Objective To observe the clinical efficiency and safety of docetaxel(TXT) or irinotecan(CPT-11) combined with oxaliplatin(L-OHP) and S-1 in the treatment of advanced gastric cancer.Methods Totally 62 cases of patients with stage Ⅲ B-Ⅳ advanced gastric cancer in the Department of Gastrointestinal Surgery of our hospital were collected from 1st January 2010 to 1st March 2016,and were divided into two groups:TXT combined with L-OHP and S-1 group (modified DCF group,33 patients) and CPT-11 combined with L-OHP and S-1 group (modified ICF group,29 patients).All patients in the two groups were completed at least 1 cycle of chemotherapy until disease progression or intolerable toxicity.At the end of chemotherapy,the curative effects,untoward reactions and effects of surgery after neoadjuvant chemotherapy treatment were compared and analyzed.Results The objective response rate (ORR) in the modified DCF group(60.6％) was higher than that in the modified ICF group (51.7％),while no statistically significant difference was found in short-term effects between the two groups (Z=-0.837,P=0.403).There was no statistically significant difference in the incidences of main untoward reactions,including gastrointestinal reaction,myelosuppression,neurotoxicity,alopecia and liver function abnormal,between the two groups (P＞0.05).The radical resection rate of the modified DCF group and the modified ICF group after neoadjuvant chemotherapy was 66.7 ％ and 62.1 ％ respectively,the difference between the two groups was not statistically significant (x2=0.143,P=0.706).After neoadjuvant chemotherapy,the main postoperative complications were anastomotic leakage,anastomotic obstruction,abdominal infection,pulmonary infection,incision infection and gastric motility disorder,and no statistically significant difference was found in the incidence of postoperative complications between the two groups (P＞0.05).The was no statistically significant difference in quality of life after chemotherapy between the two groups (P＞0.05).Conclusion TXT or CPT-11 combined with L-OHP and S-1 has similar efficacy in the treatment of advanced gastric cancer,which could reduce tumour size,improve radical resection rate.Furthermore,untoward reactions of the two neoadjuvant chemotherapy protocols are almost the same,and can be tolerated.It is worthy of further research and application.

Objective To compare iso-osmolar iodixanol and low-osmolar iohexol for the incidence of contrast- induced nephropathy(CIN) in patients with chronic congestive heart failure undergoing coronary interventional therapy. Methods The study included 220 consecutive patients with chronic congestive heart failure and undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI) bewteen Janurary 2015 and May 2016. Study participants were divided into two groups by random digits table:iso-osmolar group (110 patients) and low-osmolar group (110 patients). The patients in iso-osmolar group were given iodixanol, and the patients in low-osmolar group were given iohexol. Serum creatinine (SCr), glomerular filtration rate (GFR) and cystatin C (CysC) were detected before the procedure and on the first, third day after the procedure. Then, the incidence of contrast-induced nephropathy (CIN) in two groups within 72 h of the procedure were observed and compared. Results The levels of SCr, GFR, CysC before operation had no significant differences (P>0.05). The levels of SCr in two groups on the first day after operation were increased, but there was no significant difference between two groups (P>0.05). On the first day after operation, the level of GFR in iso-osmolar group was higher than that in low-osmolar group, the level of CysC in iso-osmolar group was lower than that in low-osmolar group, and there were significant differences (P<0.05). On the third day after operation, the level of GFR in iso-osmolar group was higher than that in low-osmolar group, the level of CysC in iso-osmolar group was lower than that in low-osmolar group, and there were significant differences (P<0.01). The overall incidence of CIN was 20.9%(46/220). The incidence of CIN in low-osmolar group was 29.1%(32/110), in iso-osmolar group was 12.7%(14/110), and there was significant difference (P<0.05). Conclusions In chronic congestive heart failure patients undergoing coronary interventional therapy, the iso-osmolar contrast iodixanol is associated with a lower incidence of CIN compared with low-osmolar iohexol.

AIM: To investigate the impact of scavenger receptor class A type Ⅰ/Ⅱ (SR-A Ⅰ/Ⅱ) on the lipid metabolism in SR-A Ⅰ/Ⅱ gene deficient mice. METHODS: A probe of 660 bp fragment of SR-A Ⅰ/Ⅱ cDNA digested with PstⅠ and XhoⅠ from plasmid 122 was used to identify whether SR-A Ⅰ/Ⅱ had been knocked out in the tail DNA of the mutant (SR-/-) and control (SR+/+) mice by the method of Southern-blot analysis. The serum levels of triglycerides(TG), cholesterol(CH), low density lipoprotein(LDL), high density lipoprotein (HDL), apolipoprotein (Apo) A and ApoB of the mice fed with normal food and higher lipid food respectively were tested by biochemical method. RESULTS: The serum levels of LDL and body weights of group with SR-A Ⅰ/Ⅱ gene knocked out were higher than that of control group ( P

The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. To date, three selective CDK4/6 inhibitors have received approval from the U.S. Food and Drug Administration (FDA), and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers. In this perspective, we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells, analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment, review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds, explain the mechanisms associated with CDK4/6 inhibitor resistance and describe solutions to overcome this issue, and briefly introduce proteolysis targeting chimera (PROTAC), a new and revolutionary technique used to degrade CDK4/6.

Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft

Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.
AMP-Activated Protein Kinases ; metabolism ; Animals ; Antioxidants ; pharmacology ; Autophagy ; drug effects ; Cells, Cultured ; Endothelial Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Resveratrol ; pharmacology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism

Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.