1.Effect contrast of thoracoscopic surgery and conventional thoracotomy lobectomy for esophageal carcinoma
Chongqing Medicine 2014;(14):1727-1728,1731
Objective To detect the contrast of vido‐assisted thoracic surgery (VATS) and conventional thoracotomy lobectomy for esophageal carcinoma .Methods 30 cases advanced esophageal carcinoma were selected in our hospital and divided into VATS group and thoracotomy group ,recorded pathological diagnosis ,operation and postoperative hospital stay and complications .Results VATS group had less bleeding ,shorter postoperative hospital stay ,less complications ,there was significant differences compared with thoracotomy group .Conclusion VATS in the treatment of advanced esophageal carcinoma have high safety ,definite curative effect ,and is worthy of extensive research and extension.
3.Development of fluorine-substituted NH2-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors: Boosting the safety and metabolic stability.
Xin JIN ; Shuai WANG ; Limin ZHAO ; Wenjuan HUANG ; Yinxiang ZHANG ; Christophe PANNECOUQUE ; Erik DE CLERCQ ; Ge MENG ; Huri PIAO ; Fener CHEN
Acta Pharmaceutica Sinica B 2023;13(3):1192-1203
Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC50 = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t 1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC50 = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH2-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC50 = 1.8-349 nmol/L). The best compound 5t in this collection (EC50 = 1.8 nmol/L, CC50 = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t 1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t 1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.