Isoquercitrin attenuates the osteoclast-mediated bone loss in rheumatoid arthritis via the Nrf2/ROS/NF-κB pathway.

An excess of osteoclastogenesis significantly contributes to the development of rheumatoid arthritis (RA). Activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS)-to-NF-κB signaling cascade are important mechanisms regulating osteoclastogenesis; however, whether Nrf2 is involved in RANKL-induced NF-κB activation is controversial. Isoquercitrin, a natural flavonoid compound, has been shown to have Nrf2-dependent antioxidant effects inprevious studies. We sought to verify whether isoquercitrin could modulate RANKL-induced NF-κB activation by activating Nrf2, thereby affecting osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin ring staining and resorption pit assay suggested that isoquercitrin significantly inhibited osteoclastogenesis and osteolytic function. Mitosox staining showed that RANKL-induced ROS generation was significantly inhibited by isoquercitrin from day 3 of the osteoclast differentiation cycle. Quantitative real-time PCR, Western blot, and immunofluorescence indicated that isoquercitrin activated the Nrf2 signaling pathway and inhibited NF-κB expression. And when we used the Nrf2-specific inhibitor ML385, the inhibition of NF-κB by isoquercitrin disappeared. Moreover, we found that Nrf2 is not uninvolved in RANKL-induced NF-κB activation and may be related to the timing of ROS regulation. When we limited isoquercitrin administration to 2 days, Nrf2 remained activated and the inhibition of NF-κB disappeared. In vivo experiments suggested that isoquercitrin attenuated RA modeling-induced bone loss. Overall, isoquercitrin-activated Nrf2 blocked the RANKL-induced ROS-to-NF-κB signaling cascade response, thereby inhibiting osteoclastogenesis and bone loss. These findings provide new ideas for the treatment of RA.

Case report: Transcatheter arterial embolization in a newborn with cervical rapidly involuting congenital hemangioma and Kasabach-Merritt phenomenon.

Congenital hemangiomas (CHs) are rare vascular tumors and do not exhibit progressive postnatal growth. The incidence is less than 3% of all hemangiomas. Most CHs have a favorable prognosis; however, the Kasabach-Merritt phenomenon (KMP) is a rare but life-threatening complication in CHs that requires aggressive treatment. Medical treatments with corticosteroids and interferon have been suggested. Surgical resection can be considered for the treatment of complicated CHs in medically resistant lesions. Vascular embolization could be an alternative method if surgery is not considered feasible. Herein, we report a case of a 9-day-old newborn who underwent arterial embolization for a CH with KMP, combined with sirolimus treatment, and the outcome was favorable. The hemangioma completely regressed by 3 months and rapidly involuting congenital hemangioma (RICH) was diagnosed. Our successful experience with treating RICH associated with KMP revealed that RICH can have potentially serious complications although they usually resolve rapidly after birth without treatment. Surgical resection is considered to be the standard method for the treatment of medically resistant vascular tumors, but it is difficult to perform during the active phase of KMP due to acute bleeding and severe coagulopathy. Arterial embolization is feasible and can be used as an alternative to surgical resection, even in small babies.

[Construction and evaluation of a gradient stress model of PC12 cells induced by corticosterone].

Objective: A gradient stress model of PC12 cells induced by corticosterone was established to provide a basis for the evaluation and regulation of cell stress. Methods: The effect of corticosterone on cell viability was observed by measuring PC12 cell viability at different concentrations of corticosterone (0~1 000 µmol/L) after different intervention times (8~48 h) to screen the cell models for optimal intervention conditions. Key stress indicators (MDA, SOD, NADH, LDH) were measured spectrophotometrically and microscopically to evaluate the models. Results: When the concentration of corticosterone was below 200 µmol/L and the intervention time was 12 h, the cell viability was below half inactivation rate, which could reduce the confounding factors due to the decrease of cell viability in each group. Compared with the blank control group, corticosterone increased the levels of MDA, NADH and LDH,and decreased the levels of SOD in the model group in a concentration-dependent manner (P＜0.01), which was consistent with the construction of the gradient stress model. Conclusion: A gradient stress injury model of PC12 cells was successfully established, with intervention concentrations of 0 µmol/L, 25 µmol/L, 50 µmol/L, 100 µmol/L, 150 µmol/L and 200 µmol/L corticosterone at an intervention time of 12 h. The degree of stress injury of the cell model was increased gradually, which could be used as a basis and object for conducting cell stress injury assessment and regulation experiments.

Baseline Serum Estradiol Level Is Associated with Acute Kidney Injury in Patients with Moderately Severe and Severe Acute Pancreatitis.

Background: Sexual dimorphism with critical diseases has been documented. However, the role of serum sex hormones for the presence of acute kidney injury (AKI) in moderately or severe acute pancreatitis (MSAP and SAP) patients remains controversial. Here we set out to evaluate whether early (first 48 h) serum estradiol level is associated with AKI in patients with MSAP and SAP. Patients and Methods. We retrospectively collected data from patients with preliminary diagnosis of MSAP and SAP from the Affiliated Hospital of Yangzhou University between January 2014 and June 2018. Serum sex hormones were extracted for further assessment within first 48 h following admission. Logistic regression analysis and the receiving operating characteristic (ROC) curve were applied to evaluate the association and correlation between serum sex hormones and AKI. Results: Data from a total of 122 patients with MSAP or SAP were enrolled in this study. There were no differences in the incidence of AKI between males and females. However, comparing with patients without AKI, those with AKI saw higher estradiol level (p ≤ 0.01) and slight higher progesterone level (p = 0.014) but similar testosterone level (p = 0.668). Interestingly, during both the manual selection and the stepwise backward logistic regression analysis, serum estradiol level was independently associated with AKI in patients with MSAP and SAP (OR 4.699, CI 1.783-12.386, and p = 0.002). Additionally, area under the curve of ROC (AUCROC) showed that serum estradiol level was a proper predictor for AKI (area under the curve 0.875). Specifically, the serum estradiol level of 223.15 pg/mL demonstrated a 92.3% sensitive and a 79.3% specificity in predicting AKI of MSAP and SAP patients, respectively. Conclusions: High baseline serum estradiol level appears to be an independent risk factor for AKI in patients with MSAP and SAP. It also tends to be an appropriate indicator for AKI.

The causal relationship between allergic diseases and heart failure: Evidence from Mendelian randomization study.

BACKGROUND: Emerging evidence shows allergic diseases, such as atopic dermatitis and asthma, are risk factors of heart failure. However, the causal relationship between allergic diseases and heart failure is not clear. METHODS: We performed a two-sample Mendelian randomization analysis between allergic diseases and heart failure using summary statistics of genome-wide association studies from large GWAS consortia, with total sample size of 1.2 million. Independent instrumental variables for asthma and atopic dermatitis (P<1×10-5) were used as the exposure. We applied five models for the Mendelian randomization analysis. Finally, we performed the sensitivity analyses to assess the robustness of the results. RESULTS: We have identified 55 independent single nucleotide polymorphisms (SNPs) for asthma 54 independent SNPs for atopic dermatitis as our instrumental variables. The inverse variance-weighted (IVW) analysis showed asthma was significantly associated with increased risk of heart failure (ORIVW = 1.04, 95% CI, 1.01-1.07, P = 0.03). The Mendelian randomization analysis using the other four models also showed consistent results with the IVW analysis. Similarly, atopic dermatitis was also significantly associated with an increased risk of heart failure (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.01), consistent with the other four models. The sensitivity analysis showed no evidence of horizontal pleiotropy or results were driven by single SNPs. CONCLUSION: Our study identified asthma and atopic dermatitis as a causal risk factor for heart failure and suggest inflammatory pathogenesis as a key factor contributing to the underlying mechanism. These findings emphasize the importance of asthma and allergy control in the prevention and management of heart failure.

Bromodomains regulate dynamic targeting of the PBAF chromatin-remodeling complex to chromatin hubs.

Chromatin remodelers actively target arrays of acetylated nucleosomes at select enhancers and promoters to facilitate or shut down the repeated recruitment of RNA polymerase II during transcriptional bursting. It is poorly understood how chromatin remodelers such as PBAF dynamically target different chromatin states inside a live cell. Our live-cell single-molecule fluorescence microscopy study reveals chromatin hubs throughout the nucleus where PBAF rapidly cycles on and off the genome. Deletion of PBAF's bromodomains impairs targeting and stable engagement of chromatin in hubs. Dual color imaging reveals that PBAF targets both euchromatic and heterochromatic hubs with distinct genome-binding kinetic profiles that mimic chromatin stability. Removal of PBAF's bromodomains stabilizes H3.3 binding within chromatin, indicating that bromodomains may play a direct role in remodeling of the nucleosome. Our data suggests that PBAF's dynamic bromodomain-mediated engagement of a nucleosome may reflect the chromatin-remodeling potential of differentially bound chromatin states.

[Resveratrol attenuates cardiac function impairment in plateau hypobaric hypoxia rats].

Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly (P＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group (P＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly (P＜0.05), while the platelet concentration was decreased significantly(P＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly (P＜0.05) and platelet concentration was increased significantly(P＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group (P＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group (P＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness (P＜0.05) and a significant decrease in ejection fraction and cardiac output (P＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function (P＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group (P＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group (P＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly (P＜0.05) and the MDA level was increased significantly (P＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly (P＜0.05) and the MDA level was decreased significantly(P＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.

Isolated partial anomalous origin of a branch pulmonary artery from the descending aorta.

The condition of partial anomalous origin of a branch pulmonary artery from the descending aorta could be found in several diseases and should be carefully differentiated. We report an unusual case of anomalous systemic arterial supply to normal basal segments of the left lower lung and another case of intralobar pulmonary sequestration. These two cases were treated successfully by transarterial embolisation using the Amplatzer Vascular Plug. We also set up a diagnostic algorithm to differentiate these diseases from anomalous systemic arterial supply to the pulmonary region. It is possible to make the correct diagnosis using the step-by-step diagnostic algorithm and careful interpretation of chest computed tomography angiography.

Ultrasonographic measurements of femoral vessel diameter in neonates weighing less than 2.5 kg.

BACKGROUND: Cannulation in low birth weight (LBW) neonates using larger sheaths could increase the risk of vascular injury. This study investigated the relationship between body weight (BW) and diameter of femoral vessels in LBW neonates and whether BW can be used to predict femoral vessel diameter. METHODS: The cohort included 100 neonates weighing < 2.5 kg (.57-2.42 kg) with a gestational age of 24-39 weeks. Vascular ultrasonography was used to measure diameters of the bilateral femoral arteries (FA) and veins (FV). The cohort was divided into four groups according to weight: group-A, 2-2.49 kg (n = 28); group-B, 1.5-1.99 kg (n = 38); group-C, 1-1.49 kg (n = 21); and group-D, < 1 kg (n = 13); or according to BSA: group-A, BSA > .16 m2 (n = 25); group-B, .13-.16 m2 (n = 40); group-C, .1-.13 m2 (n = 22); and group-D, < .1 m2 (n = 13). RESULTS: The median vessel diameters (mm) in groups A-D according to weight were FA, 1.96, 1.86, 1.78, and 1.53, and FV, 2.30, 2.28, 2.13, and 1.87, respectively. The median vessel diameters (mm) in groups A-D according to BSA were FA, 1.96, 1.86, 1.76, and 1.53, and FV, 2.30, 2.28, 2.05, and 1.87, respectively. There were positive correlations between BW and femoral vessel diameter (correlation coefficient: .56 and .55 between BW and FA and FV, respectively) (p < 0.001), and between BSA and femoral vessel diameter (correlation coefficient: .56 and .55 between BSA and FA and FV, respectively) (p < 0.001). CONCLUSIONS: BW is a predictor of femoral vessel diameter in LBW newborns. This finding may help to avoid using larger sheath in smaller vessels.

Initial fluid resuscitation (30 mL/kg) in patients with septic shock: More or less?

OBJECTIVES: The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock. METHODS: This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes. MEASUREMENTS AND MAIN RESULTS: A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P < 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P < 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P < 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016). CONCLUSION: In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

The Construction and Comprehensive Analysis of Inflammation-Related ceRNA Networks and Tissue-Infiltrating Immune Cells in Ulcerative Progression.

Ulcerative colitis (UC) is a common disease with great variability in severity, with a high recurrence rate and heavy disease burden. In recent years, the different biological functions of competing endogenous RNA (ceRNA) networks of long noncoding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns, the ceRNA network of ulcerative colitis (UC) may have potential research value, and these expressed noncoding RNAs may be involved in the molecular basis of inflammation recurrence and progression. This study analyzed 490 colon samples associated with UC from 4 gene expression microarrays from the GEO database and identified gene modules by weighted correlation network analysis (WGCNA). CIBERSORT detected tissue-infiltrating leukocyte profiling by deconvolution of microarray data. LncBase and multiMIR were used to identify lncRNA-miRNA-mRNA interaction. We constructed a ceRNA network which includes 4 lncRNAs (SH3BP5-AS1, MIR4435-2HG, ENTPD1-AS1, and AC007750.1), 5 miRNAs (miR-141-3p, miR-191-5p, miR-192-5p, miR-194-5p, and miR196-5p), and 52 mRNAs. Those genes are involved in interleukin family signals, neutrophil degranulation, adaptive immunity, and cell adhesion pathways. lncRNA MIR4435-2HG is a variable in the decision tree for moderate-to-severe UC diagnostic prediction. Our work identifies potential regulated inflammation-related lncRNA-miRNA-mRNA regulatory axes. The regulatory axes are dysregulated during the deterioration of UC, suggesting that it is a risk factor for UC progression.

Structure of the p53/RNA polymerase II assembly.

The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53's DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II's jaw that contacts downstream DNA. These findings suggest that p53's functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.

Elevated PCT at ICU discharge predicts poor prognosis in patients with severe traumatic brain injury: a retrospective cohort study.

PURPOSE: Disease severity and inflammatory response status are closely related to a poor prognosis and must be assessed in patients with severe traumatic brain injury (STBI) before intensive care unit (ICU) discharge. Whether elevated serum procalcitonin (PCT) levels can predict a poor prognosis in STBI patients before ICU discharge is unclear. METHODS: This retrospective observational cohort study enrolled 199 STBI patients who were in the ICU for at least 48 hours and survived after discharge. Based on serum PCT levels at discharge, patients were divided into the high-PCT group (PCT ≥ 0.25 ng/mL) and the low-PCT group (PCT < 0.25 ng/mL). We assessed the relationship between serum PCT levels and a poor prognosis. RESULTS: The high-PCT group had a higher rate of adverse outcomes compared with the low-PCT group. Multivariate logistic regression analysis showed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, white blood cell (WBC) count, C-reactive protein (CRP) level, and PCT level at discharge were significantly associated with adverse outcomes. CONCLUSIONS: Elevated PCT levels at ICU discharge were associated with a poor prognosis in STBI patients. The serum PCT level as a single indicator has limited value for clinical decision-making.

Chlorine disinfection promotes the exchange of antibiotic resistance genes across bacterial genera by natural transformation.

Chlorine disinfection to drinking water plays an important role in preventing and controlling waterborne disease outbreaks globally. Nevertheless, little is known about why it enriches the antibiotic resistance genes (ARGs) in bacteria after chlorination. Here, ARGs released from killed antibiotic-resistant bacteria (ARB), and culturable chlorine-injured bacteria produced in the chlorination process as the recipient, were investigated to determine their contribution to the horizontal transfer of ARGs during disinfection treatment. We discovered Escherichia coli, Salmonella aberdeen, Pseudomonas aeruginosa and Enterococcus faecalis showed diverse resistance to sodium hypochlorite, and transferable RP4 could be released from killed sensitive donor consistently. Meanwhile, the survival of chlorine-tolerant injured bacteria with enhanced cell membrane permeabilisation and a strong oxidative stress-response demonstrated that a physiologically competent cell could be transferred by RP4 with an improved transformation frequency of up to 550 times compared with the corresponding untreated bacteria. Furthermore, the water quality factors involving chemical oxygen demand (CODMn), ammonium nitrogen and metal ions (Ca2+ and K+) could significantly promote above transformation frequency of released RP4 into injured E. faecalis. Our findings demonstrated that the chlorination process promoted the horizontal transfer of plasmids by natural transformation, which resulted in the exchange of ARGs across bacterial genera and the emergence of new ARB, as well as the transfer of chlorine-injured opportunistic pathogen from non-ARB to ARB. Considering that the transfer elements were quite resistant to degradation through disinfection, this situation poses a potential risk to public health.

[Risk factors for minimally invasive surfactant administration failure in preterm infants with respiratory distress syndrome].

OBJECTIVE: To identify risk factors for minimally invasive surfactant administration (MISA) failure in the treatment of preterm infants with respiratory distress syndrome (RDS) and the influence of MISA failure on neonatal outcome. METHODS: A retrospective analysis was performed for the clinical data of 148 preterm infants with a gestational age of ≤32 weeks and a clinical diagnosis of RDS, who were admitted to the neonatal intensive care unit of eight tertiary hospitals in Beijing, Tianjin and Hebei Province from July 1, 2017 to December 31, 2018 and were treated with MISA (bovine pulmonary surfactant, PS). According to whether MISA failure (defined as the need for mechanical ventilation within 72 hours after MISA) was observed, the infants were divided into two groups: MISA failure group (n=16) and MISA success (n=132). A logistic regression analysis was used to investigate the risk factors for MISA failure and its influence on neonatal outcome. RESULTS: The MISA failure rate was 10.8% (16/148). The logistic regression analysis showed that a high incidence rate of grade >II RDS before PS administration, low mean arterial pressure and high pulse pressure before administration, a low dose of initial PS administration, and long injection time and operation time were the risk factors for MISA failure (OR=5.983, 1.210, 1.183, 1.055, 1.036, and 1.058 respectively, P<0.05). After the control for the above risk factors, the logistic regression analysis showed that the MISA failure group had a significantly higher incidence rate of bronchopulmonary dysplasia (BPD) (OR=8.537, P<0.05). CONCLUSIONS: A high grade of RDS, a low mean arterial pressure, and a high pulse pressure before administration are independent risk factors for MISA failure, and a low dose of initial PS administration, a long injection time, and a long operation time may increase the risk of MISA failure. MISA failure may increase the incidence rate of BPD in preterm infants.

Endoscopic submucosal dissection for localised gastric amyloidosis mimicking malignancy / Disección submucosa endoscópica para la amiloidosis localizada gástrica que simula una malignidad

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Analysis of small bowel angioectasia in asymptomatic individuals depending on patients' age and gender.

Objectives: Small bowel angioectasia (SBA) plays an important role in the etiologies of obscure gastrointestinal haemorrhage. But the exact prevalence of the disease is unknown, especially in asymptomatic populations. Therefore, we aimed to evaluate the prevalence of asymptomatic angioectasia in the small bowel (SB) with magnetically controlled capsule gastroscopy (MCCG).Methods: We retrospectively collected a multicentre clinical data of 508 asymptomatic patients who underwent MCCG from June 2018 to May 2019. Bowel cleanliness was rated as four grades according to the criteria, and the excellent or good preparation was classified as the adequate group. The detection rates of small bowel lesions were analysed according to the ages, genders and bowel preparations.Results: A total of 508 individuals have completed the examination. There were 316 men and 192 women with an average age of 44.5 years old. The prevalence of SBA was 11.8% (95% CI: 9.0-14.6%). 70.0% of them were over 40 years old and 73.3% were male although there was no obvious disparity found in age and gender for the SBA. Most findings were located in the proximal small bowel (jejunum). The incidence of small bowel lesions was not related to bowel preparations (p > .05).Conclusions: SBA is not uncommon in asymptomatic individuals. Age and gender may be risk factors for bleeding of angioectasia in the small bowel, but they seem to have little to do with the occurrence of it. MCCG showed no difference in ages, genders or bowel preparations of small bowel lesions among our study population.

[The effects of Sestrin2 on apoptosis of heat-exposed lung epithelial cells and its mechanism].

OBJECTIVE: To investigate the protective effects of Sestrin2 protein on lung epithelial Beas-2B cells in the heat-exposure environment and its mechanism. METHODS: Lung epithelial Beas-2B cells were cultured at 37℃, 39℃, 40℃ and 41℃ respectively. Cells were harvested at different times (0, 3, 6 and 12 h) after pancreatin digestion. The expressions of Sestrin2, superoxide dismutase(SOD), reactive oxygen species(ROS), cell mitochondrial membrane potential and apoptosis rate of cells were detected by Western blot, fluorescence spectrophotometer and flow cytometry, respectively. Gene expression sequence was cloned into high expression plasmid pcDNA3.1+. Beas-2B cells were transfected by Lipfectamine 2000 to construct Sestrin2 and SOD high expression cells. The changes of mitochondrial membrane potential and cell apoptosis were observed in the Sestrin2 and SOD high expression cells. RESULTS: With the increase of temperature, the expression level of Sestrin2 protein in heat treatment group was decreased compared with the control group. When Beas-2B cells were exposed to 41℃, the ROS level was increased, mitochondrial membrane potential was decreased significantly and apoptosis rate was increased at different time points. After high expression of Sestrin2 and SOD in the Beas-2B cells, the expression level of ROS was decreased and the change tendency of mitochondrial membrane potential was decreased, and the apoptosis rate was reduced at 41℃ exposure. CONCLUSION: Sestrin2 can alleviate the apoptosis of lung epithelial cells induced by heat exposure through mitochondrial membrane potential and SOD, which has protective effect on lung epithelial Beas-2B cells.

Chlorine injury enhances antibiotic resistance in Pseudomonas aeruginosa through over expression of drug efflux pumps.

Adaption to adverse environments plays an important role in bacterial survival and is receiving increasing globe attention now. Here, cultivable chlorine-injured Pseudomonas aeruginosa, produced on the chlorination process, was investigated about their resistance to antibiotics. Then, global transcriptional analyses, quantitative PCR (qPCR) validation and antioxidant enzymes measurement were performed to explore the underlying mechanisms. The results showed that chlorine injury enhanced antibiotic resistance in P. aeruginosa and cultivable chlorine-injured P. aeruginosa exposed to 4 mg/L sodium hypochlorite (half of the lethal dose) improved antibiotic resistance against ceftazidime, chloramphenicol and ampicillin by 1.4-5.6 fold. This increase in antibiotic resistance was not hereditable and over expression of the MexEF-OprN efflux pump resulting from oxidative stress contributed to it. These results demonstrate temporal physiological persistence to antibiotics in cultivable chlorine-injured pathogens, suggesting their survival from adverse environments with antibiotic exposure and thereby posing lasting hazards to human health.