STAT3及相关生长调控基因在胃癌组织中的表达及意义

目的探讨转录信号传导子与激活子3（STAT3）及相关生长调控基因在胃癌发生发展中的作用及意义。方法应用RT—PCR检测STAT3基因及相关基因c—myc，p53，生存素（survivin），血管内皮生长因子（VEGF）的mRNA表达水平，应用Western印迹法及免疫组化法检测STAT3基因的蛋白水平及定位表达。结果胃癌组织及癌旁组织中STAT3 mRNA的表达均明显高于正常胃组织（P〈0．01），胃癌及癌旁组织中c—myc，surovivin，VEGF mRNA的表达上调（P〈0．01），p53 mRNA的表达下调（P〈0．01），胃癌组织及癌旁组织中STAT3蛋白水平的表达均高于正常胃组织（P〈0．01）。结论STAT3基因的持续激活在胃癌的发生发展中起重要作用，可作为早期诊断的指标及治疗的靶点。     

利用组织芯片技术研究PTEN和VEGF在胃癌中的表达及意义

目的研究PTEN和血管内皮生长因子（vascular endothelial growth factor，VEGF）在胃癌中的表达及临床意义。方法应用组织微阵列仪制作97孔胃癌组织芯片（tissue microarray）。用免疫组织化学S—P法检测PTEN、VEGF在72例胃癌和25例正常胃黏膜中的表达。结果胃癌组织中PTEN蛋白阳性表达率显著低于正常胃黏膜（45．8％ VS 100％，P〈0．01）；VEGF的阳性表达率显著高于正常胃黏膜（75％VSl2％，P〈0．01），PTEN在胃癌中的表达与VEGF呈负相关（P〈0．01）。PTEN、VEGF的表达在中高分化腺癌分别为68．8％、62．5％（P〉0．05），在低分化及未分化腺癌分别为27．5％、85．0％（P〈0．05）；伴淋巴结转移者分别为31．6％、86．9％（P〈0．05），无淋巴结转移者分别为61．8％、61。8％（P〉0．05）；临床病理分期Ⅰ＋Ⅱ期分别为57．1％、61．9％（P〉0．05），Ⅲ＋Ⅳ期分别为30．0％、93．3％（P〈0．05）；与性别、年龄、肿瘤大小和组织分型无显著差异（P〉0．05）。结论PTEN失活或蛋白表达降低、VEGF的高表达与胃癌临床病理特征和生物学行为有密切关系。PTEN在低分化或未分化以及伴淋巴结转移和临床Ⅲ＋Ⅳ期胃癌中的表达与VEGF呈负相关。联合检测PTEN、VEGF对胃癌的恶性程度及预后判断具有一定的临床参考意义。应用组织芯片大规模高效检测临床组织样本是可行的，具有快速、准确、方便经济的特点。     

胃癌组织中CTGF蛋白表达及其临床意义

目的探讨结缔组织生长因子（CTGF）蛋自在胃癌发生、发展中的作用。方法采用免疫组化法检测10份正常胃黏膜组织、50份胃癌组织及其癌旁组织中CTGF蛋白表达情况。结果胃癌组织中CTGF阳性表达高于癌旁组织及正常胃黏膜组织,P〈0．05;癌组织CTGF阳性表达率明显高于正常黏膜组织（P〈0．01）,CTGF的高表达与胃癌分化程度、淋巴结转移密切相关（P均〈0．05）;与肿瘤浸润的深度无明显关系。结论CTGF蛋白可作为胃癌前病变及胃癌早期诊断和预后判断的指标。     

胃癌组织中肝素酶和血管内皮生长因子-C的表达及其临床意义

目的探讨胃癌组织中肝素酶和血管内皮生长因子（VEGF）-C蛋白表达及其临床意义。方法采用免疫组化S-P法检测97例原发性胃癌组织、癌旁组织及20例正常胃黏膜组织中肝素酶和VEGFC蛋白的表达，并分析其与临床病理特征和预后的关系。结果胃癌组织肝素酶和VEGF—C蛋白表达阳性率分别为61．9％和66．0％，显著高于癌旁组织的7．2％和5．0％，正常胃组织的8．3％和5．0％（P值均〈0．01）；肝素酶表达与肿瘤分化程度无关，但与肿瘤直径、淋巴结转移、静脉侵犯、淋巴管侵犯、远处转移、浆膜面受累和TNM分期等密切相关；VEGF—C表达与肿瘤直径、分化程度、静脉侵犯及远处转移等无关，但与淋巴结转移、淋巴管侵犯、浆膜面受累和TNM分期等密切相关；肝素酶和VEGF—C阳性表达组术后生存率明显低于阴性组；在胃癌中肝素酶和VEGF—C阳性表达呈正相关。结论肝素酶及VEGF-C蛋白的阳性表达，可作为胃癌预后不良的参考指标。     

食管鳞癌组织中IGF-1R、VEGF-C的表达变化及意义

目的观察食管鳞癌组织中的胰岛素样生长因子-1R（IGF．1R）、血管内皮生长因子C（VEGF—C）的表达变化,并探讨其意义。方法分别采用免疫组化法、免疫印迹法检测食管鳞癌和癌旁正常食管组织中的IGF-1R、VEGF—C。结果食管鳞癌组织中IGF-1R、VEGF—C阳性率分别为81．05％、67．37％,癌旁组织中分别为20％、5％,P均〈0．01;食管鳞癌组织中IGF—IR、VEGF．C蛋白条带灰度比值分别为0．58土0．03、0．43±0．05,癌旁组织中分别为0．43±0．02、0．31±0．04,P均〈0．05。IGF—IR、VEGF—C表达与食管鳞癌淋巴结转移、浸润深度有关（P均〈0．01）,二者表达呈正相关（r=0．29,P〈0．05）。结论食管鳞癌组织中IGF—IR、VEGF—C高表达,在食管鳞癌的发生发展及转移中有重要作用。     

蛋白翻译起始因子C2在肝癌、胃癌中的表达与分布

目的 研究C2基因在肝细胞癌（HCC）、胃癌中的表达、分布及意义。方法 利用免疫组化法检测C2蛋白在60例HCC、58例胃癌组织中的表达，Western blot法检测C2蛋白在10例HCC及其癌旁组织中的表达。结果 60例HCC及42例癌旁组织中，C2蛋白阳性率分别为27．3％（17／60例）和83．3％（35／42例），C2蛋白在HCC癌组织中表达明显低于其癌旁组织（P＜0．001）；C2的表达与病人年龄、HBsAg及AFP明显关系（P＜0．05）。Western blot结果与免疫组化一致。在HBXAg阳性的49例HCC中，C2蛋白阳性率为20．4％，在HBXAg阴性的11例HCC中，C2蛋白阳性率为63．6％。C2在HBXAg阳性的HCC中的表达明显低于HBXAg阴性者（P＜0．05）。58例原发性胃癌及44例癌旁组织中，C2蛋白阳性率分别占41．4％（24／58例）和77．3％（34／44例）。C2蛋白在胃癌组织中表达明显低于其癌旁组织（P＜0．05），且与胃癌组织的分化程度、浆膜浸润、肿瘤大小有明显的关系（P＜0．05）。结论 C2基因表达下调可能与HCC、胃癌的发生、发展有关。HBXAg对C2的抑制作用可能与HCC的发生，发展有关。C2可能是一潜在的抑癌基因。     

Cx43和Fas在胃癌组织中的表达

目的研究间隙连接蛋白43（Cx43）和凋亡调节因子Fas在胃癌组织中的表达情况。方法应用免疫组化法检测70例胃癌患者手术切除的癌组织和癌旁正常组织中Cx43和Fas表达水平。结果Cx43在胃癌组织中的表达率为44．29％（31／70）,在癌旁正常组织中的表达率为92．86％（65／70）,P〈0．01;Fas在胃癌组织中的表达率为40．00％（28／70）,在癌旁正常组织中表达率为87．14％（61／70）,P〈0．01。Cx43表达水平与胃癌组织学分化程度、浸润深度、淋巴结转移有关（P〈0．05）,Fas表达水平与胃癌组织学分化程度、浸润深度、TMN分期、淋巴结转移有关（P〈0．05）。结论胃癌组织中Cx43和Fas表达水平的检测有助于判断胃癌的恶性程度。     

基质金属蛋白酶-2和环氧合酶-2在胃癌中的表达及意义

目的探讨环氧合酶-2（COX-2）和基质金属蛋白酶-2（MMP-2）在胃癌组织中的表达以及相互关系。方法收集外科胃癌手术患者30例，标本分别取自胃癌组织、癌旁3cm和6cm组织，同时取10例胃镜检查正常者的胃黏膜组织作为对照，用免疫组化法检测组织中COX-2和MMP-2蛋白的表达情况。结果30例胃癌组织中，26例COX-2表达呈阳性，而10例正常组织则无表达，两者间差异有统计学意义（P〉0．01）。30例胃癌组织中MMP-2的表达阳性率为83．33％（25／30），癌旁3cm组织为66．7％（20／30），癌旁6cm组织为3．3％（9／30），10例正常组织中仅2例有表达，癌旁6cm组织与正常组织比较差异无统计学意义（P〉0．05），胃癌和癌旁3cm组织与正常组织比较差异有统计学意义（P〈0．05）。在胃癌患者的癌旁3cm组织中，MMP-2、COX-2蛋白表达之间存在显著正相关（P〈O．01）。结论胃癌组织中有COX-2、MMP-2的高表达，且两者之间的表达强度具有等级相关性。COX-2蛋白可能通过诱导MMP-2蛋白的表达上调，增加胃癌细胞的侵袭力，从而成为其促进胃癌浸润、转移的途径之一。     

胃癌患者血清和组织IL-1β水平变化及临床意义

目的研究IL-1β与胃癌发生的相关性，探讨IL-1β在胃癌发生中的作用，为胃癌的防治提供新的思路。方法收集70例胃癌、45例癌旁和70例胃炎手术切除组织和胃镜下活检标本，采用免疫组化SABC法测定组织IL-1β蛋白表达水平；以双抗体夹心ELISA法测定胃癌、胃炎患者血清中IL-1β含量，并进行比较。结果胃癌患者血清IL-1β水平显著高于胃炎病人（P〈0．05），且与临床分期有关，进展期胃癌高于早期胃癌（P〈0．05）。IL-1β蛋白在胃癌、癌旁和胃炎中的表达率分别为65．95％、44．44％和22．50％；胃癌组IL-1β表达高于癌旁、胃炎组。低、未分化癌组织IL-1β的表达高于高、中分化癌组织（P〈0．05）；进展期胃癌高于早期胃癌（P〈0．05）。结论胃癌患者血清、胃粘膜组织中IL-1β表达高于胃炎组，提示胃粘膜IL-1β表达与胃癌的发生有一定的关系。     

Akt的活化对胃癌血管新生的促进作用

目的:研究Akt在胃癌及癌旁正常组织中的表达、活化状况及其与胃癌血管新生的关系.方法:收集手术切除的胃癌及相应的癌旁正常组织标本48例.采用Western blot法检测20例新鲜胃癌及癌旁组织Akt和磷酸化Akt(pAkt)蛋白的表达.以免疫组织化学法检测pAkt蛋白在48例胃癌和癌旁正常组织的表达以及血管内皮生长因...     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.