Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

NLRP3 inflammasome-mediated Pyroptosis induce Notch signal activation in endometriosis angiogenesis.

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that not only causes severe pelvic pain and infertility but also increased risk for ovarian carcinogenesis in women of reproductive age. Here, we found that angiogenesis was increased and accompanied with up-regulation of Notch1 in human endometriotic tissue sample, which is associated with pyroptosis induced by activation of endothelial NLRP3 inflammasome. Further, in endometriosis model induced in wild type and NLRP3-deficient (NLRP3-KO) mice, we found that deficiency of NLRP3 suppressing the development of endometriosis. In vitro, inhibiting the activation of NLRP3 inflammasome prevents LPS/ATP-induced tube formation in endothelial cells. Meanwhile, knockdown NLRP3 expression by gRNA disrupt the interaction between Notch1 and HIF-1α under the inflammatory microenvironment. This study demonstrates that activation of NLRP3 inflammasome-mediated pyroptosis affects angiogenesis in endometriosis via Notch1-dependent manner.

Berberine alleviates NLRP3 inflammasome induced endothelial junction dysfunction through Ca2+ signalling in inflammatory vascular injury.

BACKGROUND: Berberine has received rising attention for its application in cardiovascular disease because of its relationship with inflammation. The endothelial NLRP3 inflammasome triggers inflammatory vascular injury which would lead to cardiovascular disease. Endothelial calcium signalling plays a crucial role in both the activation of NLRP3 inflammasome and endothelial cells dysfunction. However, the efficacy of BBR on the endothelial NLRP3 inflammasome in inflammatory vascular injury remains unknown. PURPOSE: In this study, we focused on the NLRP3 pathway to determine whether BBR regulates endothelial junction function in inflammatory vascular injury. METHODS: The integrity of the junction proteins VE-cadherin (VEC) and zonula occludens-1 (ZO-1) detected by immunofluorescence and immunoblotting was used to determine the therapeutic effect of BBR (50, 100, or 200 mg/kg/day) in LPS (100 µg/kg/day)-induced inflammatory vascular injury in mice and mouse microvascular endothelial cells (MECs) treated with LPS (1 µLPS ) and ATP (5 mM). Endothelial permeability was assessed by FITC-labelled dextran and trans-endothelial electrical resistance (TEER) in vitro. The assembly and activation of NLRP3 inflammasomes were detected by western blotting and immunofluorescence. Pharmacophore-based virtual molecular docking studies and calcium imaging analyses were used to determine the interaction of BBR with the ATP-gated Ca2+ channel P2X7R (purinergic P2X receptor 7) in the context of inflammatory vascular injury. RESULTS: BBR recovered the expression of ZO-1 and VEC and inhibited endothelial NLRP3 inflammasome activation in coronary microvascular endothelium and in MECs. These results suggested a crucial role of the NLRP3 inflammasome in BBR-regulated endothelial integrity. Further analysis demonstrated that BBR treatment suppressed the binding of TXNIP (thioredoxin interacting protein) with NLRP3. Intriguingly, eliminating extracellular Ca2+ showed a similar effect as BBR. Virtual docking analysis indicated that R574 of P2X7R is a potential target for BBR binding. Ca2+ imaging showed that BBR inhibited the Ca2+ influx in response to ATP, supporting the potential interaction of BBR with P2X7R. CONCLUSIONS: These findings suggest that BBR exhibits potential and specific therapeutic value by targeting calcium signals and the endothelial NLRP3 inflammasome in inflammatory vascular injury.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism: a meta-analysis.

OBJECTIVE: Several trials had compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin for acute venous thromboembolism, but the results were incomplete. This updated review comprehensively assessed the efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism. DESIGN: Meta-analysis of randomised control trials. Six databases were searched from January 2000 to December 2018. SETTING: Adult patients had got non-vitamin K antagonist oral anticoagulants or warfarin for venous thromboembolism. PARTICIPANTS: Randomised control trials that compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin. MAIN OUTCOME MEASURES: The efficacy and safety of non-vitamin K antagonist oral anticoagulants . RESULTS: Seven studies involving 29,879 cases were included, among which 14,943 cases were assigned to non-vitamin K antagonist oral anticoagulants group and 14,936 cases to warfarin group. Meta-analysis showed that compared with warfarin, recurrent venous thromboembolism (odds ratio 0.94 [95% confidence interval 0.81 to 1.11]), death related to venous thromboembolism or fatal pulmonary embolism (odds ratio 1.00 [95% confidence interval 0.63 to 1.60]), symptomatic deep-vein thrombosis (odds ratio 0.88 [95% confidence interval 0.72 to 1.09]), symptomatic nonfatal pulmonary embolism (odds ratio 1.03 [(95% confidence interval 0.82 to 1.30]) and all deaths (odds ratio 0.92 [95% confidence interval 0.76 to 1.12]) are similar in non-vitamin K antagonist oral anticoagulants group, but major bleeding event (odds ratio 0.61 [95% confidence interval 0.50 to 0.75]) and clinically relevant non-major bleeding event (odds ratio [95% confidence interval 0.53 to 0.85]) are less in non-vitamin K antagonist oral anticoagulants group. . CONCLUSIONS: For the treatment of venous thromboembolism, non-vitamin K antagonist oral anticoagulants is as effective as warfarin, and has a better safety profile than warfarin.

Efficacy and safety of methylprednisolone against acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS. MATERIAL AND METHODS: The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43-0.95, I2 = 42%); the time of mechanical ventilation (MD) = -2.70, 95% CI: -3.31 to -2.10; I2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34-1.86; I2 = 58%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.

Contribution of TFEB-mediated autophagy to tubulointerstitial fibrosis in mice with adenine-induced chronic kidney disease.

Autophagy has been implicated in the pathogenesis of chronic kidney disease (CKD). Transcription factor EB (TFEB) is a master controller of autophagy. However, the pathophysiological roles of TFEB in modulating autophagy and tubulointerstitial injury in CKD are unknown. This study aimed to determine whether TFEB-mediated autophagy contributed to the tubulointerstitial injury in mice with CKD. After the mice were treated with an adenine diet (0.2 % adenine) for 8 weeks, the development of CKD was observed to be characterised by increased levels of plasma blood urea nitrogen (BUN), creatinine (Cre), tubulointerstitial inflammation and fibrosis. Immunohistochemical and Western blot analysis further revealed that TFEB and autophagy genes were significantly up-regulated in the kidney of the mice with adenine-induced CKD, and this increase was mostly found in the tubular epithelial cells. Interestingly, a similar expression pattern of TFEB-autophagy genes was observed in tubular epithelial cells in the kidney tissue of patients with immunoglobulin A (IgA) nephropathy. Moreover, a pathogenic role of TFEB in adenine-induced CKD was speculated because the pharmacological activation of TFEB by trehalose failed to protect mice from tubulointerstitial injuries. In the epithelioid clone of normal rat kidney cells (NRK-52E), the activation of TFEB by trehalose increased autophagy induction, cell death and inflammatory cytokine (Interleukin-6, IL-6) release. Collectively, these results suggested that the activation of TFEB-mediated autophagy might cause autophagic cell death and inflammation in tubular epithelial cells, contributing to renal fibrosis in adenine-induced CKD. This study provided novel insights into the pathogenic role of TFEB in CKD associated with a high purine diet.

[Inferior vena cava diameter combined with lung ultrasound B-line score to guide fluid resuscitation in patients with septic shock].

OBJECTIVE: To compare the effect of goal-directed fluid resuscitation and bedside ultrasound-guided fluid resuscitation in patients with septic shock, and to evaluate the application value of bedside ultrasound in fluid resuscitation of patients with septic shock. METHODS: Forty patients with septic shock admitted to department of critical care medicine of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2018 to October 2019 were enrolled, and they were divided into early goal-directed therapy (EGDT) group and ultrasound group according to random number table, with 20 patients in each group. Bacterial cultures were routinely performed, and all patients received conventional treatments, such as anti-infection, nutritional support and organ support. All patients were given initial fluid resuscitation (30 mL/kg). The patients in the EGDT group continued to be given fluid resuscitation according to the guidelines (EGDT 6-hour target) after the initial fluid resuscitation. The patients in the ultrasound group were given follow-up fluid resuscitation based on bedside ultrasound inferior vena cava diameter and lung ultrasound B-line score after initial fluid resuscitation. The general data, main laboratory indexes and efficacy indexes of the two groups were compared, including 6-hour blood pressure achieved rate [mean arterial pressure (MAP) ≥ 65 mmHg (1 mmHg = 0.133 kPa) was defined as blood pressure reaching standard], 24-hour resuscitation fluid volume, 24-hour norepinephrine (NE) consumption, 24-hour oxygenation index (PaO2/FiO2) and 24-hour clearance of lactic acid (LCR) were compared between the two groups. The survival curve of intensive care unit (ICU) was drawn by Kaplan-Meier analysis. RESULTS: There was no significant difference in the gender, age, heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), underlying diseases, sequential organ failure assessment (SOFA) score, PaO2/FiO2, blood lactic acid (Lac), D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), total bilirubin (TBil) and serum creatinine (SCr) baselines at admission between the two groups. There was also no significant difference in the 6-hour target blood pressure achieved rate [65.0% (13/20) vs. 70.0% (14/20)], 24-hour total NE dosage [mg: 20.0 (10.0, 66.5) vs. 30.0 (10.5, 85.0)], 24-hour PaO2/FiO2 (mmHg: 274.6±123.8 vs. 243.1±124.0) or 24-hour LCR [9.1% (-34.5%, 58.0%) vs. 44.0% (-24.1%, 81.3%)] between the EGDT group and ultrasound group (all P > 0.05), but the 24-hour total fluid infusion in the ultrasound group was significantly less than that in the EGDT group (mL: 2 783.1±704.2 vs. 3 692.0±1 433.1, P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate of ICU between the two groups was not statistically significant (Log-Rank test: χ2 = 0.088, P = 0.767). CONCLUSIONS: Bedside ultrasound protocol combined inferior vena cava diameter with lung ultrasound B-line score can be used to guide fluid resuscitation in patients with septic shock, the total fluid infusion is decreased and the risk of oxygenation deterioration is reduced.

[Effects of extracorporeal cardiopulmonary resuscitation for adult patients with out-of-hospital cardiac arrest on survival rate and neurological outcome: a Meta-analysis].

OBJECTIVE: To compare the influences of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional or mechanical cardiopulmonary resuscitation (CCPR/MCPR) on survival rate and neurological outcome for adult patients with out-of-hospital cardiac arrest (OHCA), and to assess the effect of ECPR. METHODS: Databases such as Medline, Embase, ScienceDirect, HighWire, Cochrane Library, Wanfang Database and China National Knowledge Infrastructure (CNKI) were searched from January 2000 to October 2018 to retrieve clinical trials on comparison of the effect of ECPR and CCPR/MCPR on survival rate and neurological outcome of adult patients with OHCA. Thereafter, the studies retrieved were based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated by two researchers. A meta-analysis was performed by using RevMan 5.3 software. Sensitivity analysis was used to evaluate the stability of the results, and funnel plot was used to evaluate publication bias. RESULTS: A total of 12 studies and 2 519 patients were enrolled, including 615 patients receiving ECPR and 1 904 patients receiving CCPR/MCPR. Meta-analysis showed that compared with CCPR/MCPR, ECPR could not improve the short-term (at hospital discharge or within 1 month) survival rate in patients with OHCA [odds ratio (OR) = 2.26, 95% confidence interval (95%CI) = 0.95-5.41, P = 0.07], but could increase long-term (at more than 3 months) survival rate (OR = 3.56, 95%CI = 1.65-7.71, P = 0.001), rate of good neurological outcome at hospital discharge [Glasgow-Pittsburgh cerebral performance categories (CPC) 1-2 was defined as good neurological function; OR = 3.39, 95%CI = 1.73-6.62, P = 0.000 4], and rate of good long-term neurological outcome (OR = 3.45, 95%CI = 2.24-5.32, P < 0.000 01). Sensitivity analysis showed that the overall results did not change significantly, whether using fixed-effect model and random-effect model to analyze the differences of each effect index, or excluding one study with fewer than 50 subjects for data analysis, indicating that the results were more stable. The funnel plot suggested that there was no publication bias in the studies. But due to the small number of studies, the publication bias could not be excluded. CONCLUSIONS: ECPR could not improve the short-term survival rate at hospital discharge or within 1 month in patients with OHCA, but could increase long-term survival rate at more than 3 months, good neurological outcome at hospital discharge and long-term neurological outcome.

Upregulation of microRNA-191 can serve as an independent prognostic marker for poor survival in prostate cancer.

MicroRNA-191 (miR-191) has been identified as being upregulated in several types of cancers, and plays the role of oncogene. The expression of miR-191 has been found to be upregulated in prostate cancer tissues as well as cell lines. In this study, we analyzed the correlation of miR-191 expression with clinicopathologic factors and prognosis in prostate cancer.Prostate cancer tissue samples and adjacent normal prostate tissue samples were collected from 146 patients who underwent laparoscopic radical prostatectomy between April 2013 and March 2018. Student two-tailed t-test was used for comparisons of 2 independent groups. The relationships between miR-191 expression and different clinicopathological characteristics were evaluated using the Chi-squared test. Kaplan-Meier survival plots and log-rank tests were used to assess the differences in overall survival of the different subgroups of prostate cancer patients.miR-191 expression was significantly higher in prostate cancer tissues compared with normal adjacent prostate tissues (P < .001). miR-191 expression was observed to be significantly correlated with Gleason score (P < .001), pelvic lymph node metastasis (P = .006), bone metastases (P < .001), and T stage (P = .005). Kaplan-Meier analysis showed that patients with higher levels of miR-191 had significantly poorer survival than those with lower expression of this miRNA in prostate cancer patients (log rank test, P = .011). Multivariate analysis revealed that miR-191 expression (hazard ratio [HR] = 2.311, 95% confidence interval, [CI]: 1.666-9.006; P = .027) was independently associated with the overall survival of prostate cancer patients.Our results demonstrated that miR-191 might serve as an independent prognostic indicator for prostate cancer patients.

Periodontal ligament fibroblasts migration injury via ROS/TXNIP/Nlrp3 inflammasome pathway with Porphyromonas gingivalis lipopolysaccharide.

Inflammasomes serve as an intracellular machinery to initiate inflammatory response to various danger signals. However, the chronic periodontitis pathological relevance of this inflammasome activation, particularly in periodontal ligament fibroblasts, remains largely unknown. The present study demonstrated that Nlrp3 inflammasome components abundantly expressed in cultured mouse periodontal ligament fibroblasts (mPDLFs). In addition, our data demonstrated that P.g-LPS (Porphyromonas gingivalis Lipopolysaccharide), a major injurious factor during chronic periodontitis, could induce the mPDLFs migration dysfunction and the inhibition of Nlrp3 inflammasome by Isoliquiritigenin (ISO) markedly recovered the migration dysfunction in mPDLFs. And Nlrp3 inflammasome components could be aggregated to form an inflammasome complex on stimulation of P.g-LPS, as shown by fluorescence confocal microscopy. Correspondingly, P.g-LPS induced Nlrp3 inflammasome activation, caspase-1 activation, IL-1ß and HMGB1 release, which were blocked by Nlrp3 inflammasome inhibitor (ISO). Interestingly, reactive oxygen species, TXNIP protein and TXNIP binding to Nlrp3 were markedly increased in mPDLFs with P.g-LPS. Furthermore, ROS generation inhibitor (Apocynin; APO) significantly reduced Nlrp3 inflammasome formation and IL-1ß production in mPDLFs with P.g-LPS. And APO attenuated P.g-LPS-induced TXNIP protein expression and mPDLFs injury. In conclusion, our results demonstrate that ROS/TXNIP/Nlrp3 Inflammasome pathway is a key initiating mechanism necessary for P.g-LPS-induced subsequent mPDLFs inflammatory response leading to chronic periodontitis.

[Diagnostic value of lung ultrasound B-line score in acute heart failure].

OBJECTIVE: To investigate the value of bedside lung ultrasound B-line score in the diagnosis of acute heart failure (AHF). METHODS: A retrospectively analysis was conducted. The adult patients presenting with acute dyspnea in intensive care unit (ICU) of Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2016 to June 2017 were enrolled. An 8-zone lung ultrasound was performed and plasma B-type natriuretic peptide (BNP) level was tested in all patients. AHF was determined as the final diagnosis by two experienced ICU doctors according to the diagnostic criteria of AHF. Patients were divided into two groups: AHF group and non-AHF group. The levels of BNP and B-line score were compared between the two groups, and the diagnostic value of BNP and B-line score in AHF was evaluated. RESULTS: Fifty-six patients were included in this study, with 32 of men and 24 of women, and with an average age of 77.3±8.8. Thirty-six patients were diagnosed as AHF. The level of BNP and lung ultrasound B-line score in AHF group were higher than those in non-AHF group [BNP (ng/L): 1 640.4±1 078.4 vs. 236.9±124.9, B line score: 12.8±5.3 vs. 5.4±1.8, both P < 0.01]. There was a strong correlation between elevated BNP levels and an increased B-lines score (R2 = 0.712, P = 0.000). The receiver operating characteristic curve (ROC) showed that when the cut-off of lung ultrasound B-line score was 8.5, AHF could be discriminated from dyspnea caused by other diseases (sensitivity was 77.8%, specificity was 95%, positive likelihood ratio was 15.56, negative likelihood ratio was 0.23). The area under the ROC curve (AUC) of lung ultrasound B-line score was 0.917 [95% confidence interval (95%CI) = 0.847-0.987, P = 0.000], slightly lower than that of plasma BNP [0.979 (95%CI = 0.951-1.008)]. CONCLUSIONS: Lung ultrasound B-line score was highly specific, but moderately sensitive for identifying patients with AHF.

[Pre-hospital therapeutic hypothermia for survival and neuro-protection after out-of-hospital cardiac arrest: a systematic review and Meta-analysis of randomized controlled trials].

OBJECTIVE: To assess the effectiveness of pre-hospital therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) for survival and neuro-protection. METHODS: Databases such as Medline, ScienceDirect, Embase, Highwire, Cochrane Library, CNKI and Wanfang digital database were searched from January 2000 to March 2017 to retrieve randomized controlled trials (RCTs) on pre-hospital therapeutic hypothermia after OHCA. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A Meta-analysis was performed using the Cochrane Collaboration RevMan 4.3 software. Analysis of publication bias was depicted by funnel plot. RESULTS: Eight studies involving 3 555 cases were included, among which 1 804 cases were assigned to the treatment group and 1 751 cases to the control group. Meta-analysis showed that compared with in-hospital therapeutic hypothermia, pre-hospital therapeutic hypothermia did not improve the survival rate of patients with OHCA [odds ratio (OR) = 1.00, 95% confidence interval (95%CI) = 0.85-1.18, P = 0.99], and neurological outcome at hospital discharge (OR = 0.97, 95%CI = 0.80-1.16, P = 0.71), but the body temperature was significantly lowered at admission [weighted mean difference (SMD) = -0.88, 95%CI = -1.03 to -0.73, P < 0.000 01]. The funnel plot suggested that there was no publication bias in the 8 studies. But due to the low number of studies, the publication bias could not be completely excluded. CONCLUSIONS: Pre-hospital therapeutic hypothermia after OHCA can decrease temperature at hospital admission, but cannot increase the survival rate and neurological outcome at hospital discharge.

Multiple organ dysfunction due to heatstroke after sauna: case report and review of the literature.

Heatstroke usually occurs in summer during heat waves, and few cases occur in winter. We report the case of a 26-year-old man who went through multiple organ dysfunction after sauna in January, and finally was diagnosed as heatstroke.

Laparoscopic Extravesical Submucosal Tunneling Ureteroneocystostomy Combined with Psoas Hitch for Medium-Length Distal Ureteral Defects in Adults.

OBJECTIVE: This study aims to describe the technique and feasibility of laparoscopic submucosal tunneling ureteroneocystostomy in combination with psoas hitch to restore urinary tract continuity in patients showing medium-length distal ureteral defects. MATERIALS AND METHODS: From January 2012 to April 2016, a total of 13 patients (4 males and 9 females) with a mean age of 37 years were performed with the laparoscopic operation of ureteral submucosal tunneling reimplantation combined with psoas hitch. The mean defective length was 5.5 cm (range 4-8 cm). The etiologies included ureteral strictures secondary to endoscopic laser lithotripsy in 2 patients, previous gynecological surgeries in 4, infiltrative ureteral endometriosis in 3, as well as ureteral strictures without obvious causes in the remaining 4. RESULTS: The operations were successfully performed in all patients. The mean operating time was 179 min (range 150-230 min). The mean estimated blood loss was 32 mL (range 15-80 mL). The mean drainage time was 5.8 days (range 4-8 days). No major complications occurred during the perioperative period. The mean follow-up time was 25 months. All patients experienced symptomatic relief and showed good urine drainage. CONCLUSION: Extravesical submucosal tunneling ureteroneocystostomy combined with psoas hitch under laparoscopy is a feasible and effective option for medium-length distal ureteral defects in selected patients.

A new ent-kaurane diterpene from Euphorbia stracheyi Boiss.

The chemical investigation of whole plants Euphorbia stracheyi Boiss from China led to the isolation of one new ent-kaurane diterpene, ent-Kaurane-16ß,17,19-triol-3-one (1), along with three known ent-kaurane diterpenoids (2-4) as ent-Kaurane-3α,16ß,17-triol (2)，ent-16S,17-dihydroxy-kaurane-3-one (3) and ent-3S,16S,17-trihydroxy-kaurane-2-one (4). Their structures were elucidated by extensive spectroscopic analyses including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. Compound 2 was a new natural product and firstly isolated from nature, while compounds (3-4) were isolated from E. stracheyi for the first time. All isolated compounds (1-4) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7 and SW-480).

The effect of early goal-directed therapy on mortality in patients with severe sepsis and septic shock: a meta-analysis.

BACKGROUND: The Surviving Sepsis Campaign has recommended early goal-directed therapy (EGDT) as an essential strategy to decrease mortality among patients with severe sepsis and septic shock. However, three latest multicenter trials failed to show its benefit in the patients with severe sepsis and septic shock. This article was to evaluate the effect of EGDT on the mortality of patients with severe sepsis and septic shock. METHODS: Relevant studies from PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were identified from January 1, 2001 to June 13, 2015. With both randomized controlled trials (RCTs) and non-RCTs selected, a meta-analysis on the effects of EGDT on all identified trials was performed. The primary outcome was the inhospital mortality. In subgroup, RCTs and non-RCTs were analyzed, respectively. RESULTS: A total of five RCTs and 10 non-RCTs involving 3285 patients in EGDT group and 3233 patients in the control group were identified. Pooled analyses of all studies showed significant difference in the inhospital mortality between the EGDT group and the control group (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.74-0.94; P = 0.003) with substantial heterogeneity (χ2 = 24.93, P = 0.04, I(2) = 44%). In subgroup analysis, there were no significant difference in inhospital mortality between the EGDT group and the control group (RR, 0.95; 95% CI, 0.83-1.10; P = 0.51) with no significant difference in heterogeneity (χ2 = 6.62, P = 0.16, I(2) = 40%) in RCTs. In non-RCTs, EGDT significantly reduced inhospital mortality (RR, 0.75; 95% CI, 0.65-0.88; P = 0.0003) with no significant difference in heterogeneity (χ2 = 11.96, P = 0.22, I(2) = 25%). CONCLUSIONS: This meta-analysis suggests that EGDT can significantly reduce the mortality among patients with severe sepsis and septic shock.

A new tigliane-type diterpene from Euphorbia dracunculoides Lam.

One new tigliane-type diterpene, 4-deoxy-4(ß)H-8-hydroperoxyphorbol-12-benzoate-13-isobutyrate (1), together with two known diterpenoids, 3-acetyl-5,8-dibenzoyl-14α-propanoyl-13,17-epoxy-7-myrsinaone diterpene with C9-C10 cyclised to form an additional lactone ring (2), Euphodendriane A (3) have been isolated from the whole plants of Euphorbia dracunculoides Lam. Their structures were elucidated by means of extensive spectroscopic analysis (NMR and HR-ESI-MS) and comparison with data reported in the literature. This is the first isolation of 8-hydroperoxy tigliane diterpene (1) from the genus of Euphorbia. All compounds were evaluated for their antifungal activities.

A rhodamine based fluorescent probe for Hg2+ and its application to cellular imaging.

A new rhodamine-based fluorescent probe (Rh-F) for detection of Hg(2+) ions was synthesized, which could bind Hg(2+) in aqueous ethanol (7:3, v/v) at pH 7.0 with detectable change in color and fluorescence. The response is based on a ring opening reaction and formation of a 1:1 complex, while ring-opening process of spirolactam enables large fluorescent enhancement and colorimetric change upon the addition of Hg(2+). The response is reversible and linear in the range between 200nM and 1000nM, with a detection limit of 4.2nM. Selectivity and competition experiments with various other metal ion revealed that Rh-F possesses highly selective fluorescent response to Hg(2+). Furthermore, the probe was successfully applied to fluorescent imaging of Hg(2+) in L-929 cells confirm that Rh-F can be used as a fluorescent probe for monitoring Hg(2+) in living cells.

A new rhodamine-based "off-on" fluorescent chemosensor for Hg (II) ion and its application in imaging Hg (II) in living cells.

A novel rhodamine derivative (Rh-C), synthesized by the reaction of rhodamine ethylenediamine and cinnamoyl chloride, was evaluated as a chemoselective Hg(2+) ion sensor. Addition of Hg(2+) to an ethanol aqueous solution of the Rh-C resulted in a color change from colorless to obvious pink color together with distinctive changes in UV-vis absorption spectrum and fluorescence spectrum. However, other common alkali-, alkaline earth-, transition- and rare earth metal ions induced no or minimal spectral changes. The interaction of Hg(2+) and sensor Rh-C was proven to adopt a 1:1 binding stoichiometry and the recognition process is reversible. The chemosensor displayed a linear response to Hg(2+) in the range of 0.4-5 µM with a detection limit of 7.4 × 10(-8) M. The sensor Rh-C was also successfully applied to the imaging of Hg(2+) in HL-7702 cells.

Isolation and identification of a novel WSSV nucleocapsid protein by cDNA phage display using an scFv antibody.

In a previous study, a scFv phage display library against white spot syndrome virus (WSSV) was constructed and yielded a clone designated A1 with conformational specificity against native but not denatured viral antigen. Although the clone A1 has been used successfully as a diagnostic antibody, its precise target antigen has not been elucidated. A different strategy was adopted involving the construction of a second T7 phage display library utilizing mRNA isolated from shrimp infected with WSSV. Following RT-PCR and T7 phage library construction, phages displaying the candidate epitope were selected with A1 scFv. Since successive enrichment steps were not associated with an increased titer of the phages, enrichment after successive tests was confirmed by PCR resulting in the preferred selection of a specific DNA sequence encoding a novel nucleocapsid protein WSSV388. Immune electron microscopy revealed that WSSV388 is located on the nucleocapsid. This result demonstrated that unknown antigen could be identified by phage display using the epitope conformation dependent scFv.