sleep recordings were randomly allocated into three subsequent batches (n = 10, 13 and 34) for scoring. To reduce single-centre bias, we recruited three raters/scorers, with each trained from a different institution. Two raters independently scored each 30-s rapid eye movement sleep into 10â€…× fSEM3-s phasic/tonic microstructures based on the AASM guidelines. The third rater acted as an "arbitrator" to resolve opposite opinions persisting during the revision between batches. Besides interrater differences in artefact rejection rate, interrater variance frequently occurred due to transitioning between microstructures and moderate-to-severe muscular/electrode artefact interference. To enhance interrater agreement, a rapid eye movement scoring schematic graph was developed, incorporating proxy electrode use, filters and cut-offs for microstructure transitioning. To assess potential effectiveness of the schematic graph proposed, raters were instructed to systematically apply it in scoring for the third batch. Of the 34 recordings, 27 reached a Cohen's kappa score above 0.8 (i.e. almost perfect agreement between raters), significantly improved from the prior batches (p = 0.0003, Kruskal-Wallis test). Our study illustrated potential solutions and guidance for challenges that may be encountered during rapid eye movement sleep microstructure classification.

Probiotics: are they beneficial?

There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.

Isolation, identification, and evaluation of the biocontrol potential of a Bacillus velezensis strain against tobacco root rot caused by Fusarium oxysporum.

AIMS: Tobacco (Nicotiana tabacum) is an economically important crop. Root rot caused by Fusarium oxysporum has become a damaging disease in N. tabacum crops grown in Henan province of China. Therefore, the objectives of this study were to screen bacterial isolates against F. oxysporum from rhizosphere soils of tobacco growing areas and to evaluate their antifungal activities, biocontrol effects, and effects on plant growth. METHODS AND RESULTS: Nineteen strains with antifungal inhibition effects of >60% against F. oxysporum were obtained using the method of flat confrontation; the strain Ba-0321 was the strongest, with an antifungal effect of 75%. Moreover, this strain had broad spectrum antimicrobial activity to eight additional tobacco pathogens. The strain was identified as Bacillus velezensis by morphology and the 16S rDNA sequence. The B. velezensis strain Ba-0321 had strong UV resistance as well as tolerance to high temperatures and low nutrition. The bacteria inhibited spore germination and mycelial growth of F. oxysporum under in vitro co-culture conditions. In vivo assays demonstrated that the Ba-0321 strain significantly reduced the pathogenicity of F. oxysporum, resulting in a control effect on tobacco root rot of 81.00%. Simultaneously, the bacteria significantly promoted root development and the growth of tobacco plants. CONCLUSION: Our results confirmed that the B. velezensis strain Ba-0321 has a strong antifungal effect and stress resistance that enable it to be used as a biological control agent for tobacco root rot caused by F. oxysporum. SIGNIFICANCE AND IMPACT OF THE STUDY: Tobacco root rot caused by F. oxysporum has become a damaging disease in China. The B. velezensis strain Ba-0321 has promising application value for controlling tobacco root rot diseases, and it could provide a new biocontrol agent against root rot caused by F. oxysporum in other plant species.

[Review and perspective of clinical research involving chest tightness variant asthma in China].

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.

[Visualization analysis of research hotspots in pathogenesis of diabetic nephropathy in China].

The aim of this study is to analyze the research hotspots and development trends in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022. Based on China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database, China Biology Medicine disc, Web of Science core collection and PubMed database, the related literatures in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022, were retrieved to establish the database, and the VOSviewer software was used for bibliometric analysis. A total of 1 664 Chinese and 2 149 English literatures are included in this study. The scientific research results from 2013 to 2022 have shown an overall increasing trend. The research hotspots in the field of pathogenesis of diabetic nephropathy in China are mainly concentrated in Podocytes, Oxidative stress, Inflammation, Renal fibrosis, Urine protein, etc. The frontier hotspots in this field include Biomarkers, Nrf2, Gut microbiota, NLRP3 inflammasome, Apoptosis, MicroRNA, etc. Through visual analysis, the research hotspots and frontier trends of the pathogenesis of diabetic nephropathy in China can be visually presented, and then provide new ideas and directions for the further in-depth research on the pathogenesis of diabetic nephropathy.

[The effective analysis of refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer treated by endoscopic radiotomy combined with local injection of triamcinolone acetonide].

Refractor esophageal stenosis after endoscopic submucosal dissection of early esophageal carcinoma is a difficult clinical problem. To verify the effect of endoscopic radial incision combined local triamcinolone injection to treat refractory esophageal stenosis, we retrospectively analyzed 7 patients diagnosed with refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer in this study, of whom 4 male and 3 female patients, aged 50-76 years, with the mean age of 63 years. We performed the endoscopic radial incision in the thickness point of the scar stricture and injected the triamcinolone locally. The results showed it was safe and effective. The follow-up showed no esophageal stenosis occured and no adverse reaction such as hemorrhage, perforation, tumor-recurrence and triamcinolone-allergy occured.

[Progress of regulatory T cells in the regulation of anti-tuberculosis immunity].

Mycobacterium tuberculosis (MTB), as an intracellular parasitic bacterium, invades the human body mainly through droplets, which can lead to multiple organ infection, causing the body to produce T cell-dominated immunity to tuberculosis (TB). Regulatory T cells (Tregs), as a class of T lymphocyte subsets that negatively regulate the immune response of the body, play an important role in regulating immune balance in host anti-tuberculosis immunity. A large number of studies have shown that MTB-specific Tregs affects the occurrence and development of tuberculosis and the efficacy of the vaccine. Therefore, elucidating the role and regulatory mechanism underlying anti-MTB immune response of MTB-specific Tregs will help to further understanding of the decrease of host anti-MTB immune cell function, and provide a basis for the study of immunotherapy of TB. This paper briefly introduces the subtypes and functions of Tregs, and systematically reviews the research progress of Tregs in many fields of TB.

Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

[Efficacy of endovenous microwave ablation in treating primary varicose veins of the lower extremities].

Objective: To explore the efficacy of endovenous microwave ablation in treating primary varicose veins of the lower extremities. Methods: A total of 214 patients with primary varicose veins of the lower extremities in the First Affiliated Hospital of Sun Yat-sen University from January 2017 to November 2019 were included and divided into microwave ablation group (n=128) and high ligation with microwave ablation group (n=86) according to surgical approach. Further subgroups including subgroup S (diameter<10 mm) and subgroup L (diameter≥10 mm) were established. The surgical success rate, postoperative incidence and recovery of local skin numbness and ecchymosis, and the postoperative recovery of active skin ulcer were compared between the two groups and subgroups. Results: The surgical success rate was 96% (136/141) in microwave ablation group, 100% in subgroup S (116/116), and 80% in subgroup L (20/25), respectively. In addition, the surgical success rate in high ligation with microwave ablation group, subgroup S, and subgroup L was all 100% (90/90, 73/73, and 17/17). In subgroup L of microwave ablation group, the diameter of 5 great saphenous veins in patients who failed the microwave ablation was 13.0-17.1 mm. The mean follow-up time was (24±4) months in microwave ablation group and (36±6) months in high ligation with microwave ablation group, respectively. In the microwave ablation group and high ligation with microwave ablation group, the incidence of postoperative skin numbness was 15.6% and 14.4%, respectively, and the incidence of skin ecchymosis was 5.7% and 3.3%, respectively, with no statistically significant difference between the two groups (both P>0.05). The rate of active skin ulcer in the two groups was 6.4% and 15.6%, respectively, and the difference was statistically significant (P=0.020). Local skin ecchymosis in the two groups recovered within 1 month after operation. Local skin numbness in both groups recovered within the maximum 2 years of follow-up, and active skin ulcer in both groups recovered within the maximum 1 years of follow-up. Conclusion: The endovenous microwave ablation is safe and effective, especially combining with high ligation of great saphenous vein. Good follow-up results can be achieved for great saphenous vein with diameter smaller than 10 mm. However, for those with diameter greater than 10 mm, the surgical success rate of endovenous microwave ablation decreases.

[Preoperative treatment of uterine fibroids with low-dose mifepristone: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study].

Objective: To evaluate the clinical efficacy and safety of oral mifepristone (10 mg/day) versus placebo in the preoperative treatment of uterine fibroids. Methods: This study was a multi-center, randomized, double-blind, placebo, parallel controlled trial. A total of 132 patients with uterine fibroids were randomly divided into study group and control group, with 66 cases in each group. The patients in the study group orally took 1 tablet/day of mifepristone (dose of 10 mg/tablet), the patients in the control group orally took 1 tablet/day of placebo, and both groups were treated for 3 months. The primary efficacy evaluation indicators were the change rate of maximum fibroid volume; the secondary efficacy evaluation indicators included amenorrhea rate, improvement of subjective symptoms and anemia; the safety evaluation indicators included the analysis of adverse events and changes in laboratory biochemical indicators. Results: At the end of treatment, the maximum leiomyoma volume was reduced by 25.97% (95%CI: -34.79%--15.95%) in the study group and reduced by 1.51% (95%CI: -13.03%-11.54%) in the control group. The change rate of the maximum leiomyoma volume before and after treatment in the study group was significantly greater than that in the control group, and the difference in the change rate of the maximum leiomyoma volume between the two groups was -24.84% (95%CI: -36.56%--10.94%), which was much higher than the 10% superiority threshold goal set by this study within the 95%CI interval. At the end of treatment, the complete amenorrhea rate [84% (52/62)], dysmenorrhea elimination rate [98% (61/62)], and menstrual blood loss disappearance rate [87% (54/62)] in the study group were significantly higher than those in the control group (all P<0.05). At the end of treatment, the mean hemoglobin [(131±13) g/L], red blood cell count [(4.5±0.4)×1012/L] and hematocrit (0.39±0.03) in the study group were significantly increased compared with the baseline, and the differences had statistical significance (all P<0.05); after treatment, the differences in the above three indicators between the two groups had statistical significance (all P<0.01). The serum estradiol level in the study group was significantly lower than that in the control group at the end of treatment, and the difference was statistically significant (P<0.01). There were no significant differences in follicle-stimulating hormone and cortisol levels before and after treatment between the two groups (P>0.05). The overall incidences of any adverse event were not significantly different between the two groups (all P>0.05). Abdominal pain was the most common adverse event in the study group [9% (6/65)], but the incidence was not significantly increased compared with the control group [3% (2/64); P>0.05]. Conclusion: Compared with placebo, oral mifepristone 10 mg/day is significantly superior to placebo in reducing the size of uterine fibroids and improving anemia, without significant adverse reactions, and could be used as a drug treatment for patients with of uterine fibroids before surgery.

[Protective effect of baicalein on high fat-induced hepatocytes oxidative damage].

Objective: To investigate the effect of baicalein in improving non-alcoholic fatty liver disease caused by high fat-induced oxidative damage in mice. Methods: Male C57BL/6J mice weighing 18-20 g were randomly divided into 4 groups: normal control group (C, 10% fat for energy), high-fat group (H, 60% fat for energy), high-fat + scutellaria baicalein group (H+B, baicalein: 400 mg·kg(-1)·bw(-1)), and baicalein control group (B, baicalein: 400 mg·kg(-1)·bw(-1)). After 12 weeks, mice were sacrificed, and the tissue samples were collected. Liver pathological changes were observed by hematoxylin and eosin staining. Mitochondrial morphology was examined by ultramicropathology. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and mitochondrial membrane potential (MMP) changing levels in the liver were determined by kit. Sestrin2 and protein carbonylation (PCOS) levels were detected by Western blotting. Small interfering RNA (siRNA) was used to knock-down the Sestrin2 protein expression in HepG2 cells. Intramyocellular lipid changes in HepG2 cells was detected by fluorescent dye BODIPY493/503. One way ANOVA was used LSD pairwise comparison method was used to test the statistical difference. Results: Compared with the normal control group, high-fat fed caused significant fatty degeneration, decreased GSH and SOD levels (P ​​< 0.05), increased MDA and protein carbonylation levels, and increased Sestrin2 expression (P < 0.05) in mice. Mitochondrial shape changes, swelling, lack of cristae, and MMP was down-regulated by 33.3% (t = 13.456, P ​​< 0.001). Baicalein intervention had effectively inhibited hepatic steatosis and oxidative damage caused by high-fat fed, and further up-regulated Sestrin2 expression, MMP (t = 10.104, P ​​< 0.001), and significantly alleviated liver damage in mice. Sestrin2 expression knock-down had further increased the intracellular lipid deposition and PCOs expression (P ​​< 0.05), and reduced baicalein ability to antagonize lipid deposition and antioxidant capacity in Hep2 cells. Conclusion: Baicalein alleviate non-alcoholic fatty liver by regulating Sestrin2 expression and high-fat fed-induced liver oxidative damage.

Intravesical prostatic protrusion does not compromise the therapeutic effects of Mirabegron in male patients with overactive bladder.

AIMS: Intravesical prostatic protrusion (IPP) is associated with the degree of benign prostatic obstruction. We evaluated the effects of Mirabegron, a selective ß3 adrenoceptor agonist, on overactive bladder (OAB) in male patients with different degrees of IPP. METHODS: About 185 male patients ≥40 years with lower urinary tract symptoms were recruited from a tertiary referral center. OAB was defined by the overactive bladder symptom score (OABSS) urgency score of ≥2 and sum score of ≥3. IPP was measured in the midsagittal section using transrectal ultrasound and patients were divided into IPP ≤5 mm and IPP >5 mm groups. Outcomes were assessed at the baseline, 4, and 12 weeks. RESULTS: About 104 patients (56.2%) were diagnosed with OAB and received Mirabegron (50 mg) daily use. Both IPP groups (≤5 and >5 mm) had similar baseline OABSS and International Prostate Symptom Scores (IPSS). Four-week Mirabegron usage was associated with significant decreases in both symptom score measurements, OABSS: IPP ≤5 mm -27.4% and IPP >5 mm -19.7% (P = .419) and IPSS: -32% and -22.5% (P = .202), respectively. Urgency, urge incontinence, and nocturia sub-scores were decreased in both groups, -26.3% and -27.4% (P = .690), 53.3% and 46.2% (P = .916), and 20.8% and 15.4% (P = .958). Effects were maintained at 12 weeks. We found no significant improvement in the frequency sub-score in either group. One patient stopped medication because of intolerable hypertension. Most frequent adverse event was increased residual urine (≥50 mL higher than baseline), IPP ≤5 mm 9.2% and IPP >5 mm 5.1% (P = .707), but no case had acute urinary retention. CONCLUSIONS: Mirabegron is an effective drug to treat male OAB regardless of IPP grade.

[Application strategy and effect of cuffed tracheostomy tube with inner cannula in the treatment of postoperative complications of laryngeal or hypopharyngeal cancer].

Objective: To Investigate the application strategy and effect of cuffed tracheostomy tube with inner cannula in the treatment of postoperative complications of laryngeal and hypopharyngeal cancer. Methods: A total of 60 patients with laryngeal and hypopharyngeal cancer occurred serious postoperative complications, including 31 cases of severe postoperative neck infection, 8 cases of dyspnea, 5 cases of massive hemorrhage and 16 cases of seriously intractable aspiration. The tracheal cannula with inner cannula and outer cuff was immediately worn on these patients and the cuff was inflated. Different treatments were carried out according to different complications. The outer cuffs were inflated for patients with severe neck infections to prevent a large amount of neck secretions inhaled to the trachea. Patients with dyspnea immediately received ventilator-assisted ventilation. For those with massive hemorrhage on the wound, doctors should prevent bleeding and stop bleeding under general anesthesia. Patients with severely coughing should perform eating training to prevent food aspiration. The inner cannula was regularly replaced once a month for all of these patients. Results: Through targeted treatment, the complications of 60 patients with cuffed tracheostomy tube with inner cannula were effectively controlled. After dressing change, the neck wounds of 31 patients with neck infection were shrunk or healed. Finally, all of the patients were replaced with metal tracheal tubes. Eight cases with dyspnea were rescued with the symptomatic and related special treatment, and finally replace by metal tracheal tube. Five cases with massive bleeding in the neck wound were successfully rescued and replaced with metal tracheal cannula. Thirteen patients among 16 cases with intractable aspiration were removed the tracheal cannula and other 3 cases of old and severely ill were replaced with metal tracheal cannula. Conclusions: The cuffed tracheostomy tube with inner cannula is of great value in the treatment of severe postoperative complications of laryngeal or hypopharyngeal cancer. It is strongly recommended that the operators should fully understand and use it reasonably after the operation of laryngeal or hypopharyngeal cancer.

[Novel compound heterozygous LoF mutations in SRD5A2 may result in disorders of sex development].

Objective: To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients. Methods: In March 2019, a patient with gonadal dysplasia (hypospadias associated with cryptorchidism) was referred to Shanghai General Hospital. His secondary sex characters, level of sex hormones and the development of male reproductive system was assessed through physical examination, sex hormone examination, male reproductive system B-ultrasound and computed tomography (CT). Whole-exome sequencing (WES) was preformed to investigate the pathogenic genetic variations associated with hypospadias and cryptorchidism. Also, Sanger sequencing was conducted to verify the WES results in the pedigree. Semen analysis was used to assess the fertility of the proband and the SRD5A2 gene analysis of his spouse was performed to assess the risk of genetic defects in the offspring. Results: The patient suffered from gonadal dysplasia (hypospadias associated with cryptorchidism). Physical examination showed an inverted triangular distribution of pubic hair, small penis and the volume of the testis was 8 ml. Sex hormone examination revealed the level of FSH, LH, Pituitary prolactin (PRL), estrogen (E(2)), testosterone (T), and sex hormone-binding globulin (SHBG) was 25.81 U/L, 10.84 U/L, 21.09 µg/L, 153 pmol/L, 16.95 nmol/L, and 36.15 nmol/L respectively. B-ultrasound and computed tomography (CT) showed left inguinal testis. Also, semen analysis illustrated that the volume was 0.05 ml and sperm concentration<2×10(6)/ml, suggesting oligospermia in this case. WES sequencing and Sanger sequencing showed compound heterozygous LoF mutations in SRD5A2 [NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] in this patient. And there were no pathogenic genetic variations of SRD5A2 in the spouse. Conclusion: Novel compound heterozygous LoF mutations in SRD5A2[NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] may be the primary cause of disorders of sex development.

[Methodological considerations in the design of clinical trial for innovative hepatitis B drugs].

The research and development of innovative drugs targeting the clinical cure of chronic hepatitis B has become active in recent years. In the clinical trials of new drugs for hepatitis B, the use of new design concepts, new methods, and new technologies to evaluate the efficacy of innovative drugs is expected to shorten the clinical research process of candidate new drugs and reduce the cost of new drug development. However, the new designs such as seamless adaptive design and master plan design have few practical applications in clinical trials of innovative hepatitis B drugs. This article will focus on the methodological factors in the design of phase II/III clinical trials of innovative hepatitis B drugs, and introduce the key points of the new clinical trial design in order to provide methodological references for the development of innovative hepatitis B drugs.

[Mid- and long-term results of endovascular aneurysm repair for abdominal aortic aneurysms: a single center's experience for 10 years].

Objective: To examine the mid- and long-term outcomes of endovascular aneurysm repair (EVAR). Methods: This was a retrospective cohort study of 540 patients with abdominal aortic aneurysm who received EVAR at Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University from January 2009 to December 2018. There were 503 males and 37 females, aged of (69±8) years (range: 44 to 87 years). Clinical data including concomitant disease, aneurysm size and surgical data were collected and patients were followed up after operation. The cumulative survival rate was assessed using the Kaplan-Meier estimator and multivariate Cox regression was used to analyze the independent prognosis factors. Results: The technical success rate was 91.1% (492/540). The perioperative mortality rate was 1.3% (7/540) and the follow-up rate was 91.7% (489/533). The median follow-up time was 45(63) months (range: 1 to 133 months). The all-cause mortality rate was 21.3% (104/489) and the aneurysm-related mortality rate was 6.3% (31/489) during follow-up period. The overall cumulative survival rate of 1-, 3-, 5- and 10-year were 95.1%, 84.0%, 69.5% and 38.6%, respectively, while freedom from aneurysm-related death were 98.4%, 93.3%, 88.4% and 84.4%. During the follow-up period, the complications rate was 9.0% (44/489), and the re-intervention rate was 4.9% (24/489). Cox regression analysis showed that elder age (HR=2.15, 95%CI: 1.41 to 3.26, P<0.01), preoperative aneurysm rupture (HR=2.72, 95%CI: 1.78 to 4.15, P<0.01) and short neck aneurysm (HR=1.97, 95%CI: 1.07 to 3.61, P=0.029) were independent prognosis factors for long-term survival after EVAR. Connclusion: EVAR has low perioperative mortality, high technical success rate, and satisfactory mid-and long-term outcomes.

A novel mechanism of memory loss in Alzheimer's disease mice via the degeneration of entorhinal-CA1 synapses.

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECIIPN) directly innervate CA1 parvalbumin (PV) neurons (CA1PV) and are selectively degenerated in AD mice, which exhibit amyloid-ß plaques similar to those observed in AD patients. A loss of ECIIPN-CA1PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPN using a theta burst paradigm rescues ECIIPN-CA1PV synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECIIPN-CA1PV pathway.

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

[Cytomegalovirus active infection after kidney transplantation affecting the expression of activation receptor CD226 on NKT cell].

Objective: To investigate the effect of active cytomegalovirus infection post kidney transplant on the expressing of receptor CD226 on NKT cell. Methods: Case controlled study. From December 2013 to December 2014, 43 cases of kidney transplant recipient with CMV infection were collected in the Organ Transplantation Research Institute of the former 309th Hospital of PLA. The healthy control group included 15 cases. 15 cases of recipients who were stable after operation and followed up in our hospital at the same time were also collected as control. Peripheral blood specimen with EDTA as anticoagulant were used and analyzed by flow cytometry. Results: The population of NKT in CMV infection recipients were 5.19(1.18, 25.92)%, while in the remission stage the population were 4.89(0.68, 25.33)%, Compared with normal healthy controls and the stable recipients, the percentage of CD3(+)CD56(+) NKT cells in periphery blood mononuclear cells did not vary among these groups(P>0.05). The CD226(+) NKT population during the active CMV infection was (70±13)%, which was significantly lower than the health control [(87±10)%] and stable recipients [(80±9)%](P<0.001). Whereas in the CMV infection remission stage, the CD226(+)NKT population was (81±16)%, which was significantly higher than that of CMV active infection group (P<0.05), and showed no difference with the health control group and stable recipients (P>0.05). The CD226 MFI expressed on NKT in CMV infection group was 101±49, which showed no difference with health controls and stable recipients (P>0.05). However, significantly up regulation of CD226 MFI on NKT was observed in the samples obtained from the same recipients in CMV active infection (91±40) and in CMV regression stage(173±73)(P<0.001). Conclusions: The CD226(+) NKT cells population was down during the active CMV infection post kidney transplantation, while the expression of CD226 and the population of CD226(+)NKT could regression when the CMV infection regressed, which indicates the involvement of CD226 in the process of NKT cells anti-CMV infection.

Management of patients with incurable colorectal cancer: a retrospective audit.

AIM: Counselling patients and their relatives about non-curative management options in colorectal cancer is difficult because of a paucity of published data. This study aims to determine outcomes in patients unsuitable for curative surgery and the rates of subsequent surgical intervention. METHOD: This was an analysis of all colorectal cancers managed without curative surgery in a district general hospital from a prospectively maintained cancer registry between 2009 and 2016, as decided by a multidisciplinary team. Primary outcomes were overall survival and secondary outcomes were subsequent intervention rates and impact of tumour stage. RESULTS: In all, 183 patients out of 976 patients (18.8%) were identified. The median age at diagnosis was 81 years [interquartile range (IQR) 71-87 years]. Overall median survival from diagnosis was 205 days (IQR 60-532 days). One-year mortality was 62.3%. Patients were classified into two groups depending on the reason for a non-curable approach: patient-related (PR) or disease-related (DR). The difference in survival between PR (median 277 days, IQR 70-593) and DR (median 179 days, IQR 51-450) was 98 days (P = 0.023). Twenty-four patients were alive at the end of the study period; 19 out of 91 cases in PR (20.8%) and five out of 92 cases in DR (5.4%). Overall intervention rates were 11.9%, with higher rates in the DR group (P = 0.005). Disease stage was not associated with subsequent surgical intervention between the two groups (P = 0.392). CONCLUSION: Life expectancy for non-curatively managed patients within our unit was 6.8 months with one in nine patients requiring subsequent surgical admission for palliation. This information may be useful when counselling patients with incurable colorectal malignancy.