Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated disease and one of immunoglobulin G4-related diseases (IgG4-RD). Our multidisciplinary research group investigated the clinicopathological characteristics and diagnosis of IgG4-RS during the past 10 years. Clinically, it showed multiple bilateral enlargement of major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands. The comorbid diseases of head and neck region including rhinosinusitis, allergic rhinitis, and lymphadenopathy were commonly seen, which could occur more early than enlargement of major salivary glands. Internal organ involvements, such as autoimmune pancreatitis, sclerosing cholangitis, and interstitial pneumonia could also be seen. Thirty-five (38.5%) patients had the symptom of xerostomia. Saliva flow at rest was lower than normal. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in almost all the cases and the majority of the patients had increased IgE levels. CT, ultrasonography, and sialography showed their imaging characteristics. Histologically it showed marked lymphoplasmacytic inflammation, large irregular lymphoid follicles with expanded germinal centers, prominent cellular interlobular fibrosis, eosinophil infiltration, and obliterative phlebitis. Their immunohistological examination showed marked IgG-positive and IgG4-positive plasma cell infiltration and high IgG4/IgG ratio. The disease could be divided into three stages according to severity of glandular fibrosis. The serum IgG4 level was higher and the saliva secretion lower as glandular fibrosis increased. IgG4-RS should be differentiated from other diseases with enlargement of major salivary gland and lacrimal gland, such as primary Sjögren syndrome, chronic obstructive submandibular sialadenitis, and eosinophilic hyperplastic lymphogranuloma.
Autoimmune Diseases ; Humans ; Immunoglobulin G ; Sialadenitis ; Sjogren's Syndrome ; Submandibular Gland

Objective To improve the early diagnosis of congenital heart disease (CHD), investigate the awareness, screening knowledge and screening ability of CHD among health care providers in the rural areas of Yunnan province and discover an effective way to improve the related knowledge and skills of CHD screening. Methods From 2015 September to 2017 April, we set up charity mobile schools and chose eight areas as the investigating and training sites. We designed two questionnaires, and adopted the theoretical training as the main method combined with the training of clinical skills. We investigated and trained a total of 1022 medical staff. The training content include the awareness of CHD,the knowledge and skills of CHD screening. We also evaluated the outcomes of the training. Results A total of 2044 questionnaires were collected. After training, the number of objects which would screen CHD in future increased, and the cognition of the incidence and common clinical manifestations of CHD, Eisenmanger's syndrome,cardiac auscultation, pulse oximetry and the related knowledge of CHD were also improved; 563 took the test on practical skills of CHD detection. The correct rate of auscultation, period of murmurs and characteristics of murmurs was 98.22%(553),30.55%(172) and 28.60%(161). The correct rate of murmurs in ventricular septal defect,atrial septal defect and patent ductus arteriosus was 45.47%(256), 39.79 (224) and 50.80%(286) respectively. Online training was advised by 244 trainees. Increasing investment in congenital heart disease screening was suggested by 652 trainees. Conclusions The awareness of CHD screening in grassroots medical workers of Yunnan province is insufficient. It is an effective way to establish charity mobile school and to train the grassroots medical staff with the theory and practical knowledge to improve the awareness,screening knowledge and screening skills of CHD. The next step suggests that we can improve the early diagnosis of congenital heart disease (CHD).

AIM:To investigate the synergistic effect of imperatorin on enhancing the anti -tumor effect of TNF-related apoptosis-inducing ligand(TRAIL)on breast cancer and the mechanisms.METHODS:T-47D and MCF-7 breast cancer cells were divided into control group ,imperatorin group,TRAIL group,imperatorin+TRAIL group and imperatorin+TRAIL+death receptor 5(DR5)siRNA group.The viability of T-47D and MCF-7 cells was measured by MTT assay. The apoptosis and mitochondrial membrane potential in T-47D cells were analyzed by flow cytometry.Western blot and flow cytometry analysis were performed to evaluate the expression of DR 5 on T-47D cell surface and the activation of caspase-8 and caspase-3.RESULTS:Imperatorin significantly enhanced the inhibition of cell viability induced by TRAIL of T -47D and MCF-7 cells,and significantly increased the apoptosis of T-47D cells induced by TRAIL.Imperatorin treatment ob-viously induced upregulation of DR5 expression and production of reactive oxygen species in the T-47D cells.In addition,imperatorin enhanced the TRAIL-induced damage of mitochondrial membrane potential and activation of caspase -8 and caspase-3.CONCLUSION:Imperatorin enhances the anti-tumor effect of TRAIL on breast cancer via upregulating the ex-pression of DR5.

Objectives: To describe the differences between patients with angiography confirmed stent thrombosis in antiplatelet therapy and long term outcomes. Methods: We analyzed data from 1 204 patients with angiography – documented stent thrombosis between January 2008 to December 2016 in Beijing Anzhen Hospital. According to the timing of stent thrombosis post stent implantation, patients were divided into acute stent thrombosis (<24 h, n=106), subacute stent thrombosis(24 h~30 d, n=206), late stent thrombosis (>30 d~1y, n=268), and very late stent thrombosis (>1 y, n=624) groups. Death, recurrent stent thrombosis, recurrent myocardial infarction, target vessel revascularization, stroke and antiplatelet treatment during In-hospital or long-term clinical follow-up were compared among groups. Results: Prevalence of stent thrombosis was the highest in the left anterior descending artery (51.9%) in acute stent thrombosis group. Subjects with subacute stent thrombosis had a higher prevalence rate of LVEF<50% (28.2%), and subjects with very late stent thrombosis had a higher prevalence rate of diabetes (34.1%). All patients in acute stent thrombosis group received aspirin + clopidogrel, 96.5% patients in subacute stent thrombosis group and 94.5% patients in late stent thrombosis group were treated with double or triple antiplatelet therapy, while 95.2% patients in the very late stent thrombosis group were treated with double or mono antiplatelet therapy. During the follow up, mortality was 23.6%, 26.7%, 26.3% and 18.9% in acute stent thrombosis, subacute stent thrombosis, late stent thrombosis, and very late stent thrombosis groups, respectively. Conclusions: Most patients with angiography–documented stent thrombosis are treated with recommended antiplatelet therapy. Development of stent thrombosis is associated with poor outcomes.

Objective To investigate the correlation and significance of S100A12 with obstructive sleep apnea hypopnea syndrome (OSAHS).Methods Fifty-three patients with OSAHS were chosen as OSAHS group and 46 healthy volunteers were chosen as control group.The levels of S100A12 and hs-CRP in the two groups were compared,and its relationship with those of epworth (ESS),apnea hypopnea index (AHI),and minimum blood oxygen saturation (L-SpO2) were analysised.Results The scores of ESS,BMI,A HI,L-SpO2,hs-CRP and S100A12 in two groups were statistically significant (P＜0.05).The severity of hs-CRP in severe OSAHS group was significantly higher than that of mild OSAHS group (P＜0.05).There was no significant difference in hs-CRP between moderate OSAHS group and mild OSAHS group and severe group (P＞0.05).The level of S100A12 in severe OSAHS group was significantly higher than that of moderate OSAHS group and OSAHS mild group(P＜0.05).The level of S100A12 in moderate moderate group was significantly higher than that of mild group(P＜0.01).hs-CRP was negatively correlated with ESS and AHI (r=0.822,0.787,P＜0.01),was positively correlated with L-SpO2 (r=-0.740,P＜0.01),S100A12 was positively correlated with ESS and AHI (r =0.707,P ＜ 0.01),and negatively correlated with ESS and AHI (r =0.707,0.807,P＜0.01),and negatively correlated with with L-SpO2 (r=-0.670,P＜0.01).Conclusion S100A12 is associated with OSAHS.The higher the severity of OSAHS,the higher the S100A12 value,which can be used as a new predictor of cardiovascular disease risk in OSAHS patients.

Objective:To compare influence of percutaneous coronary intervention(PCI)and thrombolytic therapy on therapeutic effect and reperfusion in patients with acute myocardial infarction(AMI).Methods:A total of 118 AMI patients treated in our hospital from Jan 2013 to Dec 2016 were enrolled.They were divided into thrombolysis group (n=38)and PCI group(n=80).Therapeutic effect,cardiac function and reperfusion indexes were compared be-tween two groups.Results:Compared with thrombolysis group,there was significant rise in total effective rate (84.21% vs.97.50%),and significant reduction in total incidence rate of adverse events(18.42% vs.2.50%)in PCI group,P< 0.01 both.Compared with before treatment,there were significant reductions in left ventricular end-systolic dimension(LVESd)of two groups and left ventricular end-diastolic dimension(LVEDd)of PCI group, and significant rise in creatine kinase isoenzyme-MB(CK-MB)level of two groups after treatment,P=0.001 all. Compared with thrombolysis group after treatment,there were significant reductions in LVEDd[(32.45 ± 2.21)mm vs.(29.86 ± 3.96)mm]and LVESd[(49.85 ± 1.32)mm vs.(46.86 ± 2.34)mm],and significant rise in CK-MB level[(389.74 ± 2.74)ng/ml vs.(706.96 ± 3.78)ng/ml]in PCI group,P=0.001 all.Conclusion:Compared with thrombolytic therapy,PCI possesses more significant therapeutic effect on AMI.It can more significantly im-prove patient′s cardiac function,and rise CK-MB level,which has better clinical value.

Objective To investigate the clinical efficacy and safety of oxaliplatin injection and tegafur-gimeracil-oteracil potassium capsule in the treatment of late-stage triple-negative breast cancer (TNBC).Methods A total of 120 patients with TNBC were randomly divided into control group(n =60)and treatment group (n =60).The control group received gemcitabine (1000 mg· m-2,intravenous drip,on the first day and the eighth day) and cisplatin (20 mg · m-2,intravenous drip,5 d).The treatment group received oxaliplatin (135 mg · m-2,intravenous drip,on the first day) and tegafur-gimeracil-oteracil potassium (40～60 mg,oral ad1ninistration,14 d).Both groups were treated for six 21-day cycles.If the disease progressed after six cycles,the treatment above will be replaced by other treatments.The clinical efficacy,and half year survival rate and the incidence of adverse drug reactions were compared between the two groups.Results After treatment,the overall response rates of the treatment group and the control group were 73.33％ (44 cases/60 cases) and 71.67％ (43 cases/60 cases),respectively,and no significant difference was found between the two groups (P ＞ 0.05).Six months after treatment,the survival rates of the treatment group and the control group were 85.00％ (51 cases/60 cases) and 81.67％ (49 cases/60 cases),with no significant difference (P ＞ 0.05);the adverse drug reactions in the treatment group and the control group were diarrhea,nausea and vomiting,and the incidences of adverse drug reactions were 18.33％ (11 cases/60 cases) and 21.67％ (13 cases/60 cases),respectively,and the difference was not significant (P ＞ 0.05).Conclusion Both combination treatment (oxaliplatin combined with tegafur-gimeracil-oteracil potassium,gemcitabine combined with cisplatin) exerted high clinical efficacy in the treatment of late-stage TNBC,and the six-month survival rates were high.

Objective To investigate the short-term efficacy,survival rate of docetaxel + cisplatin + 5-fluorouracil (DCF) and docetaxel + cisplatin (DP) combined with chemo-radiotherapy regimens in patients with stage Ⅲ-ⅣB nasopharyngeal carcinoma.Methods A total of 230 patients with Ⅲ-Ⅳ B nasopharyngeal carcinoma in our hospital were randomly divided into treatment group and control group,115 cases in each group.Control group were received concurrent radiotherapy and chemotherapy for 3 courses.On 1-3 d,patients were treated with intravenous infusion docetaxel (DTX) 100 mg · m-2,on second day intravenous infusion cisplatin (DDP) 75 mg · m-2,and 21 d a course.Treatment group were received 2 courses of radiotherapy and chemotherapy.On the first day,patients were given intravenous infusion docetaxel 75 mg · m-2,cisplatin 75 mg · m-2,1-5 d intravenous infusion 5-fluorouracil (5-FU) 750 mg · m-2,and 21 d a course.During the treatment,the blood was examined every week,heart,lung and kidney function was reexamined every 2 weeks.The short-term efficacy,nasopharyngeal lesions and neck metastasis,lymph node regression,adverse drug reactions and survival rate were observed in two groups.Results After treatment,the tumor target volume in treatment group was (36.44 ± 4.29) cm3,the reduction rate was 25.63％,had no significant difference with those in control group,which were (36.36 ±5.10)cm3,25.92％ (P ＞0.05).The response rates of control group and treatment group were 99.13％ and 100.00％ (P ＞ 0.05).Patients in grade Ⅲ and Ⅳ stratified analysis showed that the overall survival(OS),metastasis free survival (MFS),tumor recurrent free survival (TRFS) in grade Ⅲ had significant difference in two groups (P ＜0.05).The OS,MFS,disease free survival (DFS) of grade Ⅳ in two groups all had significant difference (P ＜ 0.05).The incidence of leucopenia,hemoglobin decreased,thrombocytopenia,nausea,vomiting and mucositis in two groups had significant difference (P ＜ 0.05).Conclusion Compared with DP and concurrent radiotherapy,DCF chemotherapy and concurrent radiotherapy can prolong the overall survival rate of patients with locally advanced nasopharyngeal carcinoma,but increase the incidence of adverse drug reactions.There is no significant difference between the two groups in short-term clinical effect.

[Objective] To investigate the environmental pollution status and infectious diseases in kindergartens and nurseries in 2012 in Baoshan District . [ Methods] The questionaire was used in com-bination with data from monitoring of the disinfection effect of environment , monitoring analysis of routine infectious disease and others . [ Results] The overall pass rate was 97.91% for environmental disinfec-tion in kindergartens and nurseries , and it was higher in public kindergartens and nurseries than in private ones.The conventional infectious disease in kindergartens and nurseries was mainly hane-foot-and-mouth disease (HFMD), whose incidence was higher in private kindergartens and nurseries than in public ones . And in terms of regional distribution , the incidence of HFMD was higher in streets and towns with more in-floating population than those with less .And the pass rate for the disinfection effect on the kindergartens nurseries and the incidence rate of HFMD were negatively correlated . [ Conclusion] Kindergartens and nurseries in our district should strengthen the complete configuration of hardware and software , establish standardized system of disinfection and isolation , and develop daily disinfection system , so as to reduce in-fectious disease .