1,25-(OH)2维生素D3对NOD小鼠的免疫干预作用

目的　探讨 1,2 5 (OH) 2 维生素D3 〔1,2 5 (OH2 )D3 〕对环磷酰胺促发的NOD小鼠 1型糖尿病的预防作用。方法　取体重相近的 4周龄NOD雌性小鼠 2 0只在实验开始前均一次性腹腔注射环磷酰胺 2 80mg/kg以加速胰岛炎。分为两组 ,每组 10只 ,干预组隔日腹腔注射 1,2 5 (OH2 )D3 5 μg/kg ,对照组注射等量的花生油。 3 0天实验结束时 ,观察糖尿病发生率 ,行HE染色观察胰岛炎程度 ,免疫组化观察bcl 2 ,bax在胰岛的表达 ,流式细胞仪定量测定脾脏T淋巴细胞的凋亡率。结果　 1,2 5 (OH) 2 D3 干预组糖尿病发病率较花生油对照组发病率低 ;1,2 5 (OH) 2 D3 干预后血糖值较干预前显著下降 (P <0 .0 1) ;干预组胰岛炎严重程度较花生油对照组明显减轻 ;胰岛细胞抑制凋亡的bcl 2基因的表达在 1,2 5 (OH ) 2 D3 处理组高于花生油对照组 ,而促进凋亡的bax基因的表达在 1,2 5 (OH ) 2 D3 组低于花生油对照组 (均P <0 .0 5 ) ;1,2 5 (OH ) 2 D3 组脾淋巴细胞凋亡率为 (3 2 .3 1± 7.0 1) % ,而花生油对照组凋亡率为 (2 4.19± 7.70 ) % (P <0 .0 5 )。结论　 1,2 5 (OH) 2 D3 对环磷酰胺加速的NOD小鼠胰岛具有保护作用。     

T淋巴细胞亚群及维生素D水平与衰老的关系

目的探讨随年龄增长T淋巴细胞表型、血清25-羟维生素D[25-(OH)D]水平变化的规律。方法将216例健康体检对象按年龄分成3组,组1为非老年组(18~60岁)85例,组2为非高龄老年组(61~80岁)76例,组3为高龄组(>80岁)55例;均采用四色免疫荧光标记流式细胞术分析外周血T淋巴细胞亚群、化学发光分析仪测定血25-(OH)D水平。结果 (1)各年龄组外周血T淋巴细胞亚群CD4~+、CD8~+都在正常范围内,组间无统计学差异(P>0.05)。组1 CD3~+明显高于组2和组3(P<0.05)。(2)组1CD95阳性明显高于组2和组3(P<0.05)。(3)组2血清25-(OH)D水平明显低于组1和组3(P<0.05)。(4)血清25-(OH)D水平与年龄呈负相关(r=-0.021,P<0.05),与T细胞亚群CD95呈正相关(r=0.17,P<0.05)。结论随着年龄增长T淋巴细胞亚群CD4~+、CD8~+变化不明显,CD3~+明显下降,CD95表达水平逐渐增高,而血清25-(OH)D逐渐降低,提示D95、25-(OH)D有可能成为评价免疫衰老潜在的生物学标志物。     

桥本甲状腺炎小鼠中性粒细胞胞外捕获网与T细胞分化相关性及维生素D的缓解作用

目的探讨实验性自身免疫性甲状腺炎(EAT)小鼠中性粒细胞胞外捕获网(NETs)与T淋巴细胞的相关性及活性维生素D的干预作用。方法 6周龄雌性BALB/c小鼠分为对照组、EAT组和骨化三醇干预组(VitD组;n=6/组)。HE染色观察甲状腺病理, ELISA法检测血浆甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)、1, 25(OH)2D3;流式细胞术检测外周血NETs形成率、脾脏Th1、Th2及Th17细胞比例;分析NETs形成率与Th1、Th2、Th17细胞比例的相关性。结果与对照组相比, EAT组甲状腺炎症评分、发病率、TPOAb、TGAb、NETs形成率、Th2(CD4+IL-4+或CD4+IL-13+)和Th17细胞比例显著升高(P分别<0.001、0.002、0.007、<0.001、<0.001、0.003、0.001、0.002), 1, 25(OH)2D3水平、Th1细胞比例、Th1/Th2(CD4+IL-4+)、Th1/Th2(CD4+IL-13+)、Th1/Th17比值显著降低(P分别0.010、0.018、0.010、0.005、...     

HIV/AIDS病人CD+4T淋巴细胞Th1型与Th2型变异分析

目的 研究艾滋病(AIDS)病人、艾滋病病毒(HIV)感染者、健康人群的Th1/Th2淋巴细胞亚群平衡漂移.方法 胞外CD分子染色和胞内细胞因子染色相结合,应用流式细胞术分析CD 4T淋巴细胞的Th1/Th2亚群百分比.结果 3组人群在CD 4T淋巴细胞计数、Th1细胞百分比、Th2细胞百分比3个指标的分布上,均表现出显著性差异(P＜0.001).正常人群和HIV/AIDS病人在Th1和Th2细胞百分比分布上,均未表现出显著性差异(P＝0.067,P＝0.835).艾滋病病人Th1型细胞百分比的均值在治疗过程中呈阶梯状上升趋势,其与治疗时间在68周内的回归系数为0.741,但无统计学意义(r＝0.741,P＝0.057);Th2细胞百分比的均值在治疗过程中呈明显的下降趋势,其与治疗时间在68周内的回归系数为0.847,有统计学意义(r＝0.847,P＝0.016).结论 监测CD 4T淋巴细胞Th1/Th2亚群漂移,对于了解艾滋病病人免疫功能变化,认识艾滋病发展规律有重要意义.     

雷帕霉素对1型糖尿病小鼠免疫功能的影响及其分子机制

目的研究雷帕霉素对1型糖尿病（T1DM）小鼠的影响及其分子机制。方法40mg／kg的STZ腹腔注射C57BL／6小鼠连续5d建立T1DM模型,正常和T1DM小鼠按2mg／kg腹腔注射RAPA连续两周。监测血糖、体重、进食量和饮水量;观测胰岛炎、主要脏器的超微结构和凋亡和自噬的发生;检测脾脏Th1／Th2分群和调节性T细胞。结果RAPA对正常小鼠一般特性及主要脏器的超微结构无明显影响。但可使T1DM小鼠血糖升高、体重下降、采食和饮水量增加（P〈0．05）,并加重其胰岛炎程度;诱导其胰腺、肾脏、脾脏和胸腺细胞自噬或凋亡,并使LC3、Beclin1、Caspase-3的表达增加;减少正常和T1DM小鼠的Th1细胞,增加Th2细胞,并上调CD4^＋CD25%＋T细胞的数量。结论RAPA既可诱导免疫耐受,发挥免疫抑制作用,又可通过自噬直接破坏胰岛从而加重T1DM代谢紊乱和并发症。     

维生素D与1型糖尿病

1，25(OH)2D3及其类似物均可抑制非肥胖糖尿病(NOD)鼠1型糖尿病的发生，而且后者可以避免1，25(OH)2D3对血钙和骨代谢的副作用。其作用机制可能为1，25(OH)2D3通过维生素D受体(VDR)抑制树突状细胞(DC)s的成熟及分化，使其白介素(IL)-12表达减少，激活Th1细胞的能力下降，纠正Th1／Th2的失衡，导致Th1型细胞因子干扰素—γ、IL—2分泌减少，使胰岛β细胞破坏减少，从而抑制1型糖尿病的发生。     

IL—4对NOD小鼠1型糖尿病免疫干预及其机制的探讨

目的：探讨IL－4对NOD鼠1型糖尿病发病率，胰岛炎的影响及其机制。方法：采用人类1型糖尿病动物模型NO（nonobese diabetic)鼠，IL－4处理后检测血糖，尿糖及糠愕病发病率，HE染色观察胰岛炎程度，流式细胞仪测定周围及中枢淋巴细胞亚群的变化，结果IL－4处理组糖尿病发病率为12．50％，明显低于对照组（62．50％）（P＜0．05），且胰岛炎的严重程度亦低于对照组；处理组周围单个核细胞（CD 4/CD 8及IL－2R＋细胞百分比增高，胸腺CD＋4，CD＋8细胞百分比增高而D＋4 CD＋8细胞百分比下降（P＜0．01）。结论 IL－4有降低NOD鼠1型糖尿病发病率及胰岛炎严重程度的作用，这种作用可能与IL－4影响了淋巴细胞亚群的分布从而纠正了免疫调节失衡有关。     

维生素D与自身免疫性糖尿病

维生素D对于自身免疫性糖尿病包括1型糖尿病、成人迟发型自身免疫性糖尿病及同种系胰岛移植后再发的糖尿病的发生和发展有预防或治疗作用，并且1型糖尿病的发病与维生素D的缺乏、血清低维生素D水平及维生素D受体基因多态性有关。有研究发现，在自身免疫性糖尿病动物模型非肥胖糖尿病(NOD)鼠中使用1，25(OH)2D3可以阻止或减少胰岛炎的发生率，降低其自发性糖尿病的发病率。维生素D预防或治疗自身免疫性糖尿病的可能机制是调节免疫细胞如辅助性T细胞、树突状细胞、调节性T淋巴细胞的活性，并且对胰岛细胞和免疫细胞的凋亡有一定的影响。     

口服胰岛素预防昆明株小鼠免疫性糖尿病的机理

目的　探讨口服胰岛素预防链尿菌素 (STZ)引起的胰岛炎及糖尿病的机理。　方法　正常昆明株小鼠 2 0只随机分为 2组 ,实验组 ,口服猪胰岛素 1mg,2次 /周 ;对照组 :口服等量的蒸馏水。 10周后 2组小鼠均腹腔注射STZ 4 0mg·kg-1·d-1× 5d。以血糖≥ 16 .7mmol/L诊断为糖尿病。监测 2组小鼠的血糖 6周。 6周后处死 2组小鼠 ,观察胰岛与脾内T细胞亚群及Fas/FasL的表达。　结果　 6周后实验组发病率为 0 % ;对照组为 90 % (P <0 .0 1) ,胰岛炎的评分实验组为 0 .0 6± 0 .19,对照组为 2 .5 4±0 .2 9(P <0 .0 1)。对照组胰岛内浸润的T细胞以CD8+为主 ( 5 9% ) ;而实验组以CD4+为主 ( 73% )。组织学检查示 :对照组胰岛 β细胞数显著减少 ,且 β细胞上出现Fas表达 ;而实验组胰岛 β细胞数显著多于对照组 ,实验组 90 %小鼠显示正常胰岛结构 ,β细胞上未见Fas表达 ;而两组胰岛内浸润T细胞均有FasL表达。　结论　口服胰岛素可抑制CD8+T细胞在胰岛局部的聚集及 β细胞表达Fas,避免FasL( + )T细胞引起的 β细胞凋亡 ,从而预防了糖尿病的发生。     

T细胞接种对环磷酰胺处理NOD小鼠糖尿病的影响

目的 探讨T细胞接种（TCV）对Ⅰ型糖尿病的预防作用。方法 将6周龄未发病的雌性NOD鼠用4周龄未发病、18周龄新近发病和32周龄发病时间长的NOD鼠脾细胞制得的T细胞疫苗接种,检测TCV对环磷酰胺处理的NOD鼠糖尿病发病率和胰岛炎程度的影响,以及接种后宿主淋巴细胞亚群的变化情况。结论 TCV可以降低糖尿病发病率、减轻胰岛单个核细胞的浸润程度,诱导宿主脾脏CD8^ T细胞百分比升高、CD4^＋／CD8^ 比值和IL－2R^ 细胞下降,胸腺CD4^- CD8^-单阳性细胞百分比升高。结论 TCV可降低宿主对自身免疫的反应性,这种作用可能与宿主脾脏、胸腺淋巴细胞亚群的变化和对糖尿病的预防效应有关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

CagA-Hp抗体IgG与胃炎的组织学分析

研究幽门螺杆菌(Hp)感染与胃炎的关系。方法对204例慢性胃炎患者胃粘膜进行观察分析,并测定其中137例Hp阳性患者血清CagA-Hp抗体IgG水平,与组织学对照。结果慢性萎缩性胃炎伴肠上皮化生患者血清CagA抗体IgG明显高于对照组(P＜0.01);其他类型胃炎患者血清CagA抗体IgG水平无明显增高(P＞0.05)。结论CagA-Hp可能是导致慢性萎缩性胃炎伴肠上皮化生的因素之一,对这类患者应密切随访观察。     

慢阻肺急性加重期患者预后的影响因素分析

目的探讨慢性阻塞性肺病急性加重期(AECOPD)患者预后的相关危险因素。方法回顾性调查、收集58例AECOPD患者可能影响其预后的相关因素,并对其分别进行单因素分析。并进行Logistic多元逐步回归进行多因素分析,筛选影响AECOPD患者预后的独立危险因素。结果单因素分析后将结果 P0.1的因素纳入多因素Logistic回归,分析发现是否合并呼吸衰竭、气促程度、白细胞计数、APACHEⅡ、应用抗氧化剂、慢阻肺治疗依从性为影响AECOPD患者预后不佳的独立因素(P0.05)。结论根据AECOPD患者预后的独立危险因素,及早判断,选择合适的后续治疗方案,对提高其生存率及生存质量具有重要意义。     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

Results of treatment of fistula-in-ano

To evaluate the application of Parks' classification in the management of patients with fistula-in-ano, a study was undertaken to assess the outcome of surgery, especially with respect to the recurrence rate and alteration of continence. A retrospective analysis of 160 consecutive patients who were classified at the time of operation was conducted. The distribution of fistulas was as follows: intersphincteric, 41.9 percent, transsphincteric, 52.1 percent, suprasphincteric, 1.3 percent, extrasphincteric, 0. A horseshoe extension occurred in 8.8 percent of the fistulas and 3.8 percent did not exactly conform to the classification as they were either complex or combinations of more than one type of fistula. The sole immediate postoperative complication was bleeding, which occurred one week postoperatively and ceased spontaneously (0.7 percent). Alteration in continence occurred in 6 percent of patients with 2.6 percent experiencing temporary incontinence to flatus, 1.3 percent to liquid stool, and 0.7 percent to solid stool. Permanent loss of control for flatus occurred in one patient (0.7 percent) and for liquid stool in one patient (0.7 percent). No patients suffered loss of control for solid stool. Recurrence developed in 6.3 percent of patients, all between five and 25 months postoperatively. Classifcation was found to be a useful guide in the operative management of patients with fistula-in-ano. Read at the joint meeting of the American Society of Colon and Rectal Surgeons with the Section of Colo-Proctology, Royal Society of Medicine, and the Section of Colonic and Rectal Surgery, Royal Australasian College of Surgeons, New Orleans, Louisiana, May 6 to 11, 1984.     

Intake of energy drinks in association with alcoholic beverages in a cohort of students of the School of Medicine of the University of Messina

BACKGROUND: Energy drinks (ED) are a widely used group of beverages known for their stimulant effects on central nervous system (CNS). The main components of ED are caffeine, taurine, carbohydrates, glucuronolactone, inositol, niacin, pantenol, and beta-complex vitamins. The studies evaluating the effects of ED describe improvements in attention and/or reaction times and indices of alertness. It has been also shown that combination of caffeine and glucose, fundamental constituents of ED, can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand. Moreover, the associated ingestion of alcohol and ED has recently been observed to be becoming more and more widespread. METHODS: With the aim to know the habits and uses of students, we administered a questionnaire containing questions regarding ED drinking alone or in association with alcoholic beverages. Five hundred students of the School of Medicine of the University of Messina were interviewed, and 450 filled the questionnaire. RESULTS: A total of 56.9% of students declared using ED. A great part of users (48.4%) associate frequently ED and alcohol. In particular, 35.8% of ED + alcohol users have used ED + alcohol more than 3 times in the last month. Distinguishing the users into 2 groups (users of ED + alcohol and users of both ED and ED + alcohol), we observed in the second group a major use of cocktail containing a mix of ED and alcoholic beverages. This difference between the 2 groups is less represented about the ingestion of ED + alcohol in the night. CONCLUSIONS: Our data indicate that association of ED + alcohol is very popular among students. This behavior can be dangerous. In fact, the combination of ED + alcoholic drinks can reduce adversive symptoms of alcohol intoxication including the depressant effects. As consequence, users of ED + alcoholic beverages might not feel the signs of alcohol intoxication, thus increasing the probability of accidents and/or favoring the possibility of development of alcohol dependence.