Colorectal cancer is a common malignant tumor of the digestive system. In recent years, with the changes in people's lifestyle, dietary structure, and the intensification of environmental pollution, the incidence of colorectal cancer in adolescents and young adults (AYAs) has significantly increased. AYAs refer to individuals aged 15 to 39, and compared with elderly cancer patients, AYAs with cancer have higher long-term and advanced-stage risks as well as worse prognosis, and colorectal cancer also become an important cause of death in AYAs. This study took colorectal cancer as a study point to analyze the risk factors and clinical characteristics of AYAs with colorectal cancer, explored the diagnosis and treatment methods for AYAs with colorectal cancer, and provided a basis for formulating prevention and control measures in clinical practice.

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; ErbB Receptors ; metabolism ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Apoptosis ; Autophagy ; Breast Neoplasms ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors ; Humans ; Phosphatidylinositol 3-Kinases ; Protein Kinase Inhibitors

Objective To investigate the effect of high expression of protein tyrosine phosphatase SHP-1 on the tumor cell invasiveness and chemosensitivity of esophageal squamous cell carcinoma.Methods EC9706 ceils of esophageal squamous cell carcinoma were divided into three groups:the blank group was not given any treatment;the experimental group used SHP-1 mimic instantaneous vector to transfect cells for 24 h,and used 10 μmol/L cisplatin to treat EC9706 cells for 12 h;the control group selected 10 μmol/L cisplatin to treat EC9706 cells for 12 h.Cell proliferation was detected by using methyl thiazolyl tetrazolium (MTT) assay,and cell invasion was detected by using Transwell chamber.The expression of SHP-1 mRNA was detected by using fluorescence quantitative polymerase chain reaction.The expression level of SHP-1 protein was detected by using Western blot.Results The expression of SHP-1 mRNA in the experimental group (3.42t0.14) was higher than that in the control group and the blank group (1.09±0.13,0.42±0.24,F =9.143,P ＜ 0.05).Compared with the control group and the blank group,the cell growth inhibition rate and the apoptosis index in the experimental group were increased (both P ＜ 0.05),and the differences between any two groups were also statistically significant (all P ＜ 0.05).The cell invasion rate in the experimental group,the control group and the blank group was (6.5±1.3) ％,(18.5±2.5) ％ and (45.2±7.2) ％,respectively,and the difference was statistically significant (F =11.853,P ＜ 0.05).Conclusion High expression of SHP-1 can inhibit the invasion of esophageal squamous cell carcinoma,improve chemosensitivity,promote apoptosis and inhibit cell proliferation,which could lay a theoretical foundation for improving the efficacy of chemotherapy for esophageal squamous cell carcinoma.

Objective To evaluate the clinic effect of reverse less invasive stabilization system (LISS) in treatment of femoral intertrochanteric fracture.Methods The study enrolled 22 cases of femoral intertrochanteric fractures treated with reverse LISS from January 2007 to January 2011.Twelve out of the cases were males and 10 were females,with age ranging from 44 to 86 years (mean,72.5 years).Left fracture occurred in 8 cases and right in 14 cases.Causes of injury included fall on the ground in 15 cases,vehicle accidents in 4 cases,and fall from height in 3 cases.There were 15 cases of type Ⅲ and 9 of type Ⅳ according to Evans-Jensen classification and all fractures were closed injuries.Time from injury to operation was 3-14 days (mean,5.3 days).Results Intraoperative hemorrhage was (130.5 ± 60) ml and operation time was (55 ± 15) min.All cases were followed up for 12-30 months (mean,14.8 months).Fracture healing time was 10-27 weeks (mean,13.4 weeks).Harris hip score was excellent in 11 cases,good in 8,fair in 2,and poor in 1,with excellent and good rate of 86％.Two cases felt greater trochanter pain at follow-up ; one presented with plate breakage and malunion at 6 months postoperatively,but may need no further treatment; the rest healed without complications of surgical site infection,varus deformity of the hip,implant breakage,fracture redisplacement,screw drawing pullout or cutout.Conclusion Reverse LISS plating is an effective treatment for femoral intertrochanteric fractures,but the procedure can not assure 100％ success.

Objective To investigate the clinical efficacy of locking compression plate fixation through a modified anterolateral approach for posterolateral tibial plateau fractures.Methods From June 2010 to March 2012,19 patients with posterolateral tibial plateau fractures underwent locking compression plate fixation through a modified anterolateral approach in our hospital.There were 11 males and 8 females,aged from 26 to 55 years (average,38.3 years).The injury causes included traffic accident in 10 cases,fall from height injury in 7 cases and falling injury in 2 cases.Two patients had avulsion fracture of the anterior cruciate ligament.The modified lateral S-shaped incision was adopted for all patients.All the patients underwent early and suitable rehabilitation after operation.The radiographic and clinical results were evaluated by using X-rays and the Rasmussen score,respectively.Results The average operative time was 95 minutes (range,80 to 120 minutes),and the average intraoperative blood loss was 180 ml (range,100 to 400 mi).All the patients were followed up for 12 to 24 months (average,16.2 months).Bone union was obtained in all patients,and the bony union time ranged from 8 to 14 weeks.There was no implant loosening/ breakage,bone nonunion,genu valgum,genu varum,redisplacement of fracture,and knee instability.Anatomic reduction was obtained in 18 patients.For one patient with posterolateral comminuted dislocation fracture,CT scan showed a step-off of 2 mm in joint surface after operation,and at final follow-up,the patient suffered from mild pain and the range of motion of the knee joint was 0 to 105 degree.The range of motion of the knee joint was 5 to 90 degree in one patient.The Rasmussen score ranged from 13 to 30 (average,22.9±4.9); the results were excellent in 10 cases,good in 7 cases and fair in 2 cases,and the excellent and good rate was 89.5％.Conclusion Locking compression plate fixation through a modified anterolateral approach is an effective method for posterolateral tibial plateau fractures,which has several advantages,such as simple and safe operation,stable fixation and less complications.

Objective To evaluate effects of minimally invasive dynamic hip screw(DHS)in treatment of intertrochanteric femoral fractures.Methods The study involved 98 patients with intertrochanteric femoral fractures treated by closed reduction and C-arm fluoroscopy guided minimally invasive DHS from January 2004 to January 2010.According to AO classification,there were 38 patients with type A1 fractures and 60 with type A2 fractures.According to Evans classification,there were nine patients with typeⅠ?fractures,29 with type Ⅱ,36 with typeⅢ?and 24 with type V.Intraoperative blood loss,operation time and incision length were recorded.Results The intraoperative hemorrhage,operation time and incision length were average 250 ml(range,150-450 ml),54.3 minutes(range,45-70 minutes),and 5.2 cm(range,4-7 cm),respectively.All the patients were followed up for 12-38 months(mean 16.8 months).Fracture healing time was 10-14 weeks(average 11.5 weeks).According to Zuekerman functional scoring for hip joint,the results were excellent in 61 patients,good in 30,fair in four and poor in three,with excellence rate of 92.9％.Varus deformity of hip occurred in four patients.No patient presented surgical site infection,implant failure or displacement of fractures.Conclusion Minimally invasive DHS is an effective means in treating intertrochanteric femoral fractures,but the key point of successful treatment is to strictly grasp the correct operative procedures.

ObjectiveTo discuss the clinical results of surgical reduction and fixation via posterolateral knee approach in the treatment of postemlateral tibial plateau fractures.MethodsThe study involved 32 patients with posterolateral tibial plateau fractures treated through posterolateral knee approaches from January 2006 to July 2009.There were 19 males and 13 females,at the age of 27-70 years (mean,38.1 years).Injury causes included traffic injuries in 19 patients,high fall injuries in nine and other in four.There were seven patients combined with anterior cruciate ligament injuries,which was all tibial plateau insertion avulsion. Results All patients were followed up for 12-36 months (mean,18.2 months),which showed bone union,without presence of incisional infection,loosening or breakage of screws,varus or valgus deformity of the knee,or fracture redisplacement.One patient had tension injury of common peroneal nerve postoperatively and recovered after two months conservative treatment of Methycobal.According to the Rasmussen knee function score,the results were excellent in 19 patients,good in 11 and fair in two,with excellence rate of 94％.ConclusionPosterolateral knee approach facilitates the reduction and fixation of posterolateral tibial plateau fractures and has advantages of clear exposure,convenient placement of internal fixation,small invasion and good clinical results.

Objective To discuss the operative procedures and clinical result of posteromedial and posterolateral approaches in treatment of posterior condylar tibial plateau fractures. Methods From January 2006 to June 2008, 21 patients of posterior condylar tibial plateau fractures were treated by posteromedial and posterolateral knee approaches. There were 12 males and 9 females. The age ranged from 28 to 68 years, with a mean of 39.5 years. Of the patients, 13 had resulted from a traffic accident and 8 had caused by a fall. As for the state of posterior condylar tibial plateau fractures, 7 patients had a medial condylar.fracture, 8 patients had a lateral condylar fracture and 6 patients had a bilateral condylar fracture. Results A follow-up lasted 12-24 months (mean 16.2 months ) in 21 patients. There was no infection, no varus or valgus of the knee, no nerve injuries and loosening or breakage of the screw. All cases had attained bone union. According to the Rasmussen functional scoring, the results were excellent in 12, good in 7 and fair in 2. The excellent and good rate of clinical results was 90.5%. Radiologic results were graded with the Rasmussen score to evaluate the reduction of fracture. There were excellent in 13, good in 7 and fair in 1. The excellent and good rate of clinical results was 95.2%. Conclusion Posteromedial and posterolateral approaches can facilitate the reduction and fixation for posterior condylar tibial plateau fractures. It has many advantages such as good exposure, less invasion and the excellent clinical results.

BACKGROUND: Due to good biocompatibility, autologous bone has been considered as the optimal graft, but its source is too limited to meet the clinical requirements. In addition, the harvesting of iliac bone is associated with significant morbidity, thus searching for a substitute material of autologous bone graft is a current topic of study.OBJECTIVE: To study the biocompatibility and osteogenesis capacity of autosolidifying calcium phosphate cement (CPC) in the repair of bone defects.DESIGN, TIME AND SETTING: A self-control observation was performed among 94 patients who were admitted at the Department of Orthopedics in Yiwu Central Hospital (Yiwu, Zhejiang, China) from February 2001 to September 2004.PARTICIPANTS: Ninety-four patients with bone defects were involved in this study. The underlying cause of bone defects was fracture collapse and reduction in 63 cases, osteomyelitis in 20 cases, bone cyst in 6 cases, fibrous dysplasia in 4 cases and enchondroma in 1 case. The area of bone defects ranged from 1cm×1cm to 4cm×20cm.METHODS: CPC was the product of Shanghai Rebone Biomaterials Co., Ltd (License N0. 2005-3460304, China). CPC powder was mixed with solidifying liquid according to the ratio of 3.0g: 1mL, and the filling dose of CPC was 3-42g. There were 74 cases implanted with pure CPC, including 38 cases with thoracolumbar fracture undergoing vertebroplasty, 25 cases with fracture undergoing open repair, and 11 cases underwent focal debridement of benign bone tumor. in another 20 cases of osteomyelitis, drug-loaded CPC was implanted.MAIN OUTCOME M[EASURES: After the CPC implantation, all patients were observed according to the following indexes: allergic or toxic reaction, rash or high fever, levels of serum calcium, phosphors and alkaline phosphatase. X-ray radiography at month 12 after implantation was employed to observe the osseointegration of the implanted CPC to host bone and the degradation of CPC.RESULTS: All 94 patients were followed up for 14 months, and 76 of them for 24 months, 47 of them for 36 months, and 36 of them for 48 months. CPC developed primary solidification in human body within 30 minutes. Neither allergic or toxic reaction nor rash or high fever were found in all patients. The levels of serum calcium, phosphors and alkaline phosphatase were noted to be normal. No case companied with the itching in incision. The radiological examination showed that. the implanted CPC was directly bonded to the bone at the interface, and the bone contour at the defect sites was completely or partly restored. Degeneration and new bone were formed in some of the patients. Incision oozing light yellow fluids occurred in 9 cases, the bacterial culture was detected as negative, and all wounds healed through dressing changes. In the 20 cases implanted with drug-loaded CPC, no cases experienced recurrence of osteomyelitis and CPC degeneration was not complete.CONCLUSION: With good biocompatibility, safety and few complications, CPC is a good substitute for autologous bone graft in the repair of bone defects, and drug-loaded CPC is a selective treatment for osteomyelitis.