Bimetallic Ru/Ru-Catalyzed Asymmetric One-Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones.

Asymmetric sequential hydrogenations of α-methylene γ- or δ-keto carboxylic acids are established in one-pot using a bimetallic Ru/Ru catalyst system, achieving the stereodivergent synthesis of all four stereoisomers of both chiral γ- and δ-lactones with two non-vicinal carbon stereocenters in high yields (up to 99%) and with excellent stereoselectivities (up to >99% ee and >20:1 dr). The compatibility of the two chiral Ru catalyst systems is investigated in detail, and it is found that the basicity of the reaction system plays a key role in the sequential hydrogenation processes. The protocol can be performed on a gram-scale with a low catalyst loading (up to 11000 S/C) and the resulting products allow for many transformations, particularly for the synthesis of several key intermediates useful for the preparation of chiral drugs and natural products.

Cilostazol for Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, was reported to reduce cerebral vasospasm and improve outcomes. We aimed to conduct an updated systematic review and meta-analysis of the efficacy and safety of cilostazol in aSAH. METHODS: We systematically searched PubMed, Embase, MEDLINE, and the Cochrane Library for articles published in English with the latest publishing time in August 2020. Articles reporting favorable outcome as the primary outcome and reporting severe angiographic vasospasm (aVS), symptomatic vasospasm (sVS), new cerebral infarction, or mortality as the secondary outcome were included in this review. Furthermore, we examined whether clinical outcomes were associated with the dosage of cilostazol (300 mg/day vs. 100-200 mg/day). RESULTS: Data from 405 patients in 4 randomized controlled trials (RCTs) and 461 patients in 4 observational studies (OSs) were included. In RCT studies, cilostazol was associated with significant favorable outcomes at discharge or 1 month (risk ratio [RR] 1.41, 95% confidence interval [CI] 1.01-1.97, p = 0.04) or 3 or 6 months (RR 1.16, 95% CI 1.05-1.28, p = 0.002). However, in OSs, no significant difference was indicated in favorable outcomes at discharge or 1 month (RR 1.22, 95% CI 0.94-1.60, p = 0.14) nor 3 or 6 months (RR 1.29, 95% CI 0.92-1.81, p = 0.14). The analyses found that cilostazol significantly reduced the incidences of severe aVS (RCT: RR 0.64, 95% CI 0.41-1.01, p = 0.05; OS: RR 0.61, 95% CI 0.43-0.88, p = 0.007), sVS (RCT: RR 0.46, 95% CI 0.31-0.70, p = 0.0002; OS: RR 0.38, 95% CI 0.21-0.68, p = 0.001), and new cerebral infarction (RCT: RR 0.40, 95% CI 0.24-0.67, p = 0.0005; OS: RR 0.38, 95% CI 0.23-0.64, p = 0.0002). However, no significant difference in mortality (RCT: RR 0.86, 95% CI 0.23-3.21, p = 0.82; OS: RR 0.16, 95% CI 0.02-1.24, p = 0.08) was found. In 3 OSs which reported different doses of cilostazol (300 mg/day vs. 100-200 mg/day) for aSAH, the 300-mg/day cilostazol groups showed decreased delayed cerebral infarction (RR 0.27, 95% CI 0.09-0.81, p = 0.02) but no significant difference in shunt-dependent hydrocephalus (RR 0.92, 95% CI 0.33-2.60, p = 0.88) or functional outcomes (RR 1.14, 95% CI 0.74-1.75, p = 0.56) compared with the 100-200 mg/day cilostazol groups. CONCLUSIONS: The meta-analyses suggest the credible efficacy and safety of cilostazol in treating aSAH. Furthermore, 300-mg/day cilostazol treatment appeared to be more effective than 100-200 mg/day treatment.

[Irreducible Indirect Inguinal Hernia Caused by Sigmoid Colon Cancer Entering Right Groin:A Case Report].

We reported a case of irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.The patient complained about a right groin mass for more than 60 years with progressive enlargement for 3 years and pain for half a month.Abdominal CT examination at admission showed rectum and sigmoid colon hernia in the right inguinal area and thickening of sigmoid colon wall.Electronic colonoscopy and pathological diagnosis showed sigmoid colon cancer.Therefore,the result of preliminary diagnosis was irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.We converted laparoscopic exploration to laparotomy followed by radical sigmoidectomy and employed end-to-end anastomosis of descending colon and rectum in combination with repair of right inguinal hernia.The patient recovered well after operation and was discharged.

AgSbF6-Mediated Selective Thiolation and Selenylation at C-4 Position of Isoquinolin-1(2 H)-ones.

A new and facile AgSbF6-mediated protocol for the construction of C-4 thiolated or selenylated isoquinolin-1(2 H)-ones via a radical pathway was established. This reaction proceeded efficiently with excellent regioselectivity, a broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving thiyl radicals as key intermediates is proposed for the present transformation.

High tie versus low tie of the inferior mesenteric artery in colorectal cancer: A meta-analysis.

BACKGROUND: Colorectal cancer surgery includes "high tie" and "low tie"of the inferior mesenteric artery(IMA). However, different ligation level is closely related to the blood supply of anastomosis, which may increase the leakage rate, and it is unclear which technique confers a lower anastomotic leakage rate(AL) and survival advantage. OBJECTIVE: To compare the effectiveness and impact of inferior mesenteric artery (IMA) high ligation versus IMA low ligation on anastomotic leakage, lymph nodes yield rates and 5-year survival. METHODS: A list of these studies, published in English from 1990 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect and Web of Science. Anastomotic leakage rate, the yield of lymph nodes and 5-year survival were compared using Review Manager 5.3. RESULTS: There was no significant difference in anastomotic leakage, number of lymph nodes retrieved and 5-year survival rate for both techniques. CONCLUSIONS: Neither the high tie nor the low tie strategy has an evidence in terms of anastomotic leakage rate, harvested lymph nodes, and the 5-year survival rate. Further RCT is needed.

Novel HPPD inhibitors: triketone 2H-benzo[b][1,4]oxazin-3(4H)-one analogs.

BACKGROUND: Herbicides that inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) are very important for grass weed control. In order to discover novel HPPD herbicides, a series of triketone 2H-benzo[b] oxazin-3(4H)-one analogs was designed and synthesized. RESULTS: In comparison with the commercial triketone HPPD herbicide mesotrione (IC50 = 0.252 µM), some of these new triketone analogs displayed excellent HPPD inhibitory potency in vitro, for example B39 (IC50 = 0.172 µM) and B41 (IC50 = 0.156 µM). In addition, some of these compounds exhibited pre- and post-emergence herbicidal activity similar to mesotrione when applied at 375 g/ha. CONCLUSION: Many of the title compounds described in this paper could be important lead structures for the further development of novel HPPD herbicides. © 2017 Society of Chemical Industry.

Route to Substituted Furan-2(5H)-ones from cyclo-Alkenecarboxylic Acids and Acrylates via C-H Activation.

Under rhodium(III) catalysis, four kinds of cycloalkenecarboxylic acids successfully reacted with acrylates via direct activation of the ß-alkenyl C-H bond. The present protocol provides the facile and highly efficient synthesis of substituted furan-2(5H)-ones from readily available starting materials with moderate to good yields. In addition, their possible reaction mechanisms were also discussed.

Gender differences in colorectal cancer survival: A meta-analysis.

A meta-analysis was conducted to determine the influence of gender on overall survival (OS) and cancer-specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer-specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85-0.89) and CSS (HR = 0.92; 95% CI = 0.89-0.95) than males after meta-analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.

Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer: A meta-analysis.

The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ±â€Šcetuximab was compared. Data on clinical efficacy and safety were pooled and compared by ORs, HRs, and 95% CIs.Five eligible trials with 1464 patients were included in the meta-analysis. Compared to FOLFOX/FORFIRI, cetuximab as the first-line therapy has improved overall survival (OS) (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.72-0.93, P = 0.003), progression-free survival (PFS) (HR = 0.66, 95% CI: 0.56 -0.77, P < 0.00001), and overall response rate (ORR) (odds ratio [OR] = 2.12, 95% CI: 1.70-2.65, P < 0.00001). However, Grade 3/4 AE was increased with the OR of 2.76 (95%CI: 2.01-3.78, P < 0.00001). The most common grade 3/4 toxicity in the wild-type KRAS population was neutropenia and diarrhea. For cetuximab plus FOLFIRI, there was a higher incidence of grade 3 or 4 diarrhea (OR = 1.76, 95% CI: 1.15-2.70, P = 0.01), but there was no significant difference for neutropenia (OR = 1.35, 95% CI: 1.00-1.83, P = 0.05).The addition of cetuximab in mCRC as the first-line treatment is a potential effective approach in the improved outcomes but associated with increased toxicity.

Robotic gastrectomy versus open gastrectomy in the treatment of gastric cancer.

BACKGROUND: Robotic gastrectomy (RG) has been developed to improve surgical quality and to overcome the limitations of conventional open gastrectomy (OG) for gastric cancer. The aim of this meta-analysis is to comprehensively compare the safety and efficacy between robotic surgery and open surgery for treating gastric cancer. METHODS: Major databases were searched for retrospective case-matched studies comparing RG and OG for treating gastric cancer. A list of these studies, published in English from 1990 to 2016, was obtained independently by two reviewers from databases such as PubMed, MEDLINE, ScienceDirect, the China National Knowledge Infrastructure and Web of Science. Intraoperative data, oncological outcomes and postoperative complications were compared using Review Manager 5.3. RESULTS: Seven studies involving 5970 patients with 606 cases of RG and 5364 cases of OG were included in this meta-analysis. Compared to OG, RG has a significantly longer operation time [weighted mean differences (WMD) = 63.72, 95 % confidence interval (CI) 33.83-93.61, P < 0.0001], lower blood loss (WMD: -129.74, 95 % CI -178.31 to -81.16, P < 0.00001) and shorter hospital stay (WMD = -2.39, 95 % CI -2.92 to -1.87; P < 0.00001). No statistical difference was noted based on the rate of overall postoperative complication, wound infection, bleeding, ileus and obstruction, abdominal collections and abscesses, and the rate of anastomotic leak in the RG versus OG. Postoperative oncological outcomes showed that there were also no statistical differences among the number of retrieved lymph nodes, proximal resection margin, distal resection margin except for tumor size (WMD = -1.60; 95 % CI -2.96 to -0.25; P = 0.02). CONCLUSION: The results of this meta-analysis suggest that RG will be more accessible than conventional OG for gastric cancer. However, more prospective, well-designed, multicenter, randomized controlled trials are necessary to further evaluate the safety and efficacy as well as the long-term outcome of this technology.