B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors

The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function.     

红外多波长无创人体血糖检测阵列模型的研究

无创血糖监测不仅可以减少患者的痛苦，还能进行连续测量，从而降低并发症的发生，它是一种不需收集血样进行体内血糖浓度测量的新技术。本文根据朗伯-比尔定律(The Lambert—Beer Law)原理，为克服无创血糖检测研究中的难点和缺陷，详细分析了血糖红外光谱的吸收特性，利用阵列技术设计了红外多波长无创血糖检测传感器阵列模型，对关键技术进行了讨论。用ME算法建立了信号检测和标定数学模型，结合了人体各种影响因素，使红外无创血糖检测的精度和稳定性得到了改善。列举了详细的实验实施步骤，同时叙述了系统调试的详细过程，讨论了无创血糖检测中需要注意的问题。     

Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. Histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. Immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.     

Synchronous ileal and colonic adenocarcinomas associated with Crohn's disease: report of a case with a focus on genetic alterations and carcinogenesis

Patients with Crohn's disease have an increased risk of developing intestinal tumours. However, the carcinogenic mechanisms remain poorly understood. To address this question, this report describes an unusual case of Crohn's disease complicated by synchronous small intestinal and colonic adenocarcinomas. Genetic events in both the tumours and their adjacent mucosae were evaluated and the tumorigenesis of these cancers is discussed.     

Association of genetic polymorphisms and haplotypes in hMLH1 and hMSH3 gene with the risk of papillary thyroid carcinoma

OBJECTIVE: To explore the relationship of the genetic polymorphisms and the haplotypes in hMLH1 and hMSH3 gene with the risk of papillary thyroid carcinoma (PTC) in Chinese Hans. METHODS: A hospital based 1:1 matched case-control study was carried out. The polymorphisms for 204 pairs of PTC cases and healthy controls were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific oligonucleotide (PCR-ASO) assays. RESULTS: (1) The PTC risk was marginally increased in the hMLH1 1151TA genotype, with odds ratio (OR) of 2.15 (95%CI: 0.99-4.85); the PTC risk was significantly increased in the mutant genotype 1151TA+AA, with OR of 2.15 (95%CI: 1.02-4.69); (2) The haplotypes of -93G, 1151A, 655A in the hMLH1 gene could increase the PTC risk, with OR of 2.67 (95%CI: 1.16-6.53, P=0.011), compared with the haplotype of -93G, 1151T, 655A; (3) Compared to 3124A, 2835G haplotype in hMSH3 gene, the 3124G, 2835A haplotype could increase the PTC risk marginally, with OR of 3.08 (95%CI: 0.92-13.25). CONCLUSION: The 1151T/A polymorphism in hMLH1 was associated with PTC; both the haplotype of -93G, 1151A, 655A in hMLH1 and the 3124G, 2835A haplotype in hMSH3 were associated with PTC.     

不同造模方法所致“热毒血瘀证”模型家兔血液流变学改变的比较研究

本文通过金葡菌、大肠杆菌内毒素、地塞米松加内毒素等三种不同的攻毒方法复制了“热毒血瘀证”的动物模型。结果提示三种模型在血凝学指标上均表现为KPTT、PT明显缩短,而在血液流变学指标上则有不同。金葡菌所造模型表现为明显的高粘状态,内毒素模型则表现为明显的低粘状态,地塞米松加内毒素模型则改变不明显。     

Age-related changes in the response to vasoconstrictor and dilator agents in isolated beagle coronary arteries

Summary Responses to vasoactive agents were compared in helical strips of coronary arteries isolated from beagles of 30 days, 3 months, 2 years and 12 years old. Serotonin contracted the arterial strips dose-dependently, the contraction being greater in the arteries of proximal portion than in the distal arteries. The contraction increases with age from 3 months to 12 years, although EC50 values did not differ. Angiotensin II contracted distal coronary arteries to a greater extent than the proximal ones. Age did not alter the peptide-induced contraction. In prostaglandin F₂-contracted coronary arteries, acetylcholine-induced relaxations, dependent on endothelium, were less in the arteries from senescent beagles than in those from adult beagles (2 years old). Histamine relaxed the infant beagle arteries to a lesser extent than the adult and senescent beagle arteries. Histamine-induced relaxations were attenuated selectively by cimetidine. Relaxations caused by adenosine and prostaglandin I₂ did not differ in coronary arteries from beagles of different ages. It may be concluded that greater responsiveness to serotonin of senescent beagle coronary arteries is due preferentially to increased function of serotonergic receptors rather than impaired function of the arterial endothelium responsible for the release of relaxing factor(s), although some impairment of the function is supposed, on the basis of interferences with acetylcholine-induced relaxation in the aged beagle arteries. Histaminergic H₂ receptor function appears to develop in beagle coronary arteries until 3 months of age. Send offprint requests to N. Toda     

Correction to: Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia

The study of sex differences in hyperuricemia can provide not only a theoretical basis for this clinical phenomenon but also new therapeutic targets for urate-lowering therapy. In the current study, we aimed to confirm that estradiol can promote intestinal ATP binding cassette subfamily G member 2 (ABCG2) expression to increase urate excretion through the PI3K/Akt pathway. The estradiol levels of hyperuricemia/gout patients and healthy controls were compared, and a hyperuricemia mouse model was used to observe the urate-lowering effect of estradiol and the changes in ABCG2 expression in the kidney and intestine. In vivo and in vitro intestinal urate transport models were established to verify the urate transport function regulated by estradiol. The molecular pathway by which estradiol regulates ABCG2 expression in intestinal cells was explored. The estradiol level of hyperuricemia/gout patients was significantly lower than that of healthy controls. Administering estradiol benzoate (EB) to both male hyperuricemic mice and female mice after removing the ovaries confirmed the urate-lowering effect of estradiol, and hyperuricemia and estradiol upregulated the expression of intestinal ABCG2. Estradiol has been confirmed to promote urate transport by upregulating ABCG2 expression in intestinal urate excretion models in vivo and in vitro. Estradiol regulates the expression of intestinal ABCG2 through the PI3K/Akt pathway. Our study revealed that estradiol regulates intestinal ABCG2 through the PI3K/Akt pathway to promote urate excretion, thereby reducing serum urate levels.     

The Protective Roles of Exercise and Maintenance of Daily Living Routines for Chinese Adolescents During the COVID-19 Quarantine Period

PurposeAdolescents are particularly vulnerable during the COVID-19 quarantine periods and may be at risk for developing psychological distress symptoms that extend beyond a crisis, including depression. This study examined adolescents’ postquarantine depressive symptoms associated with pandemic stressors. The primary aim was to identify potential protective factors that may buffer the association between the presence of COVID-19 cases in adolescents’ communities and their postquarantine depressive symptoms.MethodsAdolescents from public schools were recruited from Zhengzhou city, Henan, China (N = 1,487, M_age=13.14 years, 50% girls). Adolescents reported the presence of confirmed or suspected COVID-19 cases in their communities, their daily activities and routines during the 2-month quarantine period, and depressive symptoms after the quarantine period.ResultsThe presence of cases in adolescents’ communities during the quarantine contributed to more depressive symptoms in adolescents after the quarantine. This association was buffered by adolescents’ spending more time on physical activities and better maintenance of daily living routines during the quarantine period. The presence of community infection was also more strongly associated with depressive symptoms in older adolescents.ConclusionsThe presence of COVID-19 cases in communities contributed to adolescents’ poorer mental health, and the association was stronger for older adolescents. Spending time on physical activities and maintaining daily living routines during the quarantine appear to be practical strategies that can be used by adolescents to mitigate the association between pandemic stressors and their diminishing mental health.