Effect of metformin on sepsis-associated acute lung injury and gut microbiota in aged rats with sepsis.

Background: Recent studies reported the association between the changes in gut microbiota and sepsis, but there is unclear for the gut microbes on aged sepsis is associated acute lung injury (SALI), and metformin treatment for the change in gut microbiota. This study aimed to investigate the effect of metformin on gut microbiota and SALI in aged rats with sepsis. It also explored the therapeutic mechanism and the effect of metformin on aged rats with SALI. Methods: Aged 20-21 months SD rats were categorized into three groups: sham-operated rats (AgS group), rats with cecal ligation and puncture (CLP)-induced sepsis (AgCLP group), and rats treated with metformin (100 mg/kg) orally 1 h after CLP treatment (AgMET group). We collected feces from rats and analyzed them by 16S rRNA sequencing. Further, the lung samples were collected for histological analysis and quantitative real-time PCR (qPCR) assay and so on. Results: This study showed that some pathological changes occurring in the lungs of aged rats, such as hemorrhage, edema, and inflammation, improved after metformin treatment; the number of hepatocyte death increased in the AgCLP group, and decreased in the AgMET group. Moreover, metformin relieved SALI inflammation and damage. Importantly, the gut microbiota composition among the three groups in aged SALI rats was different. In particular, the proportion of E. coli and K. pneumoniae was higher in AgCLP group rats than AgS group rats and AgMET group rats; while metformin could increase the proportion of Firmicutes, Lactobacillus, Ruminococcus_1 and Lactobacillus_johnsonii in aged SALI rats. Moreover, Prevotella_9, Klebsiella and Escherichia_Shigella were correlated positively with the inflammatory factor IL-1 in the lung tissues; Firmicutes was correlated negatively with the inflammatory factor IL-1 and IL-6 in the lung tissues. Conclusions: Our findings suggested that metformin could improve SALI and gut microbiota in aged rats, which could provide a potential therapeutic treatment for SALI in aged sepsis.

Retracted: Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitis.

This publication has been retracted by the Editor due to the identification of non-original figure images that raise concerns regarding the credibility and originality of the study. Reference: You-Dong Wan, Rui-Xue Zhu, Zhong-Zheng Bian, Xin-Ting Pan. Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitisy. Med Sci Monit, 2019; 25: 4609-4616. DOI: 10.12659/MSM.914538.

A Single-Center, Randomized, Double-Blind Study of 94 Patients Undergoing Surgery for Cerebral Glioma to Compare Postoperative Thromboprophylaxis with and without Rivaroxaban.

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Safety of mechanical and manual chest compressions in cardiac arrest patients: A systematic review and meta-analysis.

AIM: Summarise the evidence regarding the safety of mechanical and manual chest compressions for cardiac arrest patients. METHODS: Two investigators separately screened the articles of EMBASE, PubMed, and Cochrane Central databases. Cohort studies and randomized clinical trials (RCTs) that evaluated the safety of mechanical (LUCAS or AutoPulse) and manual chest compressions in cardiac arrest patients were included. A meta-analysis was performed using a random effects model to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The primary outcome was the rate of overall compression-induced injuries. The secondary outcomes included the incidence of life-threatening injuries, skeletal fractures, visceral injuries, and other soft tissue injuries. RESULTS: The meta-analysis included 11 trials involving 2,818 patients. A significantly higher rate of overall compression-induced injuries was found for mechanical compressions than manual compressions (OR, 1.29; 95% CI, 1.19-1.41), while there was no significant difference between the two groups in respect of the rate of life-threatening injuries. Furthermore, both modalities shared similar incidences of sternal fractures, vertebral fractures, lung, spleen, and kidney injuries. However, compared to mechanical compressions, manual compressions were shown to present a reduced risk of posterior rib fractures, and heart and liver lesions. CONCLUSIONS: The findings suggested that manual compressions could decrease the risk of compression-induced injuries compared to mechanical compressions in cardiac arrest patients. Interestingly, mechanical compressions have not increased the risk of life-threatening injuries, whereas additional high-quality RCTs are needed to further verify the safety of mechanical chest devices. TRIAL REGISTRY: INPLASY; Registration number: INPLASY2020110111; URL: https://inplasy.com/.

[Mechanism of gasdermin D on intestinal injury in severe acute pancreatitis by mediating pyroptosis].

OBJECTIVE: To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP). METHODS: The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 µg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1ß, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue. RESULTS: The serum levels of IL-1ß and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1ß (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P < 0.05]; and the levels of IL-1ß and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1ß (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P < 0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2-ΔΔCt: 0.26±0.12 vs. 1.01±0.37, 0.67±0.32, both P < 0.05), while the expression of lnc uc.173 in the siRNA-SAP group was significantly higher than that in the SAP model group (2-ΔΔCt: 0.60±0.39 vs. 0.26±0.12, P < 0.05). Immunohistochemistry showed that ZO-1 and Occludin proteins in the NS group were distributed along the epithelial cells of the intestinal mucosa, showing a strong expression; ZO-1 and Occludin expressions were significantly reduced in the SAP model group and siRNA-SAP group, but the expressions in the siRNA-SAP group was higher than that in the SAP model group. Western blotting showed that the expression level of GSDMD protein in the intestinal tissues of the SAP model group was significantly higher than that of the NS group and the siRNA-NS group [GSDMD protein (GSDMD-N/ß-actin): 1.99±0.46 vs. 1, 1.00±0.78, both P < 0.05]. Compared with the SAP model group, the expression of GSDMD protein in the siRNA-SAP group was significantly decreased [GSDMD protein (GSDMD-N/ß-actin): 1.42±0.42 vs. 1.99±0.46, P < 0.05]. CONCLUSIONS: The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.

Downregulating Gasdermin D Reduces Severe Acute Pancreatitis Associated with Pyroptosis.

BACKGROUND Intestinal injury plays a key role in the pathogenesis of severe acute pancreatitis (SAP). In this study, we investigated the protective function of downregulated Gasdermin D (GSDMD) in intestinal damage in a mouse model of severe acute pancreatitis (SAP). MATERIAL AND METHODS Twenty-four healthy male C57BL/6 mice were randomly divided into 4 groups - the NS group, the siRNA-NS group, the SAP group, and the siRNA-SAP group - with 6 mice in each group. SAP was induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes of pancreatic and the intestinal mucosa and the relative gene and protein expressions in each group were compared, and the levels of GSDMD and serum IL-1ß and IL-18 were evaluated after induction of the SAP model. RESULTS The mice in the SAP group were in more serious condition than those in the siRNA-SAP group, with various degrees of edema and hemorrhage in the intestinal tract. Under an optical microscope, the pathological changes of pancreatic tissue such as edema, inflammatory cell infiltration, and the damage of lobular structural were gradually increased in the SAP group and the siRNA-NS group. In addition, intestinal mucosal damage and intestinal villus breakage were found in the SAP group and the siRNA-NS group, and the latter was lighter than the former. Compared with the SAP group, the level of GSDMD protein expression in the siRNA-SAP group was lower, and the serum levels of IL-1ß and IL-18 were higher in the SAP group and siRNA-SAP group (P<0.05). Immunohistochemical analysis showed the occludin and ZO-1 proteins in the NS group had a strong brown linear signal, while the brown-positive signals were weaker in the siRNA-SAP group and the SAP group. CONCLUSIONS Downregulating GSDMD protein can reduce pancreatitis associated with pyroptosis.

Effect of probiotics on length of hospitalization in mild acute pancreatitis: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Acute pancreatitis is the leading cause of hospitalization for acute gastrointestinal disease worldwide. The effects of probiotics in mild acute pancreatitis have not been studied. We hypothesized that the administration of probiotics may accelerate the recovery of intestinal function and shorten the length of hospital stay (LOS) in patients with mild pancreatitis. AIM: To investigate the value of probiotics in reducing the LOS in patients with mild acute pancreatitis. METHODS: We conducted a double-blind randomized clinical trial to evaluate the effects of probiotics administered to patients with mild acute pancreatitis at a tertiary medical center. The patients were given probiotics capsules (a mixed preparation of Bacillus subtilis and Enterococcus faecium) or placebo. The primary study endpoint was the LOS. The secondary endpoints included time to abdominal pain relief, recurrent abdominal pain, and time to successful oral feeding. RESULTS: A total of 128 patients were included, with 64 patients in each arm. The severity of illness and the etiological distribution of disease were similar in the two groups. There was a significant reduction in the LOS in the probiotics treatment group vs the placebo group (5.36 ± 0.15 vs 6.02 ± 0.17 d, P < 0.05). The probiotics group was associated with a shorter time to abdominal pain relief and time to successful oral feeding (P < 0.01 for both) than the placebo group. No statistical difference was found in recurrent abdominal pain between the two groups. CONCLUSION: The study results showed that the administration of probiotics capsules is associated with a shorter duration of hospitalization in patients with mild acute pancreatitis.

Bile Acid Supplementation Improves Murine Pancreatitis in Association With the Gut Microbiota.

Disorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted the stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. The gut microbiota is known to regulate bile acid production and signaling, and our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors of TUDCA. Taken together, our study shows that supplementation with BAs could reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.

Immunosuppressive drugs to reduce the mortality rate in patients with moderate to severe paraquat poisoning: A Meta-analysis.

The benefits and adverse effects of immunosuppressive drugs (ISDs) in patients with paraquat (PQ) poisoning have not been thoroughly assessed. This meta-analysis study aims to evaluate the effect of ISDs in patients with moderate to severe PQ poisoning. We searched PubMed, Embase, Cochrane Library, Ovid Medline, CNKI and Wanfang Data from inception to January 2019. The Mantel-Haenszel method with a random-effects model was used to calculate the pooled relative risks (RRs) and 95% Confidence Intervals (CIs) as described by DerSimonian and Laird. An L'Abbé plot was drawn to explore the relationship between the degree of poisoning and mortality. Four randomized controlled trials, two prospective and seven retrospective studies were identified. ISDs were significantly associated with reduced mortality (RR 0.76; 95% CI, 0.58-0.99) and the incidence rate of multiple-organ dysfunction syndrome (MODS) (RR 0.63; 95% CI, 0.48-0.83) in patients with moderate to severe PQ poisoning. They were not associated with an increased incidence rate of hepatitis and reduced incidence rate of acute renal failure and hypoxia. The L'Abbé plot results showed a slight increase in mortality rate in the ISD group with increased mortality in the placebo group. This indicates a possible advantage of ISDs in most of the patients with severe PQ poisoning. These findings suggest that ISDs may reduce the mortality and incidence rate of MODS in moderate to severe PQ poisoning patients, and severe PQ poisoning patients might benefit more from ISDs.

Association Between Gut Bacterial Diversity and Mortality in Septic Shock Patients: A Cohort Study.

BACKGROUND Gut bacterial diversity is decreased in a proportion of patients with septic shock. We attempted to validate the hypothesis that low bacterial diversity increases the risk of mortality. MATERIAL AND METHODS All patients with septic shock seen at 2 medical center from 2016 through 2019 were included in this cohort study. Total DNA was isolated from stool, and high-throughput sequencing was performed. Clinical data were extracted from patient medical records and hospital databases. Patients were grouped by gut microbiota bacterial diversity (measured by Shannon diversity index) on presentation. We used logistic regression analysis to evaluate the risk of 28-day mortality in septic patients with low Shannon diversity index. RESULTS Of the 150 patients enrolled in this study, low bacterial diversity (Shannon index <3.0) was found in 80 patients and normal diversity (Shannon index ≥3.0) was found in 70 patients. Low diversity was associated with a higher unadjusted mortality risk, compared to those with normal diversity (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.35-2.83). However, this result became non-significant after adjusting the confounding factors such as age, sex, severity of disease, comorbid status, usage of probiotics, enteral nutrition, and antimicrobial drugs (OR 1.93, 95% CI 0.55-2.69). CONCLUSIONS Our study does not support that low gut bacterial diversity is an independent risk factor for mortality in intensive care unit patients with septic shock.

Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitis.

BACKGROUND Gut microbiota dysbiosis plays a key role in pathogenesis of severe acute pancreatitis (SAP). In this study, we explored the protective effects of the p38 MAPK inhibitor, SB203580, against gut inflammation and microbiota dysbiosis induced by pancreatic duct injection with 3.5% sodium taurocholate in an SAP rat model. MATERIAL AND METHODS Ninety male Sprague-Dawley rats were randomly assigned to sham-operated, SAP model, and SAP plus SB203580 groups (n=30/group). Histological examination was conducted to assess gut and pancreatitis injury. The levels of amylase, D-lactate, diamine oxidase, tumor necrosis factor alpha, IL-6, IL-1ß, and phospho-p38MAPK in the plasma and intestine were evaluated at 3, 6, or 12 h after SAP induction. The gut microbiome was investigated based on16S rDNA gene sequencing at 12 h after SAP induction. RESULTS Histological examination revealed edema and inflammatory infiltrations in the pancreas and distal ileum. The expression of tumor necrosis factor alpha, IL-1ß, and IL-6 in plasma and distal ileum was increased in the SAP group, which were restored after treatment with SB203580. Significantly lower bacterial diversity and richness was found in the SAP group. In the SAP group, the abundance of Bacteroidetes and Firmicutes was decreased, and there was a higher proportion of Proteobacteria at the phylum level. The SAP plus SB203580 group exhibited significantly less damage to the gut microbiota, with higher bacterial diversity and a more normal proportion of intestinal microbiota. CONCLUSIONS SB203580 mediated suppression of the p38 MAPK signaling pathway via reduced gut inflammatory response and microbiota dysbiosis.

Gut Microbiota Disruption in Septic Shock Patients: A Pilot Study.

BACKGROUND The composition of the intestinal microbiota and its effect on septic shock patients in the intensive care unit (ICU) is unknown. In the present study we explored the hypothesis that bacterial diversity is decreased in septic shock patients and that this diversity may be improved by use of probiotics or enteral nutrition. MATERIAL AND METHODS A total of 15 stool samples were collected prospectively from septic shock patients in the ICU, while 15 samples from healthy subjects served as controls. Bacterial DNA was submitted for 16S rDNA gene sequencing. The relationship between intestinal microbiota and prognosis was evaluated. RESULTS Significantly lower bacterial diversity was found in septic shock patients compared with healthy subjects (p<0.05). However, there was no difference in bacterial diversity in the presence or absence of probiotics (p=0.59), enteral nutrition (p=0.59), or in-hospital death (p=0.93) in septic shock patients. A high abundance of Proteobacteria and Fusobacteria was observed in most septic shock patients, whereas low abundance was observed in healthy subjects (mean relative proportion: 23.71% vs. 3.53%, p<0.05; 1.27% vs. 0.12%, p=0.59). CONCLUSIONS Bacterial diversity was decreased, and 1 or 2 rare bacterial species were overgrown in septic shock patients. Bacterial diversity was not improved by use of probiotics or enteral nutrition. The small sample size of our study limits the interpretation of results.

[Efficacy and safety of nalbuphine on analgesia of patients in intensive care unit].

OBJECTIVE: To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). METHODS: A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. RESULTS: A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation II (APACHE II) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg×kg-1×h-1 in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) µg×kg-1×h-1 in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. CONCLUSIONS: Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

Role of silodosin as medical expulsive therapy in ureteral calculi: a meta-analysis of randomized controlled trials.

The objective of this study is to investigate the efficacy of silodosin in medical expulsive therapy (MET) for ureteral stones. We conducted a systematic review and meta-analysis to determine the efficacy and safety of silodosin in MET for ureteral calculi. We searched PubMed, Embase, Medline, Central (the Cochrane Library, Issue 1,2013), Google Scholar from the inception to March 2015 for randomized controlled trials (RCTs), comparing silodosin with tamsulosin or control on ureteral stone passage. Eight RCTs with a total of 1145 ureteral stone patients (300 patients in the control group, 287 patients in the tamsulosin group, 558 patients in the silodosin group) were included in this meta-analysis. When compared with control, silodosin significantly improved expulsion rate of distal ureteral stones (RR: 1.42; 95% CI, 1.21-1.67; P < 0.0001), while there was no significant difference between silodosin and the control in expulsion rate of proximal (RR: 0.99; 95% CI, 0.69-1.43; P < 0.97) or mid (RR: 1.13; 95% CI, 0.60-2.16; P < 0.0001) ureteral stones. There was no significant difference between silodosin and tamsulosin in terms of expulsion time (WMD: -2.47; 95% CI, -5.32 to 0.39; P = 0.09), analgesic use (WMD: -0.39; 95% CI, -0.91 to 0.13; P = 0.14) and retrograde ejaculation rate (RR: 1.85; 95% CI, 0.95-3.59; P = 0.07) in MET for distal ureteral stones. However, silodosin provided a significantly higher expulsion rate (RR: 1.25; 95% CI, 1.13-1.37; P < 0.0001) than tamsulosin for distal ureteral stones. Silodosin significantly improved expulsion rate of distal ureteral stones and was clinically superior to tamsulosin. Silodosin was ineffective in MET for proximal and mid ureteral stones. More RCT studies are needed to compare the efficacy of silodosin versus tamsulosin in MET for distal ureteral stones.

Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

BACKGROUND: Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. METHODS: Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. RESULTS: Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. CONCLUSIONS: Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation.

The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era.

BACKGROUND: Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era. METHODS: Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted. RESULTS: A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42-1.01), or long-term mortality (RR 0.79; 95% CI, 0.47-1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25-0.67). CONCLUSION: In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.

Efficacy and Safety of Corticosteroids for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis.

BACKGROUND: Corticosteroids are an option in the treatment of community-acquired pneumonia (CAP). However, the benefits and adverse effects of corticosteroids, especially in severe CAP, have not been well assessed. METHODS: PubMed, Embase, and Cochrane library databases from inception to May 2015 were searched. Randomized controlled trials (RCTs) and cohort studies that evaluated use of corticosteroids in adult patients with CAP were included. The quality of outcomes was evaluated using Grading of Recommendations Assessment, Development and Evaluation methodology. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% CIs. RESULTS: Nine eligible RCTs (1,667 patients) and six cohort studies (4,095 patients) were identified. The mean corticosteroid dose and treatment duration were 30 mg/day methylprednisolone for 7 days. Corticosteroids did not have a statistically significant effect on mortality (RR, 0.72; 95% CI, 0.43-1.21; evidence rank, low) in patients with CAP and patients with severe CAP (RCTs: RR, 0.72; 95% CI, 0.43-1.21; evidence rank, low; cohort studies: RR, 1.00; 95% CI, 0.86-1.17 ). Corticosteroids treatment was associated with a decreased risk of ARDS (RR, 0.21; 95% CI, 0.08-0.59) and may reduce lengths of hospital and ICU stay, duration of IV antibiotic treatment, and time to clinical stability. Corticosteroids were not associated with increased rates of adverse events. CONCLUSIONS: Short-term treatment with corticosteroids is safe and may reduce the risk of ARDS, shortening the length of the disease in patients with CAP.

Aspirin might reduce the incidence of pancreatic cancer: A meta-analysis of observational studies.

Although there is evidence that non-steroidal anti-inflammatory drugs (NSAIDs) might be able to prevent pancreatic cancer, the findings from epidemiological studies have been inconsistent. In this paper, we conducted a meta-analysis of observational studies to examine this possibility. We searched PubMed and Embase for observational (cohort or case-control) studies examining the consumption of aspirin and other NSAIDs and the incidence of or mortality rates associated with pancreatic cancer. Twelve studies including approximately 258,000 participants in total were analysed. The administration of aspirin significantly reduced the incidence of pancreatic cancer (8 studies; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.62 to 0.96; I(2) = 74.2%) but not the mortality associated with it (2 studies; OR = 0.94; 95% CI = 0.73 to 1.22). Specifically, frequent aspirin use was associated with reduced pancreatic cancer incidence (OR = 0.57; 95% CI = 0.39 to 0.83 for high frequency; OR = 0.57; 95% CI = 0.38 to 0.84 for medium frequency). The summary ORs regarding the incidence of pancreatic cancer and either non-aspirin NSAIDs use (OR = 1.08; 95% CI = 0.90 to 1.31) or overall NSAIDs use (OR = 0.97; 95% CI = 0.86 to 1.10) were not significant. In conclusion, aspirin use might reduce the incidence of pancreatic cancer; however, this finding should be interpreted with caution because of study heterogeneity.