Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hospital Mortality ; Cohort Studies ; Prospective Studies ; Water-Electrolyte Imbalance ; Sepsis ; Intensive Care Units ; Retrospective Studies

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; prevention & control ; Disease Outbreaks ; Emergencies ; Hospitals, General ; Humans ; Internet ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Objective:To investigate the expression of IKBKE and NF-κB in pancreatic cancer, and to explore the effect of IKBKE on pancreatic cancer proliferation and migration.Methods:Immunohistochemistry staining was used to study the expression of IKBKE and NF-κB in tissues of 61 pancreatic cancer patients admitted to the Second Hospital of Tianjin Medical University from January 2012 to January 2017 and 13 normal pancreatic tissues. The correlations between those expression to clinicopathological features were analyzed. Lentivirus mediated RNAi was transfected into pancreatic cancer cells to block IKBKE. Western blot was performed to test the silencing effeciency; CCK-8 and plate clone and scratch assays were used to investigate the proliferation and migration of pancreatic cancer.Results:Immunohistochemical staining showed that 60 (98.4%) of IKBKE staining were weakly positive, positive, and strongly positive in pancreatic cancer tissues, which were significantly higher than normal pancreatic tissues(76.9% cases were weakly positive and the rest were negative), and the differences were statistically significant ( P<0.05). All cases of NF-κB exhibited weakly positive expression and above in pancreatic cancer tissues, which was markedly higher than normal tissues (30.8% cases were weak positive and the rest were negative staining), statistically significant ( P<0.05). Survival analysis showed that patients with high level of IKBKE showed a shorter overall survival ( P<0.05). CCK-8, plate cloning and scratch assays showed that the proliferation and migration of were significantly decreased in IKBKE knocking down group ( P<0.05). Conclusions:IKBKE and NF-κB are highly expressed in pancreatic cancer, and IKBKE is correlated with NF-κB in pancreatic cancer. Blocking of IKBKE could distinctly inhibit the proliferation and migration of pancreatic cancer.

AIM:To investigate the protective effect of mucin 2(MUC2)on intestinal mucosa of colitis model mice,and to explore the correlation between the expression of anti-CBir1 flagellin antibody and MUC2.METHODS:The mice were randomly divided into normal control group,2,4,6-trinitrobenzenesulfonic acid(TNBS)group,lipopolysaccha-ride(LPS)+ovalalbumin(OVA)+TNBS group and ketotifen+TNBS group.The expression of MUC2 in colon tissue was determined by PAS staining and immunohistochemistry, and the anti-CBir1 antibody level in the serum of mice in each group was measured by ELISA.RESULTS:The scores of disease activity index and histological index in TNBS group were higher than those in normal control group(P<0.05).The scores in LPS +OVA+TNBS group were much higher than those in TNBS group(P<0.05).However, the values in ketotifen +TNBS group were lower than those in TNBS group (P<0.05).PAS staining showed a decrease in goblet cells in TNBS group.Compared with TNBS group,the colonic mu-cosa integrity in LPS+OVA+TNBS group was destroyed, and the number of goblet cells in ketotifen +TNBS group in-creased significantly.Immunohistochemical staining showed that the expression of MUC 2 in the intestinal tract of each mo-del group was basically consistent with the results of PAS staining.The serum anti-CBir1 antibody level in TNBS group was higher than that in normal control group(P<0.05), and that in LPS+OVA+TNBS group was significantly higher than that in TNBS group(P<0.05),whereas that in ketotifen +TNBS group was decreased slightly(P<0.05).CONCLU-SION:MUC2 plays a protective role in the pathogenesis of colitis in mice,and there is a negative correlation between the expression of MUC2 and the bacterial flagellin in the intestinal mucosa of mice with colitis.

Objective To investigate the clinical effect of transurethral resection of prostate (BPH) with plasmakinetic resection of prostate (PKURP) combined with laparoscopic total extraperitoneal inguinal hernia repair (TEP) in the treatment of benign prostatic hyperplasia (BPH) with inguinal hernia. Methods Retrospective analysis of surgery in our hospital in 59 cases of BPH with clinical data of patients with inguinal hernia, which received a first PKURP again for TEP staging surgery patients (control group) 28 cases; accept patients underwent PKURP surgery combined with TEP (observation group) 31 cases, compared two groups of operation time, bleeding volume, operation success rate, rate of postoperative complications and recurrence. Results The operation time and the operation of two groups of TEP and PKURP success rate comparison, the difference was not statistically significant (P > 0.05); the amount of bleeding in the observation group was significantly lower than that in the control group, and the total hospitalization time and total cost were significantly shorter than those in the control group, the difference was statistically significant (P < 0.05); no statistical significance two the postoperative complications of group differences (P > 0.05). Conclusion PKURP combined with TEP is safe and effective in the treatment of BPH with the same period of inguinal hernia, and can reduce the bleeding, reduce medical costs, and avoid the trauma and pain two surgery and anesthesia, especially has positive significance for the elderly and patients with poor surgical tolerance.

Objective: To evaluate the effectiveness of enteral nutrition in children with accidental upper gastrointestinal injury. Methods: The medical records of 128 patients with mechanical or chemical gastrointestinal mucosal injury, who were hospitalized in Department of Gastroenterology, Children's Hospital of Zhejiang University School of Medicine from January 1, 2011 to December 30, 2017, were collected. All cases were treated with enteral nutrition. The clinical features and etiologies were retrospectively analyzed. Weight-for-age Z score and lab findings including white blood cells, C-reactive protein, neutrophils, albumin, prealbumin, urea nitrogen and hemoglobin before and after treatment were extracted. The clinical characteristics, the duration of enteral nutrition and gastrointestinal mucosal healing between different etiologies were further analyzed. Normal distribution variables and categorized variables were compared with t test and χ² test respectively, and abnormal distribution data was compared with Wilcoxon test. Results: Among all the cases, 77 were males and 51 were females. The average age was (29±22) months. The mean duration of hospitalization and enteral nutrition were (11±7)d and (27±20)d respectively. Vomiting was the most common clinical presentation (72 cases, 56.3%). In 79 cases the problems were caused by mechanical injury, among which coins were most commonly seen. The rest 49 cases were caused by chemical injury. However, the duration of hospitalization ((13±8) d vs. (10±6)d, t=-3.089, P=0.002) and enteral nutrition ((39±22) vs. (19±14) d, t=-5.365, P=0.000) were longer in children with chemical injury than those with mechanical injury. A total of 112 cases got complete blood count and C-reactive protein both before and after enteral nutrition. Inflammatory markers, including leukocytes ((7.7±2.7) ×10⁹/L vs. (13.7±5.0) ×10⁹/L, t=12.244, P <0.05), neutrophils ((3.4±1.9)×10⁹/L vs. (9.4±4.6) ×10⁹/L, t=13.655, P<0.05), and C-reactive proteins (5.0(3.0,7.8) vs. 13.5(6.0,40.5) mg/L, Z=7.776, P <0.05) were significantly decreased. The nutritional markers, including the weight-for-age z score (-0.1 ± 1.0 vs. 0.0 ± 1.0, t=-2.622, P=0.010) and the prealbumin (0.1 ± 0.1 vs. 0.2 ± 0.0 g/L, t=-3.671, P=0.001) were significantly increased. Fifty-five (82.1%) children in mechanical injury group recovered in 4 weeks, while 27 (79.4%) children in chemical injury group recovered in 7 weeks. Conclusion Enteral nutrition can provide adequate nutritional requirements for children with upper gastrointestinal injury, and may help to decrease imflammation and improve mucosal healing.

OBJECTIVE: To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms. METHODS: Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed. RESULTS: Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01). CONCLUSIONS Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Dipeptides ; Humans ; Indoles ; Liver Neoplasms ; Male ; Mice ; Mice, Inbred BALB C ; Mitochondrial Proteins

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.
Adult ; Aged ; Asian People ; Double-Blind Method ; Erectile Dysfunction/drug therapy* ; Female ; Humans ; Male ; Middle Aged ; Patient Safety ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Product Surveillance, Postmarketing ; Prospective Studies ; Tadalafil/therapeutic use* ; Treatment Outcome ; Young Adult

Objective To analyze the risk factors of microvascular complications in patients with type 2 diabetes mellitus (T2DM).Methods The demographic and clinical data of 5078 T2DM patients in six communities of Shanghai were collected during September 2014 to April 2015. The risk factors of microvascular complications in T 2DM were analyzed by classification tree model .Results Among 5078 T2DM patients there were 1007 cases of diabetic retinopathy (DR) (21.1%) and 1937 cases of diabetic nephropathy (DN) (38.4%).The classification tree models showed that the risk factors of DR were higher hemoglobin A1C ( HbA1c), fasting blood glucose ( FBG), postprandial blood glucose ( PBG) and triacylglycerol ( TG) levels;longer course of disease and younger age of onset .The model showed that the risk factors of DN were higher HbA1c, FBG, hypertension, PBG, body mass index ( BMI ) and triacylglycerol (TG) levels;and lower high-density lipoprotein (HDL) level.The HbA1c, course of disease and PBG were more closely related to DR and HbA 1c, hypertension and FBG were more closely related to DN.Conclusion HbA1c is the most important risk factor to microvascular complications; FBG and PBG are independent risk factors of microvascular complications;the course of disease and hypertension are risk factors of DR and DN , respectively .