Objective To evaluate the molecular mechanism of 11 beta-hydroxysteroid dehydrogenase type 1 (11 β-HSD1)in tumor necrosis factor-α (TNF-α) induced insulin resistance.Methods The optimal concentration and incubation time of TNF-α for treating HepG2 cells were selected.Real-time polymerase chain reaction(PCR)and Western blot analysis were used to explore the effect of TNFα on the mRNA and protein expression levels of 11β-HSD1,glucocorticoid receptor (GR),phosphoenolpyruvate carboxylase(PEPCK)and glucose 6-phosphatase(G6Pase).Glucose(GO) Assay Kit was used to determine the level of gluconeogenesis.Liver/Muscle glycogen assay kit,PAS/Glycogen Stain kit were used to detect glycogen synthesis.The expression of AKT/GSK pathway was analyzed by Western blot analysis.In addition,HepG2 cells were pre-treated with BVT2733,a specific inhibitor of 11β-HSD1,before exposure to TNFα The expression of AKT/GSK pathway,the level of gluconeogenesis and glycogen synthesis were analyzed.Results The expression of 11β-HSD1 was increased along with the increasing concentration of TNF-α,showing a dose-dependent effect.When HepG2 cells treated with the optimal dose of TNF-α 10 μg/L for 24 hours,the levels of GR,gluconeogenesis and gluconeogenesis-related genes PEPCK and G6Pase were increased,while conversely,the levels of phosphorylation of AKT and GSK,and glycogen synthesis were decreased.However,all the above effects induced by TNF-α in HepG2 cells were greatly reversed by BVT2733 pre treatment.Conclusions 11 β-HSD1 participates in TNF-α-induced insulin resistance in HepG2 cells,and BVT2733 could significantly improve insulin sensitivity.

[Summary] Graves'ophthalmopathy ( GO) is the most common extrathyroidal manifestation of Graves disease ( GD) . It is an organ-specific autoimmune disorder. The estimated incidence of GO in the general population is 16 women and 3 men per 100,000 population every year. Approximately 3%-5% of patients with GO are exposed to the potential of losing their sight and requiring optimized medical intervention. For the clinicians it is helpful to assess the degree of activity and severity of GO;both are important in deciding whether a patient requires intervention and which type of intervention is indicated. These interventions include management of hyperthyroidism, measures to relieve local symptoms, immunosuppressive therapies for active moderate and severe GO, and finally rehabilitative surgery for inactive patients.

Objective To investigate the expression of Vacuolar-H +-ATPase (V-ATPase) and P-glyeoprotein (P-gp) protein in colon carcinoma tissues,the correlation between the expression of V-ATPase and P-gp and their clinicopathological significance.Methods In samples from 80 cases of colon cancer,20 cases of colon adenoma and 10 cases of normal colonic mucosa tissues,the expression of V-ATPase and P-gp protein were detected by immunohistochemical method,their relationship was analyzed,the clinicopathological features and prognosis were evaluated.Results In colon cancer,V-ATPase and P-gp protein expression was 72％ and 80％,higher than that in colon adenomas (40％,35％),and in normal colon mucosa (20％,20％),the difference was statistically significant (P ＜ 0.05).There was a positive correlation between the expression of V-ATPase and that of P-gp (r =0.567,P ＜0.01).V-ATPase and P-gp protein expression in colon cancer was associated with TNM stage,lymph node metastasis and tumor differentiation (P ＜ 0.05).Patients with high V-ATPase expression had lower 5-year survival rate than those with low V-ATPase expression (P =0.023),and 5-year recurrence rate was higher than those with low expression (P =0.024).Conclusions The expression of V-ATPase is up-regulated in colon cancer,there is a positive correlation with colon cancer progress and metastasis,and high V-ATPase protein expression predicts poor prognosis.

Objective To investigate the effect of omeprazole combined with FOLFOX scheme as an adjuvant therapy for stage Ⅱ or Ⅲ colon cancer patients after a radical resection.Methods 98 stage Ⅱ or Ⅲ colon cancer patients in our hospital from January 2008 to December 2009 were randomly divided into study group (48 cases) receiving regimen of omeprazole combined with FOLFOX and control group (50 cases) treated with FOLFOX chemotherapy after radical colectomy.Surgical specimens were examined for expression of V-ATPase protein.Chemotherapy period was 6 months,8-12 courses.We observed results of follow-up curative effect,comparing the side effects and postoperative 2 year,3 year and 5 year disease-free survival rate (DFS) difference using statistical analysis.Results Study was completed in all 93 cases,5 cases were lost to follow-up.The baseline data distribution in the two groups were balanced basically.In study group the gastrointestinal side effects of chemotherapy was lower than the control group (x2 =4.924 6,P =0.026).In the two groups,the 2-year,3-year and 5-year DFS were 73％ vs 60％ (x2 =1.743 7,P =0.187),62％ vs50％ (x2 =1.4075,P=0.235),49％ vs40％ (x2 =0.8159,P=0.366) (P＞0.05).V-ATPase protein expression was 71％ (70/98) in all samples.The 2-year and 3-year DFS of patients for V-ATPase protein positive expression in the two groups were 75％ vs 51％ (x2 =3.970 8,P =0.046),66％ vs 40％ (x2 =4.399 5,P =0.036).Compared with the control group,the 2-year,3-year DFS increased in the study group (P ＜ 0.05).In stage Ⅲ colon cancer patients,the 2-year DFS was 73％ vs 47％ (x2 =4.504 5,P =0.034).Conclusions PPI combined with FOLFOX in V-ATPase protein positive expression or Ⅲ stage colon cancer patients after radical colectemy improves long-term survival,as well as reduces the gastrointestinal side effects of chemotherapy.

Objective To analyze clinical charaCteristics and diagnostic experience on thyrotropinoma (TSHoma).Methods Clinical characteristics,laboratory findings,diagnostic experience,and surgical outcome were summarized from 16 cases of TSHoma in our hospital from January 2006 to September 2011.Results ( 1 )Among 16 cases ( 9 male,7 female ) aged ( 51.63 ± 13.23 ) years,14 ( 87.5 ％ ) cases presented with hyperthyroidism and 2 were diagnosed by physical examination. None of them had exophthalmos, acropachy, or pre-tibial myxedema.( 2 ) Serum FT4 and FT3 levels were all above normal range with serum TSH ( 4.37 ± 2.77 ) μIU/ml.There were 25％ (4/16) cases with positive serum thyroglobulin antibody and/or thyroid peroxidase antibody,none with positive TSH receptor antibody.TRH stimulating test was performed in 9 cases,3 were with positive response ( peak TSH level increased by 5.45-9.20 μIU/ml compared with baseline),and 6 without response (peak TSH level increased by -0.01-3.15 μIU/ml compared with baseline).TSH was suppressed to 27.15％ (5.19％-99.15 ％ ) of the baseline in 11 cases in which somatostatin suppression test was carried out.Prolactin and insulin-like growth factor-Ⅰ levels were increased in 2 cases.MRI performed in 15 patients showed 10 cases of microadenomas and 5 cases of pituitary adenoma.A mass in nasal cavity was found in one case,where no mass was found in the pituitary.( 3 )Surgery was made in 11 cases ( 9 patients underwent transsphenoidal operation,one craniotomy,and one underwent operation via endoscopic nasal septum ). All patients (11/11) were proved to yield pituitary adenoma pathologically.Conclusion Thyrotropinoma should be considered in hyperthyroidism with unsuppressed TSH level,and dynamic tests facilitated early diagnosis.Ectopic thyrotropinoma shoull be considered when normal pituitary morphology was shown by MRI.

Medullary thyroid cancer (MTC) is characterized hy the secretion of calcitonin that is derived from parafollicular cells.20％-25％ of MTC are hereditary.Compared with other types of thyroid cancer,MTC is prone to recurrence,metastasis,and younger onset age.RET gene germline mutation accounts for the hereditary MTC,and somatic mutation is responsible for part of sporadic cases.A good correlation between phenotype and genotype is reported.We present in this article a case of medullary thyroid cancer patient with genetic diagnosis and treatment as well as postoperative follow-up together with RET gene screening results in her family members in order to call attention to the diagnosis and treatment of MTC.

AIM: To study the effect of wild-type p53 gene on the differentiation, apoptosis and expression of scavenger receptor CD36 in U937 cells. METHODS: Recombinant adenovirus vector with wild-type p53 gene was constructed and used to transfect U937 cells. With the expression of wild-type p53 gene following adenoviral infection, transfected U937 cells were largely promoted to differentiate into macrophages. RESUITS: Trypanblue-staining test demonstrated that the percentage of positive cells increased from (14.2±5.5)% to (64.6±9.2)% and nitroblue tetrazolium (NBT) reduction test reached similar results (6.3±1.8)% vs (49.7±12.6)%. Furthermore, CD36 mRNA was up-regulated as confirmed by RT-PCR. The increased expression level of CD 36 was also detected by flow cytometry analysis. CONCLUSION: These results suggest that wild-type p53 gene can affect U937 cells differentiation and apoptosis, up-regulate expression of scavenger receptor CD36. It may have a potential significance on atherogenesis.

[Summary]_ This is a pedigree of multiple endocrine neoplasia type 1(MEN1). The proband pursuit medical assistance because of hypertension and weakness. Adrenal cortical carcinoma with possible Cushing's syndrome was diagnosed after a series of tests. During this process, the proband was found to have hypercalcemia, and he was diagnosed as primary hyperparathyroidism. Adrenal carcinoma plus primary hyperparathyroidism suggested MEN1, which was confirmed by MEN1 gene 400_401insC mutation. Pedigree investigation found six additional patients, including one with high parathyroid hormone level and two without clinical evidence of any MEN1 diseases. The proband died of metastatic malignancy 7 months after diagnosis while the other 3 patients with clinically confirmed MEN1 tumor responded well to surgery, including one with adrenal cortical carcinoma.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.