Objective To investigate the relationship between circadian sleep-wake biorhythm and prognosis in patients with middle cerebral artery acute ischemic stroke.Methods A total of 71 patients with acute ischemic stroke of middle cerebral artery were selected as the case group,and 67 patients without acute ischemic stroke and cerebrovascular stenosis were selected as the control group.According to the modified Rankin score at discharge,patients with acute ischemic stroke were subdivided into the good prognosis group(53 cases)and the poor prognosis group(18 cases).General clinical data of patients were collected,and differences of circadian rhythm,daytime sleep-wake rhythm,nighttime sleep-wake rhythm and circadian sleep-wake rhythm indexes were analyzed and compared between the two groups.Multivariate Logistic stepwise regression analysis was used to analyze prognostic factors of acute ischemic stroke in middle cerebral artery.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of relevant variables.Results Age,male ratio,hypertension,diabetes,hyperlipidemia,smoking and drinking history were significantly higher in the case group than those in the control group.Daytime stability(IS)in the case group was lower than that in the control group(P＜0.05).Daytime total sleep time,wake time after falling asleep,light sleep period,deep sleep period,non-rapid eye movement(NREM)sleep period,rapid eye movement(REM)sleep period and the proportion of deep sleep period,the proportion of REM sleep period were higher in the case group than those of the control group,while the REM sleep latency and the proportion of light sleep period were lower than those of the control group(P＜0.05).The total sleep time,wake time,light sleep period,NREM sleep period and REM sleep period were higher in the case group than those of control group,while the proportion of sleep latency and REM sleep period were lower than those of the control group(P＜0.05).The proportion of increased circadian sleep,increased daytime sleep and low sleep efficiency at night were higher in the case group than those of the control group(P＜0.05).Logistic stepwise regression analysis showed that daytime REM sleep was a prognistic factor in middle cerebral artery acute ischemic stroke.During daytime REM sleep,the area under ROC curve(AUC)was 0.705,the sensitivity was 0.811 and the specificity was 0.611.Conclusion After acute ischemic stroke of middle cerebral artery,the circadian sleep-wake rhythm is unbalanced,which is manifested as poor daytime stability,increased daytime sleep,increased circadian sleep and low sleep efficiency at night.Daytime REM sleep has predictive value for prognosis of acute ischemic stroke of middle cerebral artery.

Objective To evaluate the efficacy and safety of single-used flexible ureteroscope lithotripsy(FURL)in the treatment of 2.0-3.0 cm non-lower-pole renal stones in elderly patients.Methods A total of 78 elderly patients with non-lower-pole renal stones measuring 2.0-3.0 cm admitted to our hospital were included in this study.Based on the surgical procedure,the patients were divided into the FURL group(42 cases of FURL with holmium laser lithotripsy)and the MPCNL group[36 cases of minimally invasive percutaneous nephrolithotomy(MPCNL)with holmium caser lithotripsy].Various parameters including operation time,stone fragmentation time,postoperative decrease of hemoglobin(Hb)level,postoperative Visual Analog Scale(VAS)for pain,hospitalization duration,stone-free rate(SFR)at 1 week and 4 weeks after surgery,secondary surgery rate,and incidence of complications were compared between the two groups.Results All the patients successfully underwent surgery.The decrease of Hb in the FURL group was(4.4±1.6)g/L,significantly lower than that in the MPCNL group[(24.7±4.6)g/L,t=-25.342,P=0.000].The postoperative VAS scores of the FURL group was(1.6±0.4)points,significantly lower than that of the MPCNL group[(5.6±0.9)points,t=-25.642,P=0.000].The stone fragmentation time in the FURL group was(82.5±10.2)min,significantly longer than that in the MPCNL group[(53.8±8.4)min,t=13.437,P=0.000].The operation time in the FURL group was(98.3±12.5)min,and there was no statistically significant difference compared to the MPCNL group[(96.7±11.8)min,t=0.555,P=0581].The hospitalization time in the FURL group was(3.5±1.5)d,significantly shorter than that in the MPCNL group[(8.6±1.7)d,t=-13.947,P=0.000].The incidence of complications in the FURL group was 26.2％(11/42),and there was no significant difference compared to the MPCNL group[27.8％(10/36),x2=0.025,P=0.875].The proportion of secondary treatment in the FURL group was 19.0％(8/42),and there was no significant difference compared to the MPCNL group[11.1％(4/36),x2=0.938,P=0.333].At 1 week after surgery,the SFR of the FURL group was 54.8％(23/42),significantly lower than that of the MPCNL group[86.1％(31/36),x2=8.943,P=0.003].At 4 weeks after surgery,there was no significant difference in SFR between the FURL group[90.5％(38/42)]and the MPCNL group[91.7％(33/36),x2=0.000,P=1.000].Conclusions Single-used flexible ureteroscope lithotripsy is highly effective in the treatment of non-lower-pole renal stones measuring 2.0-3.0 cm in elderly patients.It offers advantages such as minimal invasion,rapid recovery,minimal bleeding,low incidence of complications,and shorter hospitalization duration,which is worthy of promotion.

Transjugular intrahepatic portosystemic shunt （TIPS） has been recommended as a treatment method for cirrhotic portal hypertension in domestic and foreign guidelines， but there is still uncertainty in its therapeutic efficacy. More and more studies have shown that TIPS combined with collateral vessel embolization （TIPS+E） has certain advantages in the treatment of gastroesophageal variceal bleeding in liver cirrhosis. This article reviews the major studies on TIPS+E in China and globally， summarizes related recommendations in guidelines and the current status of clinical application， and proposes the issues that need to be solved， such as indication， hemodynamic criteria， and selection of materials for embolization， and large－sample multicenter randomized controlled trials are needed for further clarification.

Objective:To observe whether α1 adrenergic receptor (α1AR) blocker can reduce and antagonize portal hypertension caused by α1AR activation in rats, and to provide a new approach for the clinical treatment of portal hypertension.Methods:Phenylephrine was chosen as α1AR agonist, and alfuzosin was used as α1AR blocker. The route of administration was portal vein injection, and the pressure was measured by trans-portal vein puncture. According to random number table, 32 male Sprague-Dawley rats were divided into 4 groups: control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group. The portal venous pressure (PVP) was measured in all rats before administration. The rats in the control group were injected with 0.9% sodium chloride solution (1 L/g), and the rats in portal hypertension model group were injected with phenylephrine(1.5 μg/g), and the PVP of the above two groups was measured again at 5 and 10 min after injection. The rats in alfuzosin treatment group were injected with phenylephrine(1.5 μg/g), PVP was measured again at 5 min after administration, and then the rats were given alfuzosin(0.9 μg/g), PVP was measured again at 5 min after administration. The rats in alfuzosin prevention group were injected with alfuzosin(0.9 μg/g), PVP was measured at 1 min after administration, and then the rats were given phenylephrine(1.5 μg/g), PVP was measured again at 1, 5 and 10 min after phenylephrine injection respectively. One way analysis of variance and Dunnett- t test were used for statistical analysis. Results:The portal vein puncture was successfully performed in 4, 6, 8 and 5 rats in the control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group, respectively. The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was (18.045±7.636) and (15.515±5.440) mmHg (1 mmHg = 0.133 kPa), respectively, which were both higher than that before administration ((8.452±2.830) mmHg), and the differences were statistically significant ( t=2.89 and 2.82, both P<0.05). At 5 min after alfuzosin injection, the PVP of rats in the alfuzosin treatment group was (10.088±3.743) mmHg, which was lower than that of rats at 5 min after phenylephrine injection ((16.146±4.324) mmHg) and that of portal hypertension model group at 10 min after phenylephrine injection, and the differences were statistically significant ( t=3.00 and 2.22, both P<0.05). There were no significant differences in PVP in the alfuzosin prevention group before administration, at 1 min after injection of alfuzosin, and at 1, 5 and 10 min after injection of phenylephrine (all P > 0.05). Conclusions:α1AR is an important factor involved in the regulation of PVP, and its blockers can reduce and antagonize the portal hypertension caused by α1AR activation, which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.

Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.

The cyclic dinucleotide c-di-GMP is known as an important second messenger in bacteria, which controls various important cellular processes, such as cell differentiation, biofilm formation and virulence factors production. It is extremely vital for the development of new antibacterial agents by virtue of blocking c-di-GMP signal conduction. Current research indicates that there are three potential targets for discovering new antibacterial agents based on c-di-GMP regulated signal pathway, which are c-di-GMP synthases, c-di-GMP degrading enzymes and c-di-GMP receptors. Herein, we review small molecules that have been developed to inhibit c-di-GMP related enzymes and indicate perspectives of c-di-GMP inhibitors.

Biofilm is a bacterial lifestyle ubiquitously in natural environments. Bacterial biofilm leads to drug resistance, a main reason why many infectious diseases are difficult to control. Due to the prominent points of biofilms implicated in infectious disease and the spread of multi-drug resistance, it is urgent to discover new antibacterial agents that can regulate biofilm formation and development. This review introduces chemical agents that could modulate bacterial biofilm formation and development.

Biofilm is prevalent in various ecological niches, in which microbial cells interconnect with each other through extracellular polymeric substances including polysaccharides, extracellular DNA, and proteins. When living in biofilms, the microbial cells employ small signalling chemicals as their "language" to communicate mutually, and exhibit remarkable differences in physiology compared to those living in planktonic state. It has been proven that the development of biofilm is subject to the regulation of c-di-GMP, an important second messenger found in prokaryotes. Given its important roles of biofilms in microbial infection, industry application, plant-microbe interactions and environmental pollustion, biofilm is one of frontier research areas in microbiology. This special issue of "Biofilm and c-di-GMP" systematically reviews the current progresses in the multiple research frontiers, including biotechnology, infectious diseases, environmental microbiology and plant pathology, with special focus on the methods and techniques in biofilm research. We hope that the issue will boost the interest of students and young scientists in this exciting area of microbiology.

Objective To explore the effects of miRNA-218 on renal cell carcinoma of nude mice in vivo.Methods The pcDNA3.1-miR-218 and its control negative plasmids were stably transfected into renal cell carcinoma cell line A498 and 769-P.These cells were inoculated into nude mice in different groups to observe the changes of body and tumor and to detect the expression of miR-218 in the tissues of nude mice.Results In the A498 cells + pcDNA3.1-miR-218 transfected group,the weight loss of tumor bearing nude mice after 25 days was lower than that in the control group,and the tumor volume was smaller than that in the control group after 10 days (P ＜ 0.05).In the 769-P cells + pcDNA3.1-miR-218 transfected group,the weight loss of tumor bearing nude mice was lower than that in the control group after 19 days,and the tumor volume was smaller than that in control group after 10 days (P ＜ 0.05).The expression of miRNA-218 in bearing nude mice with A498 cells or 769-P cells transfected by miRNA-218 was significantly higher than that in the control group,and the difference was statistically significant (P ＜ 0.05).Conclusion Up-regulation of miRNA-218 expression can inhibit the growth of renal cell carcinoma of nude mice in vivo.

Pseudomonas aeruginosa causes severe and persistent infections in immune compromised individuals and cystic fibrosis sufferers. The infection is hard to eradicate as P. aeruginosa has developed strong resistance to most conventional antibiotics. The problem is further compounded by the ability of the pathogen to form biofilm matrix, which provides bacterial cells a protected environment withstanding various stresses including antibiotics. Quorum sensing (QS), a cell density-based intercellular communication system, which plays a key role in regulation of the bacterial virulence and biofilm formation, could be a promising target for developing new strategies against P. aeruginosa infection. The QS network of P. aeruginosa is organized in a multi-layered hierarchy consisting of at least four interconnected signaling mechanisms. Evidence is accumulating that the QS regulatory network not only responds to bacterial population changes but also could react to environmental stress cues. This plasticity should be taken into consideration during exploration and development of anti-QS therapeutics.
4-Butyrolactone ; analogs & derivatives ; chemistry ; metabolism ; Bacterial Proteins ; metabolism ; Iron ; chemistry ; metabolism ; Pseudomonas aeruginosa ; physiology ; Quorum Sensing ; physiology ; Signal Transduction ; Trans-Activators ; metabolism ; Virulence