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.

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.

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.

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.

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).

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.