Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

BACKGROUND:Diabetic nephropathy is an important cause of end-stage renal disease,and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE:To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS:Thirty 8-week-old male SD rats were randomly assigned to healthy control group,model group and human umbilical cord mesenchymal stem cell group,with 10 rats in each group.Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy.Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time.1 week after the last injection,the histomorphological changes in the kidney and colon were observed under a light microscope.The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry.Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA.In addition,the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system.The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION:(1)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen,serum creatinine,24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats(all P<0.05).(2)The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats.(3)Compared with the healthy control group,the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced,while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells.(4)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats.(5)The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats.

Objective:To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis (AP).Methods:A prospective observational study was conducted, including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1, 2021 to November 30, 2022. Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period. Patients were classified into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group based on the 2012 Atlanta classification criteria. Patients with SAP were then divided into three subgroups of 1, 3, and 7 days based on the duration of hospitalization. Baseline data, such as gender, age, underlying disease, and probable etiology, was collected from all enrolled individuals. The enzyme-linked immunosorbent assay (ELISA) was employed to detect serum Claudin-5 levels in each cohort of enrollees. Data on additional serologic indicators, including hematocrit (HCT), albumin (Alb), serum Ca 2+, C-reactive protein (CRP), and procalcitonin (PCT) levels, were obtained via the in-hospital test query system in each group of patients with AP. The modified Marshall score (mMarshall), modified CT severity index (mCTSI) score, bedside severity index of severity in acute pancreatitis (BISAP) score, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) were recorded for each group of patients with AP. Differences in the above indicators between groups were analyzed and compared. Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each influencing factor on SAP. Ridge regression was used to screen for independent risk factors for SAP. Results:A total of 109 patients with AP were enrolled, comprising 66 in the MAP group, 15 in the MSAP group, and 28 in the SAP group. Additionally, 27 healthy volunteers were enrolled as the healthy control group. No statistically significant differences were observed in gender and age among the enrolled groups, and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition. As the disease progressed, serum Claudin-5 levels exhibited a notable increase across all AP patient groups, and they were all significantly higher than those in the healthy control group [ng/L: 888.58 (574.52, 1 141.59), 3 749.02 (2 784.93, 5 789.92), 4 667.81 (3 935.21, 7 315.66) vs. 291.13 (250.19, 314.75), all P < 0.05]. Subgroup analyses showed that as the disease duration prolonged, patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission, compared with those at 1 day post-admission [ng/L: 2 052.59 (1 089.43, 4 006.47) vs. 4 667.81 (3 935.21, 7 315.66), P < 0.05]. Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP, PCT, HCT, and mMarshall, mCTSI, and BISAP scores ( r values were 0.570, 0.525, 0.323, 0.774, 0.670, 0.652, all P < 0.001), and significantly negatively correlated with Alb ( r = -0.394, P < 0.001). A significant trend was observed in patients with AP, with an increase of HCT levels and a decrease of Alb levels as the disease progressed (both P < 0.05). An improvement of aforementioned phenomena was observed in patients with SAP following treatment, indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage. ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP, with the area under the ROC curve (AUC) of 0.948. When serum Claudin-5 levels ≥2 997 ng/L, the sensitivity for early screening for SAP was 100% and the specificity was 88.89%. Multifactorial ridge regression analysis showed that serum Claudin-5 level, PCT and APACHEⅡscore could be used as independent risk factors for early prediction of SAP (all P < 0.05). Conclusion:Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.

OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
Child ; Humans ; China ; Dwarfism ; Genetic Testing ; Heterozygote ; Syndrome

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

[摘 要] 目的：探讨幽门螺杆菌（Helicobacter pylori, Hp）感染对胃癌细胞共济失调毛细血管扩张突变（ataxia-telangiectasia mutated，ATM）基因表达的影响及其临床意义。方法：从TCGA数据库中获取胃癌相关RNAseq数据，比较ATM基因的表达差异，分析ATM表达与患者临床病理参数的相关性及预后价值，用Kaplan-Meier法进行生存分析，LinkedOmics数据库分析ATM相关基因，用R语言进行GO、KEGG富集分析。选用2019年3月至2019年12月贵州医科大学附属医院12例手术切除的胃癌及癌旁组织标本，以及胃癌细胞系AGS和BGC823，用感染复数40∶1的Hp GZ7菌感染细胞，用免疫组织化学染色法检测胃癌组织中ATM蛋白的表达，qPCR法检测胃癌组织和细胞中ATM mRNA的表达。结果：TCGA数据显示胃癌和Hp感染胃癌组织中ATM miRNA表达水平均显著高于癌旁组织（均P<0.01）；胃癌组织中ATM miRNA表达与患者的T分期、AJCC分期等病理参数呈正相关（均P<0.05），ATM高表达时生存率显著降低（P<0.05）。实验检测显示，胃癌组织标本中ATM蛋白的表达水平明显高于癌旁组织（P<0.01）；Hp感染胃癌细胞中ATM miRNA表达水平显著高于未感染胃癌细胞（P<0.01）。胃癌中ATM基因与NPAT等12 461个基因呈正相关（P<0.05），与MIF等7 764个基因呈负相关（P<0.05）。GO、KEGG富集分析显示，ATM富集到DNA修复复合体、癌症中的转录失调等信号通路。结论：ATM基因在胃癌组织中高表达，患者生存率随表达水平的增高而降低，其与患者的T分期、AJCC分期等病理参数相关，且Hp感染引起ATM表达水平升高可能是Hp引起胃癌的原因之一。

Objective:To study the new mechanism of Xuebijing injection improving the function of pulmonary vascular barrier from the perspective of claudin-5 protein.Methods:Acute lung injury (ALI) model was induced by hydrogen sulfide (H 2S) exposure. ① In vivo study: Sprague-Dawley (SD) rats were divided into control group, H 2S exposure group (exposure to 300×10 -6 H 2S for 3 hours), Xuebijing control group (Xuebijing injection 4 mL/kg, twice a day, for 3 days), and Xuebijing intervention group (H 2S exposure after pretreatment of Xuebijing injection) according to random number method, with 6 rats in each group. At different time points (0, 6, 12 and 24 hours) after the model was made successfully, the total protein content in plasma and bronchoalveolar lavage fluid (BALF) of rats were detected respectively, and the pulmonary permeability index (PPI) was calculated (PPI = protein content in BALF/protein content in plasma), lung dry/wet weight ratio (W/D) was detected, and claudin-5 mRNA expression in lung tissue was measured by real time-polymerase chain reaction. ② In vitro test: human pulmonary microvascular endothelial cells (HPMECs) were divided into blank control group, NaHS treatment group (co-incubated with 500 μmol/L NaHS for 12 hours), Xuebijing control group (2 g/L Xuebijing injection for 24 hours), and Xuebijing intervention group (2 g/L Xuebijing injection pre-treated for 24 hours, then co-incubated with 500 μmol/L NaHS for 12 hours). The HPMECs claudin-5 protein expression and monolayer permeability changes were measured at different co-incubation time (1, 3, 6, 12 and 24 hours) by Western Blot and fluoresceinsodium. Results:① In vivo study: compared with the control group, the lung W/D ratio increased significantly at 6 hours and peaked at 12 hours after H 2S exposure in rats (4.67±0.11 vs. 4.26±0.06, P < 0.01). The expression of claudin-5 mRNA in lung tissue was significantly decreased, which was 89% of control group 6 hours after exposure ( P < 0.01). The total protein content in BALF and PPI at 12 hours after exposure were significantly higher than those in the control group [total protein content (mg/L): 262.31±14.24 vs. 33.30±3.09, PPI: (11.72±0.57)×10 -3 vs. (1.21±0.08)×10 -3, both P < 0.01], while the results in Xuebijing intervention group were significantly decreased [total protein content (mg/L): 153.25±7.32 vs. 262.31±14.24, PPI: (5.79±0.23)×10 -3 vs. (11.72±0.57)×10 -3, both P < 0.01]. ② In vitro test: compared with the blank control group, after incubating HPMECs with NaHS, the permeability of monolayer endothelial cells gradually increased, reaching the highest level in 12 hours, about twice of that in the blank control group, while claudin-5 protein expression decreased to the lowest level at 12 hours (claudin-5/β-actin: 0.42±0.03 vs. 1.03±0.05, P < 0.01). After intervention with Xuebijing, the permeability of endothelial cells was significantly improved (fluorescence intensity of fluorescein sodium: 1.46±0.10 vs. 1.89±0.11, P < 0.01), and the decrease of claudin-5 protein was reduced (claudin-5/β-actin: 0.68±0.04 vs. 0.38±0.03, P < 0.01). Conclusion:Xuebijing injection may improve pulmonary vascular barrier function in ALI by upregulating claudin-5 expression.

Objective:To compare the therapeutic effects of nasal high-flow oxygen therapy (HFNC) and nasal canal oxygenation (NCO) during breaks off non-invasive ventilation (NIV) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore the feasibility of NIV combined with HFNC in the treatment of AECOPD.Methods:From August 2017 to July 2019, AECOPD patients with type Ⅱrespiratory failure (arterial blood gas pH <7.35, PaCO 2 > 50 mmHg) who were treated with NIV were randomly (random number) assigned to the HFNC group and NCO group at 1:1. The HFNC group received HFNC treatment during breaks from NIV and the NCO group received low-flow NCO during the NIV interval. The primary endpoint was the total respiratory support time. The secondary endpoints were endotracheal intubation, duration of NIV treatment and breaks from NIV, length of ICU stay, total length of hospital stay and so on. Results:Eighty-two patients were randomly assigned to the HFNC group and the NCO group. After secondary exclusion, 36 patients in the HFNC group and 37 patients in the NCO group were included in the analysis. The total respiratory support time in the HFNC group was significantly shorter than that in the NCO group [(74 ± 18) h vs. (93 ± 20) h, P = 0.042]. The total duration of NIV treatment in the HFNC group was significantly shorter than that in the NCO group [(36 ± 11) h vs. (51 ± 13) h, P=0.014]. There was no significant difference of the mean duration of single break from NIV between the two groups, but durations of break from NIV in the HFNC group were significantly longer than those in the NCO group since the third break from NIV ( P < 0.05). The intubation rates of the HFNC and NCO groups were 13.9% and 18.9%, respectively, with no significant difference ( P=0.562). The length of ICU stay in the HFNC group was (4.3 ± 1.7) days, which was shorter than that in the NCO group [(5.8 ± 2.1) days, P=0.045], but there was no significant difference in the total length of hospital stay between the two groups. Heart rate, respiratory rate, percutaneous carbon dioxide partial pressure and dyspnea score during the breaks from NIV in the NCO group were significantly higher than those in the HFNC group, and the comfort score was lower than that in the HFNC group ( P<0.05). Conclusion:For AECOPD patients receiving NIV, compared with NCO, HFNC during breaks from NIV can shorten respiratory support time and length of ICU stay, and improve carbon dioxide retention and dyspnea. HFNC is an ideal complement to NIV therapy in AECOPD patients.

OBJECTIVE：To study the mechanism of Periplaneta americana extract degreasing cream and CⅡ-3（shorted for “degreasing cream ”and“CⅡ-3”）reversing the multi-drug resistance of human HepG 2/ADM cells. METHODS ：MTT assay was used to investigate the toxicity effects of different concentrations of sorafenib （positive control ），degreasing cream and C Ⅱ-3 on HepG2/ADM cells ，then IC 20 was calculated. The experiment was divided into sensitivity drug ，drug-resistance group ，sorafenib group，degreasing cream group and C Ⅱ-3 group. HepG 2 cells were included in sensitivity group ，and HepG 2/ADM cells were included in the latter 4 groups. Sensitivity group and drug-resistance group were treated with routine medium ，and other 3 groups were treated with relevant medicine （IC20 as drug concentration ）. The content of ADM in HepG 2/ADM cells was determined by Laser scanning confocal microscopy. The expression of apoptosis-related protein as Bcl- 2 and Cleaved-Caspase- 9 p37 were detected by Western blotting assay. RT-qPCR and immunocytochemistry were adopted to detect mRNA and protein expressions that related to multidrug resistance [P-gp （expression produce of MDR1 gene），LRP，BCRP] and that related to enzyme-mediated multidrug resistance pathway （GST-π and Topo Ⅱ）. RESULTS ：The IC 20 of degreasing cream ，CⅡ-3 and sorafenib were （2.40±0.16）， （200.44±27.52），（18.00±1.82）μg/mL，respectively. Compared with sensitivity group ，the protein expressions of Bcl- 2，P-gp， LRP，BCRP and Topo Ⅱ，the mRNA expressions of MDR 1， LRP，BCRP and GST-π were increased significantly in drug resistance group （P＜0.05 or P＜0.01）. Compared with @qq.com drug-resistance group ，the mRNA and protein expression of MDR1 mRNA and LRP ，BCRP，GST-π were significantly decreased in degreasing cream group and C Ⅱ-3 group（P＜ 0.05 or P＜0.01）；the protein expression of Bcl- 2 and the mRNA expression of Topo Ⅱ were significantly decreased （P＜0.01）， while the protein expression level of Cleaved-Caspase- 9 p37 was significantly increased in C Ⅱ -3 group （P＜0.05）. CONCLUSIONS：Degreasing cream and C Ⅱ-3 can reverse multidrug resistance of HepG 2/ADM cells by reducing drug efflux ， promoting cell apoptosis ，reducing the mRNA and protein expression of multi-drug resistance gene as well as gene in enzyme-mediated multi-drug resistance pathway. The effect of C Ⅱ-3 is better than that of degreasing cream.

Objective To investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients. Methods The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group. Those who not received PPI were enrolled in the control group. A one-to-one propensity score matching (PSM) was performed to control for potential biases. The gender, age, underlying diseases, main diagnosis of ICU, drug use before ICU admission, sequential organ failure score (SOFA) at ICU admission, risk factors of stress ulcer (SU) and PPI usage were recorded. The end point was the incidence of gastrointestinal bleeding, hospital acquired pneumonia, Clostridium difficile infection and 30-day mortality. Kaplan-Meier survival curves were plotted, and survival analysis was performed using the log-rank test. Results 1 972 critical patients (788 in the SUP group and 1 184 in the control group) were enrolled, and each group enrolled 358 patients after PSM. Prior to PSM, compared with the control group, the SUP group had older patients, more underlying diseases, higher proportion of acute coronary syndrome (ACS), acute cerebrovascular disease, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and poisoning in main diagnosis of ICU, more serious illness, and more risk factors of SU, indicating that ICU physicians were more likely to prescribe SUP for these patients. The incidence of gastrointestinal bleeding in the SUP group was significantly lower than that in the control group [1.8% (14/788) vs. 3.7% (44/1 184), P < 0.05], while the incidence of hospital acquired pneumonia and 30-day mortality were significantly higher than those in the control group [6.6% (52/788) vs. 3.5% (42/1 184), 17.9% (141/788) vs. 13.1% (155/1 184), both P < 0.01]. There was no significant difference in the incidence of Clostridium difficile infection between the SUP group and the control group [2.9% (23/788) vs. 1.8% (21/1 184), P >0.05]. After the propensity scores for age, underlying diseases, severity of illness and SU risk factors were matched, there was no significant difference in the incidence of gastrointestinal bleeding or 30-day mortality between the SUP group and the control group [2.2% (8/358) vs. 3.4% (12/358), 15.9% (57/358) vs. 13.7% (49/358), both P > 0.05], but the incidence of hospital acquired pneumonia in the SUP group was still significantly higher than that in the control group [6.7% (24/358) vs. 3.1% (11/358), P < 0.05]. Kaplan-Meier survival curve analysis showed that the 30-day cumulative survival rate of the SUP group was significantly lower than that of the control group before the PSM (log-rank test: χ2 = 9.224, P = 0.002). There was no significant difference in the 30-day cumulative survival rate between the two groups after PSM (log-rank test: χ2 = 0.773, P = 0.379). Conclusion For critical patients, the use of PPI for SUP could not significantly reduce the incidence of gastrointestinal bleeding and mortality, but increase the risk of hospital acquired pneumonia.