Type 1 diabetes mellitus(T1DM), which is an autoimmune disease, mostly affect people with hereditary susceptibility under the joint participation of environmental factors.It is known to coexist with other autoimmune disorders such as celiac disease(CD). The prevalence of CD is higher in patients with type 1 diabetes compared with the general population.Most patients affected with both T1DM and CD are atypical for CD at diagnosis, and may be misdiagnosed and subsequently suffered from the delayed treatment.These patients are more likely to develop symptomatic hypoglycemia, or poor blood glucose control, leading to an increased risk of chronic complications and seriously affecting the quality of their life.Thus, screening for CD is recommended in patients with T1DM.Anti-tissue transglutaminase antibody is the preferred biomarker for CD screening in children and adolescents over 2 years of age, with a sensitivity of 95% to 100% and a specificity of 94% to 100%.And a low-carbohydrate diet is often combined with a gluten-free diet.

Objective:To study the effect of recombined TNF ? combined with induction of apoptosis and its relation with expression of bcl 2 in SW480 human colon cancer cells.Methods:The inhibitive effect of 5 Fu and TNF ? was measured by MTT.Apoptosis of colon cancer cells was studied by TUNEL.The expression of bcl 2 gene was determined by immunohistochemical analysis.Results:After SW480 colon cancer cells were treated with combination in various concentration of 5 Fu and 3 000 U/mL of TNF ? for 48 h,MTT assay revealed a significant decrease of relative viability in compasrison to the control.When SW480 colon cancer cells were treated with 3 000 U/mL of TNF ? and 125 ug/mL of 5 Fu in combination for 48 h,TUNEL method showed the number of nick end positive cells was significantly increased in comparison to the control.The expression level of bcl 2 gene lowered significantly than that of the control group.Conclusion:These results confirmed that combined TNF ? and 5 Fu could synergistically induce apoptosis in SW480 cells and decrease the expression level of bcl 2 gene.

Objective To assess the risk of secondary transmission induced by imported malaria in Jiangxi Province，so as to provide the evidence for adjustment of malaria surveillance strategies in the key groups and areas. Methods The Delphi method was used to establish the secondary transmission risk indicator system and the weight of each index was obtained. The data of malaria prevalence，vector distribution and intervention capacity were collected in 100 counties of Jiangxi Province from 2012 to 2015. The transmission potential index（TPI），intervention capacity index（ICI），and malaria risk index（MRI）were calculated for each county. The risk map was drawn with GIS software. Results The top ten counties with highly potential risk indicators were Linchuan District（2.131），Xinzhou District（1.609），Jiujiang County（1.404），Zhanggong District（1.365）， Fengcheng City（1.225），Qingshanhu District（1.184），Yudu County（1.171），Dingnan County（1.018），Xunyang District（1.015）and Zhushan District（1.006）. The high risk areas were mainly distributed in the regions of the capitals of their prefectures and in counties with more floating population. Conclusions There are the risk of the secondary transmission induced by imported malaria in Jiangxi Province. The high risk of the secondary transmission is shown in the areas with more floating population and weaker intervention capacity.

Objective To study the therapeutic window of rapamycin(RPM) concentration in primary recipients of renal transplantation. Methods An open label, multi center study was performed. One hundred primary renal allograft recipients with cadaveric donors were enrolled from 4 transplantation centers in China. The immunosuppressive regimen was triple therapy,i.e.RPM combined with CsA and steroid. A loading dose of RPM 6 mg/d was administered within 48 hours after transplantation, then a maintaining dose of 2 mg/d was administered. The whole blood concentration of RPM was measured by HPLC method. Results The whole blood concentration of RPM in this group was (6.65?2.75)ng/ml, the 10th and 90th percentile for RPM concentration was 3 2 ng/ml and 10 26 ng/ml,respectively.9 5%(8/84)patients suffered from acute rejection during the 6 month period after transplantation in this study, and the concentration of RPM in these was lower than that in non rejection patients(P=0.001). Hyperlipidemia and liver dysfunction were the most frequently adverse events, and RPM concentration was significantly associated with the concentration of triglyceride. Conclusions 4～8 ng/ml is a suitable level for RPM concentration. Regular drug monitoring and reasonable dose modulation may increase the validity and security of RPM.

Objective To master the disease trend of Keshan disease in Liaoning Province, and provide a scientific basis for control and elimination of Keshan disease. Methods Retrospective method was used to analysis the Keshan disease monitoring in Liaoning Province.From 1995 to 2007,a sentinel surveillance method was used in Qingyuan County,and seriously ill villages were selected as monitoring sites. From 2008 to 2014, a sample random sampling method was adopted to randomly select 1 - 4 diseased villages as monitoring sites in Qingyuan, Xinbin, Huanren and Xifeng each year. The residents in surveillance sites were surveyed through questionnaire, clinically examined and did electrocardiogram (ECG), suspected cases were taken anterior chest X-rays in the distance of 2 meters, and diagnosis of Keshan disease was based on the "Standard of Diagnosis of Keshan Disease" (GB 17021-1997)and the"Keshan Disease Diagnosis" (WS/T 210-2011). Results From 1995-2014,no new cases of acute and subacute Keshan disease were detected in Keshan disease monitoring sites in Liaoning Province,Keshan disease detection rate was the highest in 2007(6.6%,55/838),the lowest was in 2012(0.4%,3/836),cases of Keshan disease had been concentrated among non-key groups,the highest abnormal rate of ECG was found in 2011 (24.5%,424/1 728), for 176 cases of suspected Keshan disease, the anterior position of 2 m chest X-ray was taken and 50.0% (88/176) of the changes were increased. Conclusion After 20 years of monitoring and prevention, the condition of Keshan disease in Liaoning Province has been in a relatively stable state. But we still should strengthen the monitoring of Keshan disease,emphasize the importance of case search,continue to carry out the monitoring.

Objective: To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells. Methods: Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-β/Smad pathway associated proteins TGF-β1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed. Results: Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05). Conclusion miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-β/Smad signaling pathway.

Objective:To investigate the clinical efficacy and safety of demethylating drugs decitabine and azacitidine in treatment of myelodysplastic syndromes (MDS).Methods:The clinical data of 15 patients initially diagnosed with MDS in Fujian Provincial Hospital from May 2010 to May 2020 were retrospectively analyzed; 10 patients were treated with decitabine (10-30 mg·m -2·d -1, 3-5 d consecutively) and 5 patients were treated with azacitidine (75 mg·m -2·d -1 for 7 d consecutively). Gene mutation, risk stratification, efficacy and adverse reactions were observed. Results:Among 15 patients, 9 cases were males and 6 cases were females, with a median age of 64 years (51-84 years). The median follow-up time was 18 months (4-62 months). There were 3 cases in high-risk group, 10 cases in medium-risk group and 2 cases in low-risk group. SF3B1, TET2 and STAG2 mutations were more common in patients with low to moderate risk; DNMT3A, EZH2, U2AF1, RUNX1 and TP53 mutations were more common in patients with high-risk. All patients were evaluated for efficacy after 2-3 courses of treatment, and the total effective rate was 66.7% (10/15). Among them, 1 case (6.7%) achieved complete remission, 1 case (6.7%) achieved bone marrow complete remission (mCR), 2 cases (13.3%) achieved partial remission, and 6 cases (40%) achieved hematological improvement. During the treatment, 9 cases had grade 3-4 hematological toxicity and 6 cases had grade 3-4 infection. There was no grade 3-4 bleeding, nausea, vomiting and liver function damage. During the follow-up to May 2020, 9 patients survived and 6 patients died.Conclusions:Demethylating drugs decitabine and azacitidine have high rates of complete remission and partial remission and a low rate of adverse drug reactions in MDS patients.

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).