Myeloid cell leukemia-1 (MCL-1) protein is one of the key antiapoptotic protein members of the B-cell lymphoma-2 protein family. Overexpression of MCL-1 is closely related to not only tumor progression but also resistance to targeted therapy and traditional chemotherapeutic drug. MCL-1 and its inhibitors have been studied in recent years. The mimetics of MCL-1 endogenous ligand BH3 have resulted in significant breakthroughs. In this study, the research progress on MCL-1 and its inhibitors in hematological malignan-cies is reviewed.

Objective:This study aimed to investigate the effects and the molecular mechanism of JNJ-7706621 on cell cycle and apoptosis of breast cancer cell lines. Methods:Breast cancer cell lines T47D and MDA-MB-231 were cultured in vitro and treated with JNJ-7706621 at varying concentrations. MTT assay was used to measure cell proliferation. Flow cytometry was applied to analyze the distribution of cell cycle and apoptotic rates. Western blot was performed to analyze the expression of cyclin B1-CDK, the phosphoryla-tion levels of CDK1Thr161 and CDK1Tyr15, as well as the expression of p53, Bcl-2, caspase3 and poly(ADP-ribose) polymerase (PARP). Results:JNJ-7706621 inhibited the proliferation of the T47D and MDA-MB-231 cells in a dose-and time-dependent manner. Flow cytometry showed that the T47D and the MDA-MB-231 cells in the G2/M-phase significantly increased after treatment at varying concentrations (0, 1, 2, 4μM) of JNJ-7706621:the G2/M-phase rates at the corresponding concentrations were (12.66±1.55)%, (20.63± 1.32)%, (23.20±1.82)%, and (32.19±2.37)%, respectively, for the T47D cells (P<0.05), and the G2/M-phase rates were (16.22±1.48)%, (21.45±0.85)%, (25.25±1.26)%, and (31.08±1.16)%, respectively, for the MDA-MB-231 cells (P<0.05). The rates of apoptotic cells were also significantly increased (P<0.05). Western blot results indicated that JNJ-7706621 exerted a slight effect on the expression of CDK1 and p53 and that the phosphorylation level of CDK1 decreased at the Thr161 site but increased at the Tyr15 site. In addition, cleaved caspase3 and PARP increased, whereas Bcl-2 and cyclinB1 decreased significantly. Conclusion:JNJ-7706621 can significantly inhibit the proliferation of breast cancer cell lines T47D and MDA-MB-231 by inducing cell cycle arrest and apoptosis, which may be associated with the downregulation of the CDK1 phosphorylation at the Thr161 site.

Carbon monoxide(CO)has a significant anti-inflammatory action.Carbon monoxide releasing molecule(CORM),as a new donor of CO,is used widely in biological study.The article reviewed the antiinflammatory action of CO and the progress of CORM.

Pancreatic cancer is a common disease with a poor prognosis. Despite recent advance in the field of diagnos-tic technique, surgical resection and adjuvant therapy for pan-creatic cancer, the overall 5-year survival rate is still less than 5%. This is due to its aggressive growth behavior, early local invasion and metastasis, and resistance to chemotherapy and radiation therapy. Surgical treatment is still regard as the only chance for curing pancreatic cancer. Many new strategies in the surgical treatment of pancreatic cancer, including extended lymphadeneetomy, vascular resection, the use of laparoscopy, surgery for metastastic or recurrent disease, and neoadjuvant therapy, are currently under debate. In this review, we discuss the current status of surgical treatment for pancreatic cancer, and highlight the controversies and focus.

0.05).Conclusions This study shows that in severe acute biliary pancreatitis patiens with biliary tract obstruction, emergency endoscopic therapy should be performed within 48 hours from the onset of symptoms; patients with mild acute biliary pancreatitis shoud also undergo prompt endoscopic therapy after ineffective conservative management or appearance of symptoms of acute biliary tract infection.

The pancreas located behind the peritoneum is a parenchymatous organ with a deep anatomical position and the surgical procedure for pancreatic diseases is complicated.And the pancreaticoduodenectomy (PD) is the most challenging operation in the field of pancreatic surgery even the abdominal surgery due to its large extent of resection and complexity of digestive tract reconstruction.Surgeons should select the most reasonable reconstruction methods on the basis of specific operative situation and surgical proficiency in order to ensure the quality of PD as well as prevent the postoperative complications.

Pancreatic cancer is regarded as high malignant neoplasm and surgical resection is considered as the only efficient therapeutic method.Radical surgery includes not only removing the whole carcinoma,but also resecting lymph nodes efficiently.There exist controversies whether extended lymphadenectomy can improve the overall survival of patients currently.We have analyzed and reflected on the controversies on the basis of overseas and domestic research status and our experience.

Objective To explore the effects of early postnatal nutrition on adult-onset insulin resistance by an artificial nutrition intervention during the critical period. Methods On postnatal day 2, Sprague-Dawley rats were assigned randomly to overnutrition (SL), normonutrition (NL) and undernutrition (LL) via artificially adjusting the number of pups nursed per dam. Litter size was adjusted to 3 pups/dam, 10 pups/dam and 20 pups/dam for the SL, NL and LL groups, respectively. There were eight litters for each group. All the pups were nursed by their natural dams and fed with a standard rodent laboratory chow. The pups were weaned on postnatal day 21 and three male pups from each litter were separated. After that, all male rats were housed three per cage and fed standard chow until 16 weeks old. At 3 and 16 weeks, rats were killed after overnight fasting and blood was collected. Liver, gastrocnemius muscle and perirenal and epididymal fat pads were dissected and weighed to calculate relative mass after normalization for body weight. Physiological parameters, biochemical values and insulin resistance status, including serum insulin level, homeostasis model assessment for insulin resistance (HOMA-IR) index and intraperitoneal glucose tolerance test (IPGTT), were dynamically monitored. Analysis of variance was used for statistical analysis. Results (1) Before weaning, the body weights of SL rats were significantly heavier than NL rats after postnatal day 10, and weights of LL rats were significantly lower than NL rats after postnatal day 7. After weaning, body weights of SL rats still remained heavier and weights of LL rats continued to be lower than NL rats (P<0.05). (2) At 3 weeks, the weights of liver and perirenal and epididymal fat pads in SL rats were significantly heavier than NL rats, whereas LL rats were lower than NL rats (P<0.05). At 16 weeks, the weights of liver, epididymal fat pads and gastrocnemius muscle in SL rats were significantly heavier than NL rats. Meanwhile, the weights of all detected tissues in LL rats were lower than the NL group. The weights of epididymal fat pads after normalization for body weight in the SL group were heavier than the NL group (P<0.05). (3) At 3 weeks, the fasting serum glucose level of the SL group was significantly higher than the NL and LL groups [(7.77±1.10) vs (6.33±1.20) and (5.80±1.51) mmol/L, respectively, F=13.217, P<0.01]. At 16 weeks of age, the serum insulin level in SL rats significantly increased compared to NL and LL rats [(0.31±0.11) vs (0.16±0.08) and (0.14±0.11) ng/ml, respectively, F=5.369, P=0.017]. For HOMA-IR evaluation, the index was significantly lower in LL rats compared to NL and LL rats at 3 weeks of age [(0.09±0.01) vs (0.25±0.01) and (0.31±0.05), respectively, F=25.923, P=0.005]. At 16 weeks, the index was significantly elevated in SL rats compared to NL and LL rats [(1.77±0.53) vs (0.84±0.44) and (0.83±0.67), respectively, F=5.765, P=0.015]. Furthermore, IPGTT was performed in all groups at 14 weeks of age. SL rats had significantly higher serum glucose levels at 60 min and a significantly increased area under the curve when compared to NL and LL rats (all P<0.05). (4) Serum from 16 week old SL rats was found to contain significantly higher levels of albumin, triglycerides and free fatty acids compared to NL rats (all P<0.05). Conclusions Early postnatal overnutrition induces persistent overweight and visceral white adipose accumulation in rats, while early postnatal undernutrition show the opposite effects. Early postnatal overnutrition may lead to adult-onset insulin resistance in rats. Avoiding overnutrition during the early postnatal period, a critical window for growth and development, may prevent or decrease later metabolic risks.

Severe acute pancreatitis presents high rate of postoperative complications and results in higher mortality.The main postoperative complications include bleeding,digestive tract fistula,residual infection in the abdominal cavity and retroperitoneum.Along with further deep understanding of the disease and the great changesof treatment,we have new insight for preventing and dealing with the postoperative complications.The damage control surgery combined with minimally invasive surgery concept and individual therapic mode make great effect for the management of postoperative complications.In this review,we focus on the therapies for postoperative complications of severe acute pancreatitis.

With the characteristics of complicated etiologic factors,multiple complications and high mortality,severe acute pancreatitis (SAP) has been treated by all kinds of clinical management.Management of SAP is a hot topic in recent decades.Researches on the pathophysiology of SAP have advanced dramatically during the past 20 years.As the number of randomized controlled studies of SAP has steadily increased,mainly in the United States and Europe,evidence based management was demanded for the management of SAP.The main improvement of the treatment results was achieved following internationally accepted recommendations; however,some aspects of the management are different and need to be discussed.There has been no consensus regarding the treatment of SAP.Failure to provide definitive treatment may potentially put a patient at risk of a fatal episode of SAP.The aims of this study,therefore,were to survey the currently adopted practice of the management of SAP,to evaluate the impact of various subspecialty interests on the practice adopted,and to suggest pathways towards a better implementation of the guidelines and other evidence-based management approaches.