Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Objective To explore the correlation between social support and pregnancy depression in Shenzhen. Methods From August 2018 and June 2020, a structured questionnaire survey was conducted among pregnant women who underwent pregnancy examination in a 3A-grade maternal & child health care hospital. A total of 1 396 questionnaires with complete information were collected. Chi-square test and Wilcoxon rank sum test were used to analyze the baseline characteristics. The odds ratio (OR) and 95% CI confidence interval between social support and pregnancy depression were estimated using logistics regression model. Subgroup analysis was also conducted. Results There were statistically significant differences in education level, medical insurance rate, household registration, family monthly income, proportion of multiparas, proportion of husbands being the only child, pregnancy stress and social support between the depression group and non-depression group. After multi-factors adjustment, the OR (95% CI) of the total social support score was 0.97(95%CI 0.95-0.99), the OR (95% CI) of the objective support dimension was 0.90(95% CI 0.87-0.94), and the P value of the interaction term multiplied by pregnancy term was less than 0.05. According to the stratified analysis of pregnancy, the total score of social support was significantly correlated with the depression status only in the third trimester, with an OR (95% CI) of 0.97 (95% CI 0.94-0.99). The objective support dimension was significantly correlated with depression status in the first and third trimesters, and the OR (95% CI) was 0.78 (95% CI 0.61-0.99) and 0.89 (95% CI 0.84-0.94), respectively. The OR of support utilization score in the third trimester was 0.91 (95% CI 0.83-0.99). Conclusion Social support was negatively correlated with depression during pregnancy and was particularly important in the third trimester. Various dimensions of social support were differentially correlated with pregnancy depression in each trimester. The objective support dimension was particularly important in the first and third trimesters.

Objective:To explore the therapeutic effects and adverse reactions of the liposomal doxorubicin-based regimens in the treatment of adult patients with T-cell lymphoma.Methods:The clinical data of patients with T-cell lymphoma who were diagnosed and treated in Beijing Shijitan Hospital of Capital Medical University from August 2012 to May 2016 was retrospectively analyzed. All patients received chemotherapy containing liposomal doxorubicin. The clinical manifestations, treatment results, and adverse reactions were observed.Results:A total of 16 patients were enrolled, with a median age of 50.5 years old (16-81 years old), of which 7 patients were newly treated and 9 patients were retreated (including 5 refractory patients). Eleven of the 16 patients were evaluated for efficacy, including 4 cases of complete remission (CR) and 4 cases of partial remission (PR), the overall response rate was 72.8% (8/11). With a median follow-up of 11 months, the 2-year progression-free survival rate and overall survival rate were 42.4% and 41.6%. All 5 primary skin T-cell lymphoma patients were refractory or relapsed with 1 case of CR and 4 cases of PR after treatment. The adverse reactions were acceptable.Conclusions:The remission rate of liposomal doxorubicin-based regimens for treatment of adult patients with T-cell lymphoma is promising, especially for newly-treated patients. Primary skin T-cell lymphoma patients might be more likely to benefit from liposomal doxorubicin-based regimens.

Objective To establish the primary cat intestinal epithelial cells(IECs)culture methods and construct the cD-NA library for the following yeast two-hybrid experiment,so as to screen the virulence interaction factors among the final host. Methods The primary cat IECs were cultured by the tissue cultivation and combined digestion with collagenase XI and dispase I separately. Then the cat IECs cultured was identified with the morphological observation and cyto-keratin detection ,by using goat anti-cyto-keratin monoclonal antibodies. The mRNA of cat IECs was isolated and used as the template to synthesize the first strand cDNA by SMARTTM technology,and then the double-strand cDNAs were acquired by LD-PCR,which were subsequently cloned into the plasmid PGADT7-Rec to construct yeast two-hybrid cDNA library in the yeast strain Y187 by homologous recom-bination. Matchmaker?Insert Check PCR was used to detect the size distribution of cDNA fragments after the capacity calcula-tion of the cDNA library. Results The comparison of the two cultivation methods indicated that the combined digestion of colla-genase XI and dispase I was more effective than the tissue cultivation. The cat IECs system of continuous culture was established and the cat IECs with high purity were harvested for constructing the yeast two-hybrid cDNA library. The library contained 1.1× 106 independent clones. The titer was 2.8 × 109 cfu/ml. The size of inserted fragments was among 0.5-2.0 kb. Conclusion The yeast two-hybrid cDNA library of cat IECs meets the requirements of further screen research,and this study lays the foundation of screening the Toxoplasma gondii virulence interaction factors among the cDNA libraries of its final hosts.

Objective To explore the biological function of rhoptry protein 38(ROP38)of Toxoplasma gondii,and to iden?tify the reactogenicity of the recombinant protein(rROP38). Methods The ROP38 was amplified by RT?PCR from T. gondii RH strain,and was cloned into prokaryotic expression vector pET?28a(+). The recombinant plasmid was transformed into E. co?li BL21(DE3)competent cells. Then the rROP38 was analyzed by SDS?PAGE and identified by Western blot. Results SDS?PAGE showed that rROP38 was efficient expression with a molecular weight of about 43 kD. Western blot showed that rROP38 reacted with antibody of His tag or human positive antibody,which indicated that ROP38 had good reactogenicity and could be a serological diagnostic antigen. Conclusion The study successfully obtains the rROP38 of T. gondii with good reactogenicity.

Objective To develop a rapid molecular biological method for detection of the asymptomatic infection of Leish?mania. Methods Two pairs of primers named RV1?RV2 and K13A?K13B were selected to be the fast diagnosis primers since they were designed according to the conserved region of Leishmania kinetoplast DNA(kDNA)minicircles. The PCR amplifica?tion products of Leishmania donovani promastigote from Shandong Province were sequenced to compare their conservatism. The method was applied to detect 105 venous blood samples from healthy home canine and 7 venous blood samples from home canine suffered from Kala?azar in Heishui County of Sichuan Province,and 75 venous blood samples from susceptible population(no leishmaniasis symptoms)and 7 venous blood samples from patients in Xinjiang Kashi area in order to verify the feasibility and accuracy of the method. Results The size of PCR products was consistent with the expected fragments with high conservative among Leishmania species. The positive rates of 105 home canine samples and 75 susceptible population samples were 37.14%(39/105)and 82.67%(62/75)rspectively,and the positive rates of home canine suffered from Kala?azar and patients were all 100%(7/7). Conclusion This rapid diagnosis method is suitable for detection of asymptomatic infection of Leishmania in Kala?azar endemic areas of China with high sensitive and specific,thus it has bright perspective to be used.

Objective To construct a multi-gene recombinant pcDNA3-HBsAg-p30-ROP2 expression vector and identify it preliminarily. Methods According to recombinant pcDNA3-p30-ROP2 restriction sites,HBV HBsAg gene sequences of primers were designed and synthesized to amplify target fragment,and then cloned into pcDNA3-HbsAg-p30-ROP2 expression vector. Af-ter sequencing,it was identified finally by restriction enzyme digestion and other molecular biology techniques. Results HBV HBsAg gene segment was amplified by PCR and the multi-gene recombinant pcDNA3-HBsAg-p30-ROP2 expression vector was constructed and identified to be correct as theoretical values. The PCR and restriction enzyme digestion results showed that HBsAg and p30-ROP2 gene in recombinant plasmid were confirmed by DNA sequencing. Conclusion The multi-gene recombinant pcD-NA3-HBsAg-p30-ROP2 expression vector is successfully constructed.

Parathyroid carcinoma is a rare maligant tumor.The main clinical symptoms are primary hyperparathyroidism and all kinds of metabolism disorder and the damage of homologous tissues and organs.The consummate laboratory examination and the accurate imaging localization and the credible histopathologic feature are key points to diagnosis of parathyroid carcinoma.Parathyroid carcinoma is unsensitive to chemotherapy and radiotherapy,and en bloc resection of the carcinoma is the preferred treatment approach.AntiPTH immunization as a new treatment of parathyroid carcinoma has been paid close attention.The prognosis of parathyroid carcinoma is mainly depended on whether the tumor was cut off completely and the control as well as the monitor of the symptomatic hypercalcemian after operation.This article reviews the latest researches and introduces the latest advancement in the diagnosis and treatment of parathyroid carcinoma.

Objective To study the expression of secondary lymphoid-tissue chemokine (SLC)、 CCR7 and its correlation with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC). Methods The tissue specimens including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were obtained from 30 patients with PAC. The expressions of SLC and CCR7 in these tissues were assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR). MIND marked by VEGFR-3 was detected by morphometric analysis, and the relationship between MLND and clinical pathology of PAC was analyzed. Results In all the specimens, the positive rates of SLC protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 16. 7%, 43. 3%, 76. 7% and 46. 6%. The positive rates of CCR7 protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 76. 7%, 66. 7%, 30. 0% and 70. 0%. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CCR7 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lymph nodes were higher than that in the normal pancreatic tissues ( P <0. 01 ). There was no significant correlation between the expression of SLC protein with MLVD of PAC ( P > 0. 05 ). There was 23 specimens that the CCR7 protein was positive, and among these specimens the MIND was higher than that in negative group of CCR7 protein (P = 0.004). Conclusions The expression of SLC was not related to lymphatic metastasis and TNM stages of PAC. The expression of CCR7 was significantly associated with lymphatic metastasis and TNM stages of PAC, and the high expression of CCR7 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

Objective To analyze the intratumoral and peritumoral microvessel density (MVD) and microlymphatic vessel density (MLVD) in pancreatic cancer and record the expression of vascular endothelial growth factor(VEGF)-C and VEGF-D. And to explore the significance of VEGF-C and VEGF-D during the lymphatic metastasis and development of pancreatic cancer. Methods The expression of VEGF-C and VEGF-D, VEGF-R3, CD34 were assayed by immunohistochemical staining in 30 cases of pancreatic cancer tissues. Results The positive rates of VEGF-C and VEGF-D protein in the central portion of tumors (30% and 16.7%) were significantly lower than those in the marginal portion (73.3% and 56.7%), P <0.01. The group with high expression of VEGF-C and VEGF-D in the marginal portion had significantly higher incidences of lymph node metastasis, lymphatic invasion and venous invasion( P <0. 01 ). MLVD in both of the VEGF-C and VEGF-D positive groups was higher than that in the negative groups( P <0. 01 ), and the lymph node me-tastasis increased. MVD in VEGF-C positive group was significantly higher than that in the negative group. MVD had no significant difference between VEGF-D positive and negative group ( P =0. 07). Conclusions The expression of VEGF-C and VEGF-D in the marginal portion of tumor is significantly correlated with lym-phatic metastasis in pancreatic cancer patients, and may induce lymphangiogenesis. VEGF-C may play an im-portant role in the regulation of angiogenesis and lymphangiogenesis in pancreatic cancer, and VEGF- D maybe only participate in the regulation of lymphangiogenesis.