The predictive value of crescents in adult Henoch-Sch?lein purpura nephritis

Objective To study the renal prognosis with the type and proportion of crescentic in adult Henoch Schonlein purpura nephritis (HSPN). Methods A total of 275 HSPN cases diagnosed in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. According to the pathological results, they were divided into four groups: 99 patients in none crescent group (NC), 35 patients in segmental crescents group (SC), 122 patients with circumferential crescent ＜25% (C1), and 19 patients with circumferential crescent≥25% (C2). Renal prognostic events were defined as estimated glomerular filtration rate (eGFR) decreased by 30% over baseline within 2 years, doubling of serum creatinine or end-stage renal disease during follow-up. Kaplan-Meier survival analysis was used to compare the renal survival rate of each group. Univariate and multivariate Cox regression model was used to recognize the risk factor of poor renal outcome. Results There was no significant difference in age, extra renal organ performance and mean arterial pressure among groups. Among NC group, SC group, C1 group and C2 group, difference in serum creatinine (P=0.001), eGFR (P=0.003) and proteinuria levels (P＜0.001) were statistically significant. There was no significant difference in the ratio of global sclerosis, mesangial hypercellularity and interstitial inflammation/fibrosis among the groups. The patients were followed up for 86(58, 116) months. The renal survival rates of NC group, SC group, C1 group and C2 group were 96%, 100%, 83.6% and 68.4% respectively. Kaplan-meier survival analysis showed significant differences (Log Rank=23.24, P＜0.001). Cox multivariate regression analysis indicated that presence of circumferential crescent (HR=3.59, 95%CI 1.34-9.62, P=0.008) and low eGFR (HR=0.979, 95%CI 0.968-0.989, P＜0.001) were independent prognostic factors. Conclusion The presence of circumferential crescent and low eGFR level are independent risk factors for poor renal prognosis in HSPN patients.     

外泌体在胰腺癌中的研究现状与进展

外泌体是一种双层脂质膜连接囊泡样小体，存在于各种体液中，参与细胞及肿瘤微环境之间的物质运输和信号传递。外泌体含有多种生物活性分子，包括脂质、蛋白质、DNA、mRNA以及非编码RNA，可以通过这些活性分子影响肿瘤的发生和发展，甚至可以影响肿瘤的治疗。胰腺癌是一种常见的恶性肿瘤，侵袭性强，预后较差，死亡率高。胰腺癌来源的外泌体是胰腺肿瘤微环境中的重要组成部分，促使胰腺癌细胞成功逃避细胞凋亡的重要因素，并且可以促进肝脏转移微环境的形成。近年来，与胰腺癌相关的外泌体逐渐成为新的研究热点，研究发现外泌体有望成为早期胰腺癌筛查的新型生物学标志，并将为胰腺癌靶向治疗提供可行的技术基础。     

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3⁺ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3⁺ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3⁺ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8⁺/CD4⁺ T cells, reduced infiltration of regulatory FOXP3⁺ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3⁺ T cells in those with advanced GC.     

Cover Image,Volume 80, Issue 3

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real-time PCR were used to evaluate the expression level of the M₃ receptor, both TLR₃ and TLR₄ in uterine tissue, and the level of Ca²⁺ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M₃ receptor, TLR₃, TLR₄ expression, and the Ca²⁺ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs.

Diagnostic Value of Positive Findings of Toxoplasma gondii-Specific Immunoglobulin M Serum Antibody in Uveitis Patients to Confirm Ocular Toxoplasmosis

Purpose: To assess the value of positive immunoglobulin (Ig) M serum antibody (Ab) findings in uveitis patients.

Methods: We reviewed medical records of patients who had a positive serological test for Toxoplasma gondii-specific IgM Ab. Their clinical data, including history, demographic characteristics, laboratory findings, clinical findings, treatment outcomes, and recurrences, were reviewed retrospectively.

Results: Of 2919 uveitis patients who underwent a serological test for suspected ocular toxoplasmosis (OT), 18 presented with positive Ig M results. All 18 patients (100.0% specificity) were clinically diagnosed with OT. None had any retinochoroidal scar at the initial visit, indicating the OT was a recent and primary infection. However, 15 patients (83.3%) had no history suspected to account for the Toxoplasma transmission.

Conclusions: The T. gondii IgM serum Ab is a specific biomarker for diagnosis of primary OT. Epidemiological studies are warranted to investigate the non-classic transmission routes of T. gondii in OT.     

Variant analysis and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3

Objective To analyze the variants of 42 Chinese patients with Bartter syndrome type 3 (BS3) and explore the characteristics of genotype and phenotype. Methods Forty-two genetically diagnosed patients from 40 Han and one Hui families were collected in the Affiliated Hospital of Qingdao University and the Affiliated Qingdao Municipal Hospital of Qingdao University during the period of June 2012 to October 2018. The second-generation sequencing and multiplex ligase probe-dependent amplification (MLPA) technique were used to analyze the CLCNKB gene variation and its characteristics in children with BS3. The clinical data were collected, and the therapeutic effect and growth improvement were observed and followed up. Thirty eight patients were divided into severe (n=26) and light (n=12) groups according to the severity of genetic variation. The clinical phenotypic characteristics of the two groups were compared. Results Thirty-six variants including 16 novel ones of CLCNKB gene were found. The whole gene deletion of CLCNKB gene was the most frequent mutation (40%), and the rate of large deletions was up to 55%. The most common symptoms included development retardation (38/42), polydipsia and polyuria (35/42), constipation (31/42) and vomiting (27/42). All patients presented with hypokalemia, hypochloremia and metabolic alkalosis. After the medicine treatment that based on indomethacin and potassium chloride, most patients could achieve obvious recovery of growth rate and restoration of hypokalemia. The severe group showed more severe metabolic alkalosis than the light group. Conclusions Thirty-six variants of CLCNKB gene have been found in this study, including 16 novel ones, which enrich the human gene mutation database (HGMD) and provide valuable references to diagnosis, treatment and the genetic counseling of Chinese population.     

Discovery of structure-based small molecular inhibitor of αB-crystallin against basal-like/triple-negative breast cancer development in vitro and in vivo

αB-crystallin (CRYAB) is present at a high frequency in poor prognosis basal-like breast tumours, which are largely absent of oestrogen, progesterone receptors and HER2 known as triple-negative breast cancer (TNBC). CRYAB functions as a molecular chaperone to bind to and correct intracellular misfolded/unfolded proteins such as vascular endothelial growth factor (VEGF), preventing non-specific protein aggregations under the influence of the tumour microenvironment stress and/or anti-cancer treatments including bevacizumab therapy. Directly targeting CRYAB can sensitize tumour cells to chemotherapeutic agents and decrease tumour aggressiveness. However, growing evidence shows that CRYAB is a critical adaptive response element after ischemic heart disease and stroke, implying that directly targeting CRYAB might cause serious unwanted side effects. Here, we used structure-based molecular docking of CRYAB and identified a potent small molecular inhibitor, NCI-41356, which can strongly block the interaction between CRYAB and VEGF₁₆₅ without affecting CRYAB levels. The disruption of the interaction between CRYAB and VEGF₁₆₅ elicits in vitro anti-tumour cell proliferation and invasive effects through the down-regulation of VEGF signalling in the breast cancer cells. The observed in vitro anti-tumour angiogenesis of endothelial cells might be attributed to the down-regulation of paracrine VEGF signalling in the breast cancer cells after treatment with NCI-41356. Intraperitoneal injection of NCI-41356 greatly inhibits the tumour growth and vasculature development in in vivo human breast cancer xenograft models. Our findings provide ‘proof-of-concept’ for the development of highly specific structure-based alternative targeted therapy for the prevention and/or treatment of TNBC.