Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Objective To investigate the clinical efficacy of Da Vinci robot-assisted radical resection for right colon cancer.Methods The retrospective cross-sectional study was conducted.The clinical data of 85 patients with right colon cancer who were admitted to the First Hospital Affiliated to Army Medical University from August 2013 to February 2019 were collected.There were 56 males and 29 females,aged from 29 to 84 years,with an average age of 60 years.All patients underwent Da Vinci robot-assisted radical resection of right colon cancer,named right hemicolon D3 + complete mesocolic excision,and received infection prevention and total parenteral nutrition treatment after surgery.According to clinical pathological staging of guideline issued by National Comprehensive Cancer Network,patients underwent postoperative chemotherapy within 1 year after surgery.Observation indicators:(1) treatment status;(2) postoperative pathological examination;(3) follow-up.Follow-up was conducted using outpatient examination,telephone interview and mail every 3 months within 1 year after surgery,every 6 months from 1 to 3 years after surgery,and once a year from 3 to 5 years after surgery up to March 2019.The postoperative tumor metastasis and survival of patients were obtained.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were expressed as absolute number.Survival rates were calculated using life-table method.Results (1) Treatment status:85 patients underwent Da Vinci robot-assisted right hemicolon D3 + complete mesocolic excision successfully.The operation time,volume of intraoperative blood loss,time for postoperative outof-bed activities,time to recovery of gastrointestinal function,time to liquid diet intake were (178±28) minutes,(85±33) mL,(2.9± 1.8) days,(3.1 ± 2.7) days,(3.9± 1.9) days,respectively.There was no perioperative death.Eleven patients had postoperative complications including 5 of anastomotic leakage,2 of anastomotic bleeding,2 of pulmonary infection,1 of gastric emptying disorder and 1 of incomplete intestinal obstruction;they were cured and discharged after conservative treatment.All the 85 patients received postoperative infection prevention and total parenteral nutrition support,including 64 receiving systemic intravenous chemotherapy with 6 -8 cycles of FOLFOX or XELOX,7 receiving 6-8 cycles of oral capecitabine,and 14 receiving no chemotherapy.(2) Postoperative pathological examination:the number of harvested lymph nodes was 20± 11 and 25 had lymph node metastasis.The length of proximal and distal cutting edge of the specimens was (16±5) cm and (9±5)cm,respectively.There was no cancerous cell on the cutting edge.High-differentiated adenocarcinoma,moderatedifferentiated adenocarcinoma,moderate-differentiated tubular adenocarcinoma,low-differentiated adenocarcinoma,mucinous adenocarcinoma,tubular combined with mucinous adenocarcinoma were detected in 2,40,14,16,9,4 patients,respectively.There were 8,28,24,5,12,8 patients in Ⅰ stage,Ⅱ A stage,Ⅱ B stage,Ⅱ C stage,ⅢB stage,Ⅲ C stage of TNM staging,respectively.(3) Follow-up:85 patients were followed up for 1-67 months,with a median follow-up time of 19 months.During the follow-up,1 of 85 patients had liver metastasis at 14 months after surgery and had survived after radiofrequency ablation treatment up to the end of follow-up.Three cases died of abdominal tumor metastases,1 of which in Ⅱ C stage died at 32 months after surgery,1 in Ⅲ B stage died at 4 months after surgery and 1 in Ⅲ B stage died at 16 months after surgery.The 1-,3-year overall survival rates were 97.1％ and 94.0％,respectively.Conclusion Da Vinci robot-assisted radical resection of right colon cancer is safe and feasible,with good short-and long-term outcomes.

Objective To compare the proximal femoral locking plate (LPFP) and proximal femoral intramedullary nail-spiral blade (PFNA) in minimally invasive internal fixation for elderly patients with intertrochanteric fractures.Methods One hundred and thirty patients aged over 60 years with intertrochanteric fractures were treated with minimally invasive internal fixation from January 2010 to June 2013,among them LPFP was applied in 69 cases and PFNA in 61 cases.The operation time,the numbers of intraoperative X-ray fluoroscopy,intraoperative blood loss,postoperative flow and decreased postoperative hemoglobin,postoperative complications,medical expenses,fracture healing time,postoperative hip Hariss function score were documented and compared between two groups.Results There were no significant differences in intraoperative blood loss [(132 ± 95) and (110 ± 79) ml],postoperative draining [(44 ± 16) and (41 ± 17) ml],decreased postoperative hemoglobin,fracture healing time [(10.5 ± 1.0) and (10.4 ± 1.5) weeks] and postoperative hip Hariss function score (87 ± 10 and 90 ± 8) between two groups.In LPFP group the number of intraoperative X-ray fluoroscopy (8.1 ±0.8 and 8.6 ± 0.9),hospitalization expenses,postoperative complications (7/69 and 16/61) were less than those in PFNA group (P＜0.05 or 0.01),however,the operation time was longer (P＜0.01).Conclusion LPFP may be a better choice in internal fixation for elderly patients with intertrochanteric fractures.

Objective To investigate the curative effects of the traditional surgical method of posterior pedicle Schanz screw fixa-tion with partially stripping injured paravertebral muscle in treating thoracolumbar fracture .Methods 52 cases with thoracolumbar fracture underwent posterior pedicle Schanz screw fixation to partially strip injured paravertebral muscle from January ,2010 to Jan-uary ,2012 .The patients were divided into partially stripping injured paravertebral muscle group (32 cases) and traditionally strip-ping injured paravertebral muscle group(20 cases) .The blood loss ,postoperative drainage ,kyphosis postoperative 3 d VAS scores , vertebral height correction rate ,Cobb angle correction ,Oswestry dysfunction indexes were copmared .Results Comparing with tra-ditionally stripping injured paravertebral muscle group ,the partially stripping injured paravertebral muscle group has better effect in transperative blood loss ,postoperative drainage and postoperative 3 d VAS scores ,the differences were statistically significant .But there was no statistical significance between the two groups in vertebral height correction rate ,kyphosis Cobb angle correction ,Os-westry dysfunction indexes .Conclusion Partially strip injured paravertebral muscle has less painful than traditional surgery does , being safe and effective with small invasion and easy to recover .

Objective To investigate the clinical efficiency,safety,adverse reactions and healthrelated life quality of transdermal fentanyl patches for pain management in terminal cancer patients with hepatic and renal dysfunction and ascites.Methods 98 terminal cancer patients with moderate to serve pain combined with abnormal hepatic and renal dysfunction were randomly divided into two groups.Group Ⅰ (n=56)received transdermal fentany patches.Group Ⅱ,the control group (n=42),received morphine controlledrelease tablets.Terms of pain intensity,function of renal and liver,adverse reactions and heath-related quality of life were assessed before and after treatment.Results Patients were satisfied with their pain management in both groups,and no significant difference in pain release was observed between the groups (x2 =0.01,0.07,0.01,0.04,P ＞ 0.05).The incidences of constipation and dysuresia were significantly less in the group Ⅰ compared with that of the group Ⅱ (x2 =7.32,3.96,P ＜ 0.05).The incidences of hypersomnia,dizzy,nausea and vomiting were similar betwecn the two groups (x2 =0.12,0.54,0.54,0.02,P ＞ 0.05).Most of the adverse reactions would relieve or disappear after symptomatic treatment.Values of BUN,CR,ALT,AST were similar before and after treatment in group Ⅰ (t =1.43,1.67,0.91,0.11,P＞ 0.05).However,in group Ⅱ,these values were significantly increased after treatment (t =17.59,49.17,42.12,36.23,P ＜ 0.05).The heathrelated life quality (appetite,spirit,somnus,fatigue,daily life and countenance) were significantly improved after treatment in both groups (the group Ⅰ t =3.37,4.40,2.07,5.66,4.48,P ＜ 0.05; the group Ⅱ t =2.03,2.27,3.59,4.16,2.79,P ＜ 0.05),the spirit group Ⅰ improved more obviously compared with group Ⅱ (t =2.93,P ＜ 0.05).Conclusion Transdermal fentanyl patches provides equal pain relief compared with Morphine controlled-release tablets in the terminal cancer patients with abnormal hepatic and renal function and ascites.Transdermal fentanyl patches significantly improve health-related quality with less hepatic and renal function influence and low incidence of adverse reaction.It should be recommended in the treatment terminal cancer patients with moderate to serve pain combined with abnormal hepatic and renal function and ascites.

Objective To investigate the clinical outcomes of sternoclavicular hook plate in treatment of the anterior sternoclavicular joint dislocation. Methods A new device named sternoclavicular hook plate was devised by our team. Between May 2002 and Octorber 2009, 66 patients with sternoclavicular joint anterior dislocation were treated with the new device, among whom there were 47 males and 19 females,aged 21-68 years old (average, 32.6 years old). Twenty-one cases were caused by crush injury, 5 cases by falling and 40 cases by traffic accident. Anterior fracture-dislocation was found in 41 cases. According to the Allman system, there were 35 cases of type Ⅱ and 31 cases of type Ⅲ. Patients were evaluated with serial clinical and radiographic examinations. Rockwood score were used after the operation to assess the curative effect. Results The average operative time was 33 min (range, 20-48 min). The mean blood loss was 60 ml (range, 20-90 ml). There were no vascular or peripheral nerve injuries in the patients. All incisions healed smoothly. The X-ray and CT showed that the reduction of sternoclavicular joint and the location of internal fixation were satisfactory. All the 66 patients were followed up for 12-37 months (average, 17 months). There was no internal fixation failure, redislocation or other complications. The sternoclavicular hook plate was removed 12 months after operation. The mean Rockwood's score was 13.2 (8 to 15). There were excellent in 50cases, good in 15 cases, and fair in 1 case. Conclusion The sternoclavicular hook plate is a new, safe and liable technique for sternoclavicular fracture-dislocation. This new technique is helpful for early functional exercises.

Objective To explore the efficacy of laparoscopy-assisted radical gastrectomy for patients with gastric cancer. Methods The clinical data of 726 patients who received laparoscopy-assisted radical gastrectomy for gastric cancer at the Southwest Hospital from January 2004 to April 2010 were retrospectively analyzed. The operation time, operative blood loss, number of lymph nodes dissected, length of hospital stay and mobidity were evaluated using t test or chi-square test. The survival of the patients were evaluated by Kaplan-Meier method.Results Laparoscopy-assisted radical gastrectomy was successfully carried out on 707 patients, and 19 patients were converted to open surgery. The mean operation time, operative blood loss, number of lymph nodes dissected were (179 ±52)minutes, (87 ±51) ml and 33 ± 14, respectively. The average distances of proximal and distal resection margin to the tumors were (6.3 ± 1.9)cm and (5.6 ± 1.7)cm, respectively. The average time to flatus, time to fluid diet and length of hospital stay were (2.9 ± 1.4) days, (3.1 ± 1.7) days and (7.9 ± 3.5) days,respectively. The peri- and postoperative mobidities were 2.2% (16/726) and 4.0% (29/726), respectively. A total of 685 patients were followed up for 6-82 months (mean, 48.3 months), and the 5-year survival rate was 58.4%. Conclusions Laparoscopy-assisted radical gastrectomy is a feasible procedure with minimal trauma, low morbidity and quick recovery of patients.

ObjectiveTo investigate the effect ofpinacidil hyperpolarizaed arrest on p38 mitogen-activited protein kinase (p38MAPK) during myocardial ischemia-reperfusion (I/R) in isolated rat hearts.MethodsFortyeight male SD rats weighting 250-300 g were randomly divided into 6 groups( n =8 each): natural arrest group (group A) ; St.Thomas group (group B) ; pinacidil hyperpolarization arrest group (group C) ;5-hydroxydecanoate (5-HD) group (group D);HMR-1098 group(group E) and 5-HD + HMR-1098 group(group F).Langendorff reperfusion model was established and K-H solution was retrogradely perfused for 15 min.In group A the hearts were arrested naturally afar perfusion was stopped; in group B St.Thomas solution was perfused; in group C pinacidil hyperpolarization solution was perfused; in the other three groups,K-H solution was perfused to isolated rat hearts for 10 min followed by 5 min 5-HD (group D) or HMR-1098(group E) or 5-HD and HMR-1098(group F) perfusion,then hyperpolarization arrest solution was given in each group.Each hearts suffered 60 min ischemia after arrest followed by 30 min K-H solution reperfusion.Coronary flow(CF),HR,left ventricular developed pressure( LVDP),left ventricular systolic pressure(LVSP) and the maximum rate of pressure rise (dp/dtmax) were measured at the end of 15 min K-H solution perfusion and at 20 min of reperfusion.Myocardial phosphatic and nonphosphatic p38MAPK expression was determined by Western blot at 30 min of reperfusion.ResultsCompared with group C,CF,HR,LVDP,LVSP and dp/dtmax were significantly decreased at 20 min of reperfusion and phosphatic p38MAPK expression was down-regulated,non-phosphatic p38MAPK expression was up-regulated at 30 min of reperfusion in groups A,B,D,E and F (P ＜ 0.05).Compared with group E,CF,HR,LVDP,LVSP and dp/ dtmax were significantly decreased at 20 min of reperfusion and phosphatic p38MAPK expression was down-regulated,non-phosphatic p38MAPK expression was up-regulated at 30 min of reperfusion in groups D and F ( P ＜0.05).ConclusionHyperpolarized arrest induced by pinacidil can improve cardiac function following myocardial I/R injury by up-regulating phosphatic p38MAPK expression,down-regulating non-phosphatic p38 MAPK expression and mitochondrial potassium channel is more important than membranous one during the regulation of phosphatic p38MAPK expression.