Objective To discuss the therapeutic effect of recombinant human CTLA-4Ig fusion protein (rhCTLA-4Ig) on rheumatoid arthritis (RA) patients and the change of T helper cells 17 (Th1 7 ) and regulatory T (Treg) cells.Methods Forty-eight active RA patients were randomly divided into the treatment group and the control group.Treatment group received 12 weeks of infusions of rhCTLA-4Ig ( 10 mg/kg),while the control group received 12 weeks of infusions of placebo.The changes of expression levels of Th17cell were detected by flow cytometry.The changes of expression level of FoxP3 in monocytes of the peripheral blood were examined by RT-PCR.T test and x2 test were used for statistical analysis.Results ① Eighteen of 24 cases in treatment group showed good ACR20 changes after 12 weeks,the effective rate (75％) was significantly higher than that of the control group ( 1/24,4％ ).After treatment,DAS28 score of the treatment group (3.0±0.7) was significantly lower than that of the control group(6.9±0.7) (t=-12.39,P＜0.01 ).② Compared with the Th17 monocytes of the peripheral blood from active RA patients of treatment group after therapy (0.22±0.20)％,the Th17 monocytes of peripheral blood from active RA patients of the control group (1.63±0.47)％ were higher (t=5.61,P＜0.05 ).③ Compared with the FoxP3 mRNA of the control group (0.24±0.05),that of the treatment group (0.88±0.18) was significantly higher after therapy (t=7.56,P＜0.01 ).Conclusion The clinical parameters of RA patients have improved significantly after the treatment,and the Th17 and Treg cells balance is also restored after rhCTLA-4Ig therapy.

Objective To summarize the manifestation of solid pseudopapillary tumor of the pancreas (SPTP) on ultrasound and contrast-enhanced ultrasound (CEUS) and to investigate the diagnostic value of CEUS. Methods The ultrasound and CEUS images of six patients with SPTP confirmed by pathology were reviewed. According to CEUS record,the enhanced and wash-out time,enhanced speed and degree of tumor were analyzed. Results On ultrasound, SPTP presented as solid, well-circumscribed masses, usually heterogeneous in echo texture, and some of them contained macro-calcification. On CEUS, the tumor enhanced simultaneously or slightly late compared with normal pancreatic tissues. The contrast agent washed out quickly in all tumors than in normal pancreatic tissues. The enhanced degrees were equal to or less than that of the normal pancreatic tissues. Some tumors showed capsule and septum enhancement. Conclusions The manifestation of SPTP on CEUS had some features and may be helpful for differentiation diagnosis combine with ultrasound.

OBJECTIVE: To investigate the effect of n-hexane on the level of sex hormones and expression of estrogen receptor(ER) in rats and the protective effect of Lyciumbarbarum polysaccharide(LBP) on n-hexane-induced reproductive toxicity. METHODS: Based on factorial design model of 4×2, specific pathogen free adult female SD rats were divided into control group and low-, medium-and high-n-hexane exposure groups, and each group was divided into non-LBP intervention and LBP intervention sub-group. There were 8 subgroups with 6 rats in each group. On the first day, the rats in the 4 groups were given intraperitoneal injection of n-hexane at 0, 675, 1 350 and 2 700 mg/kg body weight, respectively. On day 2-4, the rats in the non-LBP intervention subgroup were given intragastric administration of 0.9% sodium chloride solution, and the rats in the LBP intervention subgroup were given intragastric administration of LBP at 50 mg/kg body weight once a day. On the fifth day, all animals were sacrificed, and the levels of follicle stimulating hormone(FSH), luteinizing hormone(LH), estradiol, progesterone were detected by enzyme linked immunosorbent assay. The mRNA expression of Erα, Erβ and G protein coupled estrogen receptor 1(Gper1) was detected by real time fluorescence polymerase chain reaction, and the expression of ERα, ERβ and GPER1 protein was detected by Western blotting. RESULTS: i) In the absence of LBP intervention(i.e. simple n-hexane exposure), there was no significant difference in the level of serum FSH, LH, estradiol and progesterone in the 4 groups(P>0.05). The relative expression of Erβ mRNA in ovary of low dose group decreased, while the relative expression of proteins of ERα and GPER1 increased(P<0.05) when compared with the control group. The relative expression of Erα mRNA and GPER1 protein in the ovary of medium-and high-dose groups increased(P<0.05), while the relative expression of Erβ, Gper1 mRNA and ERβ protein decreased(P<0.05). The relative expression of ERα protein in ovary of high-dose group increased(P<0.05). ii) At the same dose of n-hexane exposure, the relative expression of Erα mRNA in ovary of rats in low dose group increased(P<0.05), while the relative expression of ERβ and GPER1 protein decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). The relative expression of ERα and GPER1 protein in ovary of medium dose group increased(P<0.05), while the relative expression of Gper1 mRNA and GPER1 protein in ovary of high dose group decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). CONCLUSION: n-Hexane can up-regulate the expression of ERα and GPER1 in rat ovary, but has no significant effect on female endocrine system. LBP may play a protective role in female reproductive system by up-regulating the expression of ERα and GPER1.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

OBJECTIVE： To explore the effects of different primary processing methods on quality change of Polygonatum sibiricum， and to optimize primary processing method of P. sibiricum with different grades and shapes. METHODS： After processed with different drying methods， boiling method and steaming method， sulfuric acid-phenol method was used to determine the contents of indicator component P. sibiricum polysaccharide in samples. The contents of ethanol-soluble extract， water-soluble extract and total ash were investigated. The optimal primary processing methods were screened. RESULTS： After processed with different methods， the contents of polysaccharide （≥7％）， ethanol-soluble extract （≥45％） and total ash （≤4％） of samples at all levels conformed to the requirements of the 2015 edition of Chinese Pharmacopoeia （part Ⅰ）； from aspect of drying method， microwave drying method was better than oven drying method；for P. sibiricum with different morphologies （individual and lamellar）， the quality of lamellar samples of P. sibiricum was better than that of individual P. sibiricum. As primary processing method， steaming was better than boiling. The contents of P. sibiricum polysaccharide were in relatively high level， when the steaming and boiling time of gradeless and uniformly-priced goods of P. sibiricum were 20 and 15 minutes respectively. CONCLUSIONS： By discussing the different primary processing methods， high-efficient primary processing method for the individual and lamellar samples of P. sibiricum as well as gradeless and uniformly-priced goods of P. sibiricum are preliminarily obtained， which can provide a scientific basis for the effective utilization of P. sibiricum resources.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

OBJECTIVETo establish the risk model for predicting the progression within 1 year of patients with gastric neuroendocrine neoplasms(gNEN) and to evaluate its value of prediction.

METHODSClinical data of 127 gENE patients with histologically comfirmed sporadic gNEN from January 1999 to February 2015 in Nanfang Hospital of Southern Medical University(n=63) and The First Affiliated Hospital of Sun Yat-sen University(n=64) were collected retrospectively. Twenty-five patients without follow-up were excluded, so a total of 102 cases were enrolled in the analysis. Tumor size enlargement, lesion number increase, recurrence after resection of primary tumor and emergence of tumor metastasis were defined as tumor progression. Patients were divided into progression group (above definitions occurred within 1 year, n=56) and non-progression group (above definitions did not occur within 1 year, n=46). Logistic regression analysis was used to identify the influencing factors of progression within 1 year and the regression equation was acquired, then the probability of progression within 1 year of gNEN patients was obtained to predict the grading: grade I(: the probability of tumor progression within 1 year was < 25.0%; grade II(: this probability was from ≥25.0% to <50.0%; grade III(: this probability was from ≥50.0% to <75.0%; grade IIII(:this probability was ≥75.0%. Spearman correlation analysis was used to study the correlation between predictive grading and the occurrence of disease progression in patients with gNEN NET within 1 years. The ROC curve of different prediction methods was drawn, then the area under the curve(AUC), sensitivity and specificity were calculated and compared.

RESULTSMultivariate regression analysis showed that tumor size(OR=1.048, 95%CI:1.014-1.083, P=0.005), Ki-67 index(OR=2.045, 95%CI:1.261-3.316, P=0.004), and surgical resection of the primary lesion(OR=0.074, 95%CI:0.011-0.497, P=0.070) were independent influencing factors of the progression of gNET within 1 year. The regression equation was as below: P(Y)=1/[1+ e -(-0.934+0.047a+0.715b-2.597c)]. (a: tumor size, b: Ki-67 grading, c: undergoing the surgical resection of the primary lesion). Prediction grading was based on regression equation: 28 cases (29.2%) belonged to grade I(, 9 cases (9.4%) to grade II(, 24 cases (25.0%) to grade III(, and 35 cases (36.5%) to grade IIII(. The probability of progression within 1 year of patients in grade I(, II(, III( and IIII( was 10.7% (3/28),5/9, 58.3%(14/24), and 91.4%(32/35) respectively, with significant difference (χ=41.236, P=0.000). Prediction grading was positively correlated with the occurrence of tumor progression in gNEN patients within 1 year(r=0.644, P=0.000). The AUC of prediction grading to predict the progression of gNEN within 1 year was 0.857, while the sensitivity was 85.2% and the specificity was 69.0%. DeLong method was used to compare the AUC values of prediction grading, Ki-67 grading and TNM staging. Comparison result revealed that the predictive value of prediction grading was not significantly different with that of TNM staging (P=0.303), but was better than that of Ki-67 grading (P=0.006).

CONCLUSIONSOur grading standard can objectively and accurately reflect the probability of progression within one year in gNEN patients. The later the grading, the higher the probability of progression within 1 year is for gNEN patients.

Aged ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neuroendocrine Tumors ; pathology ; therapy ; ROC Curve ; Retrospective Studies ; Risk ; Sensitivity and Specificity ; Stomach Neoplasms ; pathology ; therapy