Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective To explore the efficacy and safety of fluoroscopy-guided balloon dilation for esophageal strictures in patients with epidermolysis bullosa(EB).Methods The clinical data and follow-up results of EB patients,who received fluoroscopy-guided balloon dilation due to esophageal stricture at Shanghai Xinhua Hospital from May 2020 to May 2023,were retrospectively collected.The therapeutic efficacy and the prognosis of this treatment method were analyzed.Results A total of 17 EB patients received fluoroscopy-guided balloon dilation treatment due to dysphagia caused by esophageal stricture.Most esophageal strictures were single-site stenosis(13/17,76.5％)and it commonly occurred in the esophageal cervical segment(12/17,70.6％)and the upper thoracic segment(8/17,47.1％)of esophagus.Two patients developed esophageal bleeding after dilatation and no special treatment is required.No other post-treatment complications were observed.In most of the patients(15/17,88.2％)a long-term improvement of the dysphagia symptoms could be obtained after receiving a single balloon dilation treatment.By the last follow-up visit,most of the patients(15/17,88.2％)gained more weight when compared with their pre-treatment body weight,with an average increased weight of 2.97 kg.Conclusion Clinically,EB is a rare etiology that can cause an esophageal stricture.This esophageal stenosis is characterized by a single stenosis mostly located in the upper segment of the esophagus.Fluoroscopy-guided balloon dilation is an effective and safe treatment for this type of esophageal strictures.

Objective:To summarize the clinical characteristics, reveal evolutionary patterns, and enhance the understanding of idiopathic isolated adrenocorticotripin(ACTH)deficiency(IIAD)by conducting a clinical analysis and follow-up.Methods:The clinical data of 12 patients with IIAD in our center were analyzed retrospectively, and the patients were further followed up to summarize the clinical characteristics of these patients.Results:Among 12 patients with IIAD, the ratio of male to female was 3∶1. The onset showed a bimodal trend, with 2 cases occurring below the age of 18(at 1 year and 11 years respectively), and 10 cases occurring in adults, with an average onset age of 59.4 years old. In adults, the main symptoms were chronic fatigue, anorexia, and weight loss, while pediatric patients exhibited hypoglycemia and seizures. Hyponatremia(50%)was a common biochemical abnormality. ACTH, cortisol, and 24 h urinary free cortisol were significantly lower in all patients, and the functions of other pituitary gland axes were normal. All patients were normal except 2 patients with pituitary MRI showing vacuolar sella turcica. The most common accompanying disease was Hashimoto thyroiditis. After glucocorticoid replacement therapy, all patients showed symptom improvement. The replacement doses include prednisone acetate at 2.5-7.5 mg/d or hydrocortisone at 12-20 mg/d. All the 8 patients were still alive with ongoing ACTH deficiency, without any decline in other pituitary axis functions or occurrence of other diseases.Conclusion:IIAD exhibits a bimodal onset pattern with a higher prevalence in males. Symptoms persist in a chronic and stable manner without remission. Prognosis is favorable with physiological dose of glucocorticoid replacement therapy.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in adults with type 2 diabetes (T2D). The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) guidelines on diabetes, pre-diabetes, and CV diseases. METHODS: A total of 25,411 patients with T2D, who participated in the study of China Cardiometabolic Registries 3B study, were included in our analysis. We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines. RESULTS: Based on the 2019 ESC/EASD guidelines, 16,663 (65.6%), 1895 (7.5%), and 152 (0.6%) of patients were included in "very high risk," "high risk," and "moderate risk" categories, respectively. The proportions of patients in each category varied based on age, sex, body mass index, and duration. While 58.7% (9786/16,663) of elderly patients were classified to "very high risk" group, 89.6% (3732/4165) of patients with obesity were divided into "very high risk" group. Almost all patients with a duration of diabetes >10 years had "very high risk" or "high risk." However, 6701 (26.4%) of Chinese T2D patients, who had shorter duration, and one or two risk factors, could not be included in any category (the "unclear risk" category). CONCLUSIONS In China, most patients with T2D have "very high" or "high" CV risk based on 2019 ESC/EASD guidelines. However, the risk of patients in "unclear risk" group needs to be further classified.
Adult ; Aged ; Cardiovascular Diseases/epidemiology* ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Heart Disease Risk Factors ; Humans ; Risk Factors

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.

Shanghai Jiao Tong University established the first biomedical science in China in 2016. Learning the successful experience from international universities can promote the development of this major. According to the comparison of cultivation program and curriculum system in different top universities at home and abroad, it was showed that Oxford University focused on the pluralism development of students, University of Technology Sydney paid attention to the combination of basis and clinical practice, and the University of Hong Kong stressed the integration of clinical practice, science and research, and transformation. Through the exploration of the details of educational system this university, we found that we mainly focused on five innovation ideas: building the basic knowledge, strengthening comprehensive basic knowledge teaching, stimulating students' interests towards biomedical science, developing their ability and promoting innovative education and training. Based on analysis of those cases, it is showed that the development of biomedical science in China should solve problems in curriculum integration and practical education of science and research, so as to achieve the goal to cultivate more talents in this major and boost the development and advances in the field of biomedical science.

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.

To study thyroid hormone receptor β(THRβ)gene mutation in a pituitary-resistance to thyroid hormone syndrome family. The peripheral blood samples of the patient, his sister, parents, and 4 maternal relatives were collected. Then serum was isolated for detecting thyroid hormone levels with chemiluminescence immunoassay, and DNA was extracted for PCR, and 10 exons of THRβ gene were sequenced. The patient and his mother had the hyperthyroid symptom for many years and his mother with atrial fibrillation. The G→A heterozygous transition mutation was confirmed by exon sequencing at nucleotide 949 within exon 9 of THRβ gene in the patient and his mother, which was a missense mutation causing a substitution of Alanine to Threonine(A317T). No mutation was found in THRβ gene in other family members. This is the first Chinese family reported with pituitary thyroid hormone resistance syndrome caused by a A317T mutation in the thyroid hormone receptor β gene.

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.