Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

Objective:To explore the clinical application value of MRI in quantitative evaluation of anterior cruciate ligament mucoid degeneration (ACL-MD).Methods:From March to July 2020, 40 patients who were scheduled to undergo arthroscopic treatment were prospectively collected in the First Affiliated Hospital of Kunming Medical University.The anterior cruciate ligament tissue from the lateral edge of the tibial end was taken during the operation. Based on the pathologicalre sults, the patients were divided into the ACL-MD group ( n=19) and the normal group ( n=21). The sagittal plane three-dimensional steady-state rapid precession (3D-FIESTA), T 1 mapping, T 2 mapping, and T 2* mapping were performed before the knee joint surgery, and the scanned images were post-processed and analyzed to measure the T 1, T 2, and T 2* values of the tibial end of the anterior cruciate ligament.The relaxation time of the ACL-MD group and the normal group was compared using independent sample t test. The ROC curve was drawn using each parameter and the areas under the curve (AUC) for the diagnosis of ACL-MD were obtained.DeLong test was used to compare the differences of AUCs. Results:The T 1 [(1 291.9±273.4) ms], T 2 [(54.8±10.6) ms], and T 2* values [(30.6±6.4) ms] of anterior cruciate ligaments in the ACL-MD group were significantly higher than those in the normal group [ (1 087.0±121.0), (44.8±7.1), (20.4±4.8) ms; t=3.011, 3.473, 5.658, all P<0.001]. The AUCs of T 1, T 2, T 2* were 0.747, 0.764, 0.912, sensitivity of 63.2%, 63.2%, 100%, and the specificity of 100%, 95.2%, 76.2% in diagnosing ACL-MD. The AUC of the T 2* value was higher than those of the T 1 and T 2 values, and the differences were statistically significant ( Z=1.734, 2.162, P=0.043, 0.031). Conclusion:T 1, T 2, T 2*values measured by MRI quantitative imaging have high performance in assessing knee joint ACL-MD, and T 2* value has the largest AUC and the highest diagnostic efficiency.

Objective: To evaluate the efficacy of reinforcement on duodenal stump using single purse-string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods: A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux-en-Y or Billroth Ⅱ reconstruction and reinforcement on duodenal stump using laparoscopic single purse-string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty-three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux-en-Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse-string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3-0 single-strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien-Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results: All patients completed operations successfully. The mean time of laparoscopic single purse-string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery-related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non-surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re-operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien-Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse-string suture during laparoscopic radical gastrectomy with Roux-en-Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

Objective To evaluate the efficacy of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux?en?Y or BillrothⅡreconstruction and reinforcement on duodenal stump using laparoscopic single purse?string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty?three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux?en?Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3?0 single?strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien?Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results All patients completed operations successfully. The mean time of laparoscopic single purse?string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery?related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non?surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re?operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien?Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse?string suture during laparoscopic radical gastrectomy with Roux?en?Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

Objective To evaluate the efficacy of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux?en?Y or BillrothⅡreconstruction and reinforcement on duodenal stump using laparoscopic single purse?string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty?three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux?en?Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3?0 single?strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien?Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results All patients completed operations successfully. The mean time of laparoscopic single purse?string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery?related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non?surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re?operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien?Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse?string suture during laparoscopic radical gastrectomy with Roux?en?Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

The strategies for prevention and treatment of recent complications after radical gastrectomy should be of equal emphasis on both theory and technology.Systematic prevention is the fundamental strategy,and adequate preoperative assessment and preparation are the basis.A reasonable extension of the radical gastrectomy and standard and refined surgical procedures could reduce the occurrence of complications.In addition,identifying these complications timely and taking effective treatments promptly according to the clinical context are the keys to reducing the treatment cycle and decreasing the mortality.

Objective Retrospectively analysis on death cases related with aortic dissection provides support for further forensic investigation on such cases. Methods 44 Cases on aortic dissection are collected from the Forensic Medical Center in Kunming Medical University from 2002to2017.Statistic anaylisis was applied to each case's general information,clinical stage,clinical manifestation,risk factors,pathological type,rupture state,and direct case of death. Results The results showed that aortic dissection occurs moslty in middle age male who ranges from 40 to 49 years old. Most cases were aute aortic dissection, and the death rate was the highest in winter and the lowest in spring. Furthermore, pain is shown to be the most common symptom. Atherosclerosis is a critical factor that contributes to the occurance of aortic dissection. In general, type A aortic dissection occurs more frequently than type B. The rupture, located in ascending aorta, often is in a transverse shape. Cardiac tamponade is the primary cause of death.Conclusion Definite initial symptoms arises before aortic dissection rupture and always show many high-risk factors. It is beneficial to forensic identification of the relation between aortic dissection and injury or medical behavior should be considered carefully.

Background and purpose:Hepatitis B virus X protein (HBx) and hypoxia inducible factor-1α(HIF-1α) play key roles in hepatocarcinogenesis and the development of hepatocellular carcinoma. Positive correlation on the expression of these 2 proteins in hepatocellular carcinoma tissues has been found, whereas the underlying mechanisms have not been fully elucidated. This study focused on the role of HBx in regulating HIF-1α and the underlying mechanisms in hepatocellular carcinoma cells. Methods:The expression plasmids were transfected into Huh7 cells with LipofectemineTM 2000. Western blot analysis was applied to detect the expressions of HIF-1αand HIF-1β protein. The transcriptional activity of HIF-1α was detected by the commercial analysis kits. The mRNA levels of HIF-1αand its target genes, including vascular endothelial growth factor (VEGF) and multi-drug resistance gene 1 (MDR1), were detected by quantitative real-time PCR (qRT-PCR). Immunoprecipitation analysis was applied to detect the interaction of HIF-1α, HBx and protein von Hippel-Lindau (pVHL). Results:Huh7 cells transfected with HBx plasmid led to sharp increase of HIF-1αprotein and transcriptional activity, as well as the mRNA of VEGF and MDR1 (P<0.05). However, the mRNA level of HIF-1αwas not obviously changed after HBx transfection (P>0.05). Meanwhile, HBx also signiifcantly impaired the function of pVHL in mediating the degradation of HIF-1αby ubiquitin hydrolase. This finding was further confirmed by the immunoprecipitation analysis, which showed that HBx could directly bind to pVHL, but not to HIF-1α. Conclusion:HBx may inhibit the inter-activation between pVHL and HIF-1αthrough directly binding to pVHL, and thus enhance the stability and transcriptional activity of HIF-1α.

Objective:To investigate effects of tumor specific TCR gene Vα12.2-Vβ7.1 modification on recognition of tumor antigen and activation of anti-tumor reactivity of T cells.Methods: T cells were transduced using recombinant Ad 5F35-TRAV-TRBV adenovirus ,and multiplicity of infection was optimized.Specific lysis of T cells was evaluated by calcein release assay.The frequency of apoptotic cells in target cells was detected by Annexin V /PI double-labeled FACS.The expression of FasL on T cells was analyzed by FACS.The secretion of cytokine IFN-γand IL-2 of T cells was determined by ELISA assays.Results: The highest tranduce efficiency was obtained at MOI 100 by recombinant Ad5F35-TRAV-TRBV adenovirus.The frequency of TCRVα12+Vβ7+cells reached above 25%3 days after transduction.TCR gene modification enhanced the ability of T cells to lyse HLA-A2+AFP+target cells(P<0.001), the ability of T cells to induce HepG-2 apoptosis(P<0.001),and expression of FasL on T cells(P<0.001).TCR gene modification also enhanced T cells to secret IFN-γafter coculture with antigen positive tumor cells ( P<0.001 ).Conclusion: Specific TCR gene modification by recombinant adeno virus effectively promotes T cells to recognize antigen positive tumor cell and exert anti -tumor reac-tivity.