Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Objective: To investigate the relevant prognostic factors of liposarcoma (LPS). Methods: The data of 78 patients with LPS treated in our hospital from July 2009 to March 2017 were reviewed. The 78 patients included 41 males and 37 females, and the average age was (60.5 ±13.4) years (ranged from 18 to 85 years). Among the 78 LPS patients, 27 were well-differentiated LPS, 13 were myxoid LPS, 35 were dedifferentiated LPS and 3 were pleomorphic LPS.The distribution of lesion location included 40 cases of extremities and 38 cases of retroperitoneal. 21 cases were treated with radical excision, 57 cases were treated with marginal resection. 7 patients were treated with postoperative radiotherapy and 9 patients with postoperative chemotherapy. Progression free survival (PFS) and overall survival (OS) of LPS patients were analyzed as clinical outcomes. Prognostic factors were analyzed by univariate and multivariate analyses. Results: 43 patients had local recurrence (9 of extremities/ 34 of retroperitoneal), 18 patients with metastasis (4 of extremities/ 14 of retroperitoneal). The 5-year PFS rate was 31.4% and 5-year OS rate was 44.3%. Univariate analysis showed that the histological subtype and the tumor location were related with PFS (P<0.05), while the histological subtype, the tumor location, the tumor size, the recurrence and metastasis were related with OS (P<0.05). Multivariate cox regression analysis showed that the tumor location was the independent prognostic factor of PFS (P<0.05), while the histological subtype and metastasis were the independent prognostic factors of OS (P<0.05). The median PFS of patients with myxoid LPS treated with radiotherapy was 34.6 months, which was significantly longer than 28.3 months of myxoid LPS patients without radiotherapy (P<0.05). Conclusions The tumor location is an independent prognostic factor of PFS in LPS patients.Retroperitoneal LPS is more prone to relapse and metastasize. OS is affected by pathological subtype and metastasis. Radiotherapy can improve the PFS of patients with myxoid LPS.

Objective: To investigate the assessment and treatment strategy of patients with renal cell carcinoma. Methods: The clinical data of 43 patients with renal cell carcinoma and bone metastases admitted to the First Affiliated Hospital of Nanjing Medical University from January 2006 to December 2018 were retrospectively analyzed. The follow-up time was 6 years, with an average age of 55.4 years (21-87 years). There were 29 males, 14 females, 22 cases of limb bone metastasis, 12 cases of spinal metastasis, 9 cases of multiple bone metastasis, 21 cases of Fuhrman grade 1 and 2, 19 cases of T₁, and 20 cases of N₀. All patients were confirmed by postoperative pathological examination or imaging data suggesting that bone metastasis are from renal cell carcinoma. Forty-three patients underwent primary renal surgery, and molecular targeted therapy was used after the operation. The treatment process was smooth, no obvious discomfort, and postoperative pathology showed clear cell carcinoma.22 patients with limb bones metastasis and 12 patients with spinal metastasis included in the study all met the indications for secondary surgery after the disease assessment. After communicating with the patient, 13 patients with limbs metastasis and 6 patients with spinal metastasis received local treatment, including complete resection of the extremities and spinal fixation, the remaining 15 patients and 9 patients with multiple bone metastasis were treated conservatively. There were 19 patients in the local treatment group, 13 patients with limbs bone metastasis, 6 patients with spinal bone metastasis, the average age was 54.9 years, the average diameter of the primary tumor was 4.7 cm. There were 24 patients in the conservative treatment group, 9 patients with limbs metastasis, 6 patients with spinal metastases and 9 cases with multiple bone metastasis, with an average age of 56 years and a primary tumor diameter of 5.6 cm. Limb metastatic lesions were evaluated according to the patient's general condition, bone pain, fracture risk, and bone metastasis. Spinal lesions were evaluated according to Tokuhashi score, Harrington score, Tomita score, vertebral stability assessment, and molecular targeted therapy. Aminokinase inhibitors, conservative treatment with local radiotherapy and bisphosphonate treatment. Results: During the follow-up period, the 1-year overall survival rate of the local treatment group was 100.0%, the 2-year overall survival rate was 89.4%, and the 5-year overall survival rate was 73.7%. The 1-year overall survival rate of the conservative treatment group was 87.5%, and the 2-year overall survival rate was 62.5%. The 5-year overall survival rate was 16.7%. The 2-year and 5-year survival rates of the local treatment group were statistically different (P=0.044, P=0.000) compared with the conservative treatment group. For patients with limb bone metastasis, the 5-year survival rate was significantly higher in patients receiving topical treatment than in the conservative treatment group (P=0.011). For spinal metastasis, spinal pain in the local treatment group was alleviated to varying degrees. No spinal instability and spasticity were observed after follow-up. In the spine patients who received conservative treatment, 3 patients developed paraplegia, which was statistically different from local treatment (P=0.046). Another 9 patients with multiple bone metastases did not undergo local surgery, and all died after multiple organ failure. Conclusions At the same time of molecular targeted therapy, according to the evaluation results, selective treatment of bone metastases with secondary surgical indications, including complete resection of the extremities and spinal fixation, can significantly improve the survival and quality of life of those patients.

Objective To investigate the relevant prognostic factors of liposarcoma ( LPS ). Methods The data of 78 patients with LPS treated in our hospital from July 2009 to March 2017 were reviewed. The 78 patients included 41 males and 37 females, and the average age was (60.5 ±13.4) years ( ranged from 18 to 85 years). Among the 78 LPS patients, 27 were well?differentiated LPS, 13 were myxoid LPS, 35 were dedifferentiated LPS and 3 were pleomorphic LPS.The distribution of lesion location included 40 cases of extremities and 38 cases of retroperitoneal. 21 cases were treated with radical excision, 57 cases were treated with marginal resection. 7 patients were treated with postoperative radiotherapy and 9 patients with postoperative chemotherapy. Progression free survival (PFS) and overall survival (OS) of LPS patients were analyzed as clinical outcomes. Prognostic factors were analyzed by univariate and multivariate analyses. Results 43 patients had local recurrence ( 9 of extremities／ 34 of retroperitoneal ), 18 patients with metastasis (4 of extremities／ 14 of retroperitoneal). The 5?year PFS rate was 31.4% and 5?year OS rate was 44.3%. Univariate analysis showed that the histological subtype and the tumor location were related with PFS ( P＜0.05), while the histological subtype, the tumor location, the tumor size, the recurrence and metastasis were related with OS (P＜0.05). Multivariate cox regression analysis showed that the tumor location was the independent prognostic factor of PFS (P＜0.05), while the histological subtype and metastasis were the independent prognostic factors of OS (P＜0.05). The median PFS of patients with myxoid LPS treated with radiotherapy was 34.6 months, which was significantly longer than 28.3 months of myxoid LPS patients without radiotherapy ( P＜0.05). Conclusions The tumor location is an independent prognostic factor of PFS in LPS patients.Retroperitoneal LPS is more prone to relapse and metastasize. OS is affected by pathological subtype and metastasis. Radiotherapy can improve the PFS of patients with myxoid LPS.

Objective To investigate the relevant prognostic factors of liposarcoma ( LPS ). Methods The data of 78 patients with LPS treated in our hospital from July 2009 to March 2017 were reviewed. The 78 patients included 41 males and 37 females, and the average age was (60.5 ±13.4) years ( ranged from 18 to 85 years). Among the 78 LPS patients, 27 were well?differentiated LPS, 13 were myxoid LPS, 35 were dedifferentiated LPS and 3 were pleomorphic LPS.The distribution of lesion location included 40 cases of extremities and 38 cases of retroperitoneal. 21 cases were treated with radical excision, 57 cases were treated with marginal resection. 7 patients were treated with postoperative radiotherapy and 9 patients with postoperative chemotherapy. Progression free survival (PFS) and overall survival (OS) of LPS patients were analyzed as clinical outcomes. Prognostic factors were analyzed by univariate and multivariate analyses. Results 43 patients had local recurrence ( 9 of extremities／ 34 of retroperitoneal ), 18 patients with metastasis (4 of extremities／ 14 of retroperitoneal). The 5?year PFS rate was 31.4% and 5?year OS rate was 44.3%. Univariate analysis showed that the histological subtype and the tumor location were related with PFS ( P＜0.05), while the histological subtype, the tumor location, the tumor size, the recurrence and metastasis were related with OS (P＜0.05). Multivariate cox regression analysis showed that the tumor location was the independent prognostic factor of PFS (P＜0.05), while the histological subtype and metastasis were the independent prognostic factors of OS (P＜0.05). The median PFS of patients with myxoid LPS treated with radiotherapy was 34.6 months, which was significantly longer than 28.3 months of myxoid LPS patients without radiotherapy ( P＜0.05). Conclusions The tumor location is an independent prognostic factor of PFS in LPS patients.Retroperitoneal LPS is more prone to relapse and metastasize. OS is affected by pathological subtype and metastasis. Radiotherapy can improve the PFS of patients with myxoid LPS.

Objective To summarize the current status and trend of hypoglycemic agents of diabetic inpatients in different departments of Chinese PLA General Hospital.Methods The clinical data of diabetic patients admitted to Chinese PLA General Hospital from January 2000 to May 2014 were collected(those hospitalized in the department of endocrinology were excluded).A total of 10 041 patients were selected by stratified random sampling.The type of hypoglycemic agents in different departments and the variation on anti-hyperglycemic drugs with time were retrospectively analyzed.Results Of all the patients in non-endocrinological wards, 50.2% were treated with insulin, 36.9% with metformin, 21.3% with α-glycosidase inhibitor, and 18.9% with sulfonylureas.Metformin, α-glucosidase inhibitors, pre-mixed 30R, and insulin glargine were more commonly used than other anti-hyperglycemic agents, accounting for 36.9%, 21.0%, 14.0%, 8.7%, respectively.Metformin, sulfonylureas, α-glucosidase inhibitor, and different types of insulin were more widely applied in internal medicine while insulin therapy was more frequently used in surgical department.During the past 15 years, the proportions of insulin, glinides, α-glucosidase inhibitor, and thiazolidinediones application were gradually increased, while the proportions of sulfonylureas and metformin treatment were on the decline trend.Conclusion Most of the inpatients were treated with oral antidiabetic drugs.Metformin, α-glucosidase inhibitor, pre-mixed 30R, and insulin glargine were the most frequently prescribed agents for the inpatients.