Analysis of characteristics of pedigrees with von Hippel-Lindau disease / 中华泌尿外科杂志

Objective To discuss the clinical characteristics of yon Hippel-Lindau (VHL)syndrome and the significance of genetic test for this disease.Methods Patients with VHL disease from 3 different families were reviewed from August 1985 to October 2017.The study was including clinical family survey and VHL-gene test on phylogenetic level.Totally 21 family members from 3 families were investigated,consisting of 14 males and 7 females with average age of 48.6 (5-70)years when analyzed.There were 8 patients with VHL disease comprising 5 males and 3 females with average onset age of 31.5 (9-67) years.Results The proband of pedigree one (VHL-Ⅱ C) was diagnosed as pheochromocytoma (PHEO) of right adrenal gland at 18 years old and underwent adrenalectomy,and her son was diagnosed with PHEO of bilateral adrenal glands with diagnostic age of 9 years old and received bilateral adrenalectomy sequentially.Her niece was diagnosed as PHEO of bilateral adrenal glands at 28 years old and received bilateral adrenal-sparing surgery simultaneously.Genetic analysis revealed a heterozygous mutation located at the third exon of the VHL gene (c.482G ＞ A).The proband of pedigree two (VHL-Ⅱ B) was diagnosed as right PHEO,bilateral multiple renal clear cell carcinoma (RCC),multiple pancreatic cysts and bilateral epididymal cystadenoma,and he received right adrenalectomy,right partial nephrectomy at 25 years old and delayed eystadenoma excision.His younger brother was also diagnosed as bilateral,pancreatic multiple cysts and bilateral epididymal nodules at 27 years old,and underwent right radical nephrectomy.Genetic analysis revealed a heterozygous mutation located at the first exon of the VHL gene (c.233A ＞ G).The proband of pedigree three (VHL-Ⅱ B) was diagnosed with central nerve system hemangioblastomas (CNS-HB) at 35 years old and received external beam radiotherapy.His elder sister was diagnosed as CNS-HB at 43 years old and received surgery.His father was diagnosed as right PHEO,bilateral RCC,bilateral multiple renal and pancreatic cysts and pancreatic neuroendocrine tumors at 67 years old.He received right adrenalectomy and partial nephrectomy.Genetic analysis showed a heterozygous mutation located at the third exon of the VHL gene(c.500G ＞ A).In addition,two cases (F2-Ⅲ 1 and F3-ⅣV1) were found to be asymptomatic VHL gene carriers by genetic screening.8 patients were followed up for an average of 9.8 (2-32) years.The symptoms were stable and no local recurrence or distant metastasis was found after operation.In this study,no CNS-HB was found in patients within family 1 and family 2,and RCC in 3 patients within family 2 and family 3 were low grade.Conclusions The clinical manifestations of VHL disease are diverse.RCC and CNS-HB are not present in all patients with the disease.PHEO is the only manifestation in patients with VHL-ⅡC.It is necessary to inform the members of VHL syndrome family for genetic test.Genetic test combined with clinical screening can facilitate differential diagnosis for VHL syndrome and other hereditary urological diseases.

Multiple endocrine neoplasia type 2A caused by a p.C618R RET proto-oncogene mutation in a Chinese pedigree / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A).</p><p><b>METHODS</b>Comprehensive medical history was obtained for 5 members from a 3-generation family from southern China. Clinical investigations have included biochemical testing, imaging, and screening of germline RET proto-oncogene mutations.</p><p><b>RESULTS</b>Genetic screening has revealed a missense mutation at codon 618(TGC>CGC) of exon 10 in 3 patients(p.C618R), which was consistent with their clinical manifestations. For the 3 individuals, the age at diagnosis was 21, 26 and 36 yr, and the maximum diameter of medullary thyroid carcinoma was 22, 25 and 39 cm, respectively. The 36-year-old female patient initially underwent right total thyroidectomy plus right neck lymph node dissection. Four years later, she again underwent left adrenal tumorectomy and left total thyroidectomy plus left neck lymph node dissection. The 21-year-old male patient underwent right total thyroidectomy plus right modified neck dissection. The follow-up was respectively 146 and 26 months following the initial operation. Two patients still presented elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid masses on imaging examination. The 26-year-old female patient, who presented bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy.</p><p><b>CONCLUSION</b>Combined family survey and RET gene screening can facilitate early diagnosis and surgical treatment to improve the prognosis.</p>

Pedigree screening of a Chinese multiple endocrine neoplasia type 2A family and prophylactic total thy-roidectomy / 中华内分泌外科杂志

Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A(MEN 2A)family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma ( MTC).Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members(p.C634R), which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years(ranging from 19 years to 65 years) and the mean maximum diameter of MTC was 2.3 cm(ranging from 0.7 cm to 5.2 cm). Among them 3 members had palpable neck masses (1 case with diarrhea).Right total thyroidectomy +right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy +bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy +bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom ( PHEO) underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient( T3N 1bM 0-1) underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively (T1N 1bM0 and T2N 1bM0), and the other one patient was closely monitored and followed up for 22 months(T2N 1b M0).Moreover, The calcitonin levels dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .

Quantum Dots Labeled Lateral Flow Strip for Determination of Procalcitonin in Blood / 分析化学

CdSe/ZnSquantumdots(QDs)werepreparedandcovalentlylinkedtoanti-katacalcinmonoclonal antibodies. After modification, the QDs' maximum emission wavelength was shifted to 625 nm from 620 nm while maintaining the spectral properties. Then the QDs labeled lateral flow strip and corresponding fluorescence measuring instrument were designed and fabricated. To reduce the cost of strip by reducing the amounts of monoclonal antibodies, appropriate amounts of QDs labeled monoclonal antibodies were sprayed on the conjugation pad, with just one test line on the strip but without the control line. Parameters of the strip were optimized by measuring the signal to noise ratio. By using the strip and fluorescence measuring instrument, procalcitonin (PCT) could be detected in 20 min, and the quantitative detection range was 0. 2-100 μg/L with sensitivity of 0. 1 μg/L. A total of 22 blood samples were measured by both our method and the commercial instrument used in the hoptital. The results were consistent for their Pearson correlation coefficient (0. 9995) and Kolmogorov-Smirnov test (Sig=1. 0). The rapid quantitative detection method for PCT is of great importance to quantitative detection of bacterial infection and rational usage of antibiotics clinically.

Changes of semen quality in uremia patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the changes of the semen quality in uremia patients before renal transplantation.</p><p><b>METHODS</b>The semen of 24 patients with uremia and 12 normal volunteers was analyzed.</p><p><b>RESULTS</b>The semen volume, sperm motility, survival rate, density and morphological normality percentage were (2.5 +/- 0.4) ml, (13.4 +/- 3.9)%, (25.4 +/- 5.6)%, (20.6 +/- 4.5) x 10(6)/ml and (16.8 +/- 2.1)%, respectively, significantly lower than those of the normal group (P < 0.01).</p><p><b>CONCLUSION</b>Semen qualities were lowered significantly and spermatogenesis severely affected in patients with uremia.</p>

Verapamil modulates LPS-induced cytokines production via inhibiting NF-?B activation in the liver of rats / 肠外与肠内营养

Objective:To investigate the effect of verapamil on the endotoxin-induced cytokine production and nuclear factor kappa B(NF-?B) activation in the liver. Methods:Fifty six adult male Sprague-Dawley rats were randomly divided into seven groups: group A: saline;group B:endotoxin(10 mg/kg,intraperitoneally,i.p.);group C,D,E,F:endotoxin(10 mg/kg) after treatment with verapamil(1,2.5,5,10 mg/kg i.p.respectively),and group G:verapamil alone(10 mg/kg).Tumor necrosis factor(TNF-?),interleukin-6(IL-6), interleukin-10(IL-10) and NF-?B in the liver tissues and the serum levels of ALT and AST were investigated at 1 h afer LPS injection. Results:Endotoxin stimulated production of TNF-?,IL-6 and IL-10,and activated NF?B in the liver.Verapamil attenuated acute liver injury,down-regulated endotoxin-induced pro-inflammatory cytokine production,up-regulated ant-inflammatory cytokines production and inhibited NF-?B activation in the liver in a dose-dependent manner.Conclusion:Verapamil can attenuate acute liver injury by down-regulating the production of TNF-?,IL-6 and up-regulating IL-10 in the liver in a dose-dependent manner,possibly via inhibition of NF-?B.

Neuroprotective effect of calcitriol in systemic inflammation induced by lipopolysaccharide / 医学研究生学报

Objective:To investigate neuroprotection of calcitriol in LPS-induced rat systemic inflammation and underlying mechanism. Methods:Adult male Sprague-Dawley rats were randomized into three groups: blank group(6 rats),calcitriol group [23 rats,4?g/(kg?d)?14d] and control group [23 rats,fat milk,4ml/(kg?d)?14d].46 rats were induced systemic inflammation by intraperitoneal injection of LPS(10mg/kg) on day 14th,1 hour after the administration.On post-injection 3,6,9 hour,36 rats were anesthetized to death and obtained rat brain tissue to detect activity of NF-?B by EMSA and to assess TNF-?,IL-10 concentration by ELISA.HE staining was used to determine brain injury. Results:LPS effectively activated NF-?B,enhanced TNF-? expression,induced sporadic neurons damage in brain in the control group and in time-dependent,compared with blank group rats.Calcitriol significantly down-regulated NF-?B activity,TNF-? expression but enhanced IL-10 expression at all time point evaluated,compared with the control group rats. Conclusion:Intraperitoneal injection of LPS can induce brain damage,Calcitriol modulate the inflammatory-antiinflammatory cytokine balance by downregulating activation of NF-?B,reducing over express of TNF-? and elevating IL-10 concentration.

Effect of Flt-3 ligand on fusion vaccine of dendritic cells and induction of antitumor immunity in vitro / 医学研究生学报

Objective:To investigate the effect of flt-3 ligand on the preparation of the fusional vaccine with dendritic cells and colorectal cancer cells,and the anti-tumor immunological reaction of the vaccine. Methods: ①In the presence of Flt-3 ligand、GM-CSF、IL-4 and TNF,the maturation of dendritic cells was made from peripheral blood;The preparation of the fusional vaccine was made in the presence of PEG. ②The biological characteristics of fusion cells,including their morphological specialties, the expression of cell surface phenotypes, their growth curves, inducing specific cytotoxic T lymphocyte(CTL), their possibility to proliferate into a new carcinoma in nude mice etc, were tested to verify their safety when used as anti-tumor immune reactions. Results: ①Flt-3 ligand can stimulate the full maturation of dendritic cells. Dendritic cells and Lovo cells could be fused by PEG. ②The fusion cells exhibited typical biological characteristics. They could not proliferate into new carcinomas in nude mice, and can inhibit the proliferation of Lovo cells efficiently. Conclusion: Flt-3 ligand can enhance the maturation of dendritic cell. The fused cells had poor proliferation abilities and could not proliferate into new carcinomas in immunodeficient animals. The fusion vaccine could induce specific cytotoxic T lymphocytes in vitro and was safe as a vaccine.

Preoperative intra-arterial infusion chemotherapy and chemiluminescence of peripheral blood lymphocyte in patients with gastric cancer / 医学研究生学报

Objective: To study the influence of preoperative arterial infusion chemotherapy on chemiluminescence(CL) of peripheral blood lymphocyte(Ly) in patients with gastric cancer. Methods: 70 patients with gastric cancer were chosen. Peripheral blood samples were gathered to separate lymphocytes at pre-chemotherapy, 1, 3, 5 and 7 days post-chemotherapy respectively. CL and kinetics of lymphocytes were detected. Results:Ly-CL of gastric cancer patients rapidly decreased at 24 hours post-chemotherapy(P 0.05). At same time proliferation index of lymphocytes changed synchronically and correlated positively to Ly-CL (r=0.61,P

p38 MAPK signalling cascades and inflammatory disease / 医学研究生学报

Inflammatory mediators releasing during acute and chronic diseases can activate multiple intracellular signals inducing cascades of the mitogen-activated protein kinase(MAPK) signalling transduction pathway. MAPK plays a significant role in the recruitment of leukocytes to the inflammation sites. Stimulation of leukocytes by pro-inflammatory cytokines is known to activate the MAPK isoform p38. However, the consequences of p38MAPK activation during leukocyte recruitment, adhesion, migration, functions of effector(oxidative burst), and the network of cytokines mediated by p38MAPK are all investigated for further elucidation. Specific p38 inhibitors in reducing the production of inflammatory mediators and providing more effective treatment are now being developed.

The changes of the semen quality and the sperm in patients before and after renal transplantation under scanning electron microscopy / 中华器官移植杂志

Objective To study the changes of the semen quality and the spermatogoa ultrastructure in uremic patients before and after renal transplantation. Methods The semen was analyzed and spermatogoa were investigated under scanning electron microscopy (SEM) in 8 patients before and after renal transplantation and 5 normal volunteers. Results In uremic patients, there was significant decreases in sperm motility, survival rate and sperm density. Under SEM, the deletion of the acrosome, distinct vacuoligation in the nucleus, deficiency of the postacromal and postnuclear ring and ~absence of the middle segment of mitochondrial sheath were found. After renal transplantation, the semen main parameters were significantly improved (P

1,25-Dihydroxyvitamin D_3 and its analogs exert immunoregulatory activitives / 医学研究生学报

The active form of vitamin D,1,25-Dihydroxyvitamin D3 \,is a secosteroid hormone that binds to the vitamin D receptor(VDR),a member of the superfamily of nuclear receptors for steroid hormones,thyroid hormone,and retinoic acid.1,25-Dihydroxyvitamin D3 and its analogue regulate calcium and bone metabolism,control cell proliferation and differentiation,and exert immunoregulatory activities.Recent advances in understanding their functions and novel insights into the immunomodulatory mechanisms they control suggest a wider applicability in the treatment of autoimmune diseases and induction of allograft tolerance.In addition to direct effects on T cell activation,1,25-Dihydroxyvitamin D3 and its analogue modulate with different mechanisms the phenotype and function of antigen-presenting cells(APC),and,in particular,of dendritic cells(DC).In vitro and in vivo experiments have shown that 1,25-Dihydroxyvitamin D3 and its analogue induce DC to acquire tolerogenic properties that favor the induction of regulatory rather than effector T cells.These intriguing actions of 1,25-Dihydroxyvitamin D3 and its nanlogue have been demonstrated in several experimental models and could be exploited,in principle,to treat a variety of human autoimmune diseases,or inhibit allograft rejection.

A histopathological comparison of changes after neo-adjuvant radiotherapy in rectal cancer / 医学研究生学报

Objective: To compare the histopathological changes after neo-adjuvant radiotherapy and to elucidate the mechanism of radiotherapy in rectal cancer. Methods: 80 patients with rectal cancer in pTNM stage Ⅱ or Ⅲ were enrolled between April 2000 and December 2002.They were randomly assigned to surgery alone or preoperative neo-adjuvant radiotherapy.The conventional radiotherapy scheme was followed: 40 Gy in 2.0 Gy fractions.The treatment last 4 weeks and it is usually followed by an interval of 1-2 weeks before the operation.Pathological changes including necrosis of tumor and changes of matrix and vessels were graded. Results: Significant tumor regression(RCRG 1) was seen in 14 cases(35 percent) after radiotherapy,while partially tumor regression(RCRG 2) was seen in 18 cases(45 percent).Significant necrosis was observed in 72.5 percent of cases after preoperative radiotherapy,most foci of adenocarcinoma were replaced by fibrosis in 80 percent of cases,and intimal thickening in most of the vessels were seen in 77.5 percent of cases.The frequency of these pathological changes after radiotherapy was significantly more than control group. Conclusion: Necrosis,fibrosis and thickening of vascular intima in the rectal cancer tissue after radiotherapy is more frequent than those without radiotherapy.It may be the potential reason for increased resection rate and sphincter-saving after radiotherapy.

Immunomodulative effects of 1,25-Dihydroxyvitamin D_3 on the predominant Th1 response rat / 解放军医学杂志

Objective To study the immunomodulative effects of 1,25-Dihydroxyvitamin D_3 1,25-(OH)_2D_3 on the predominant Th1 response rats. Methods Lewis rats had been fed with 1,25-(OH)_2D_3 (1000ng per rat) for 14 days. The rats in control group were administered vehicle with the same volume as the drug to serve as the experimental group, and then LPS (10ng/kg) was administered intraperitoneally in both groups on the 15th day. 15 rats of each group were sacrificed 6h later and immunological index was measured. Mortality of the remaining ten rats in both group have been observed. Results There was no death in experimental group, while five control rats died at 24h (5/10, 50%), and all the other five control rats survived at 96h. IL-12 and IFN-? were decreased significantly in the experiment group compared with control (3986?328pg/ml vs 4160?289pg/ml, P=0.028; 4840?802pg/ml vs 5264?524pg/ml, P=0.020), while IL-4 was increased (5.57?1.75pg/ml vs 3.72?1.62pg/ml, P=0.036). In white pulp of the spleen of experimental rat the number of lymphocytes decreased significantly as shown with HE-staining, and the PCNA positive cells were distributed focally or dispersively. In addition, by using flow cytometer, it was found that CD4~+ CD25~+ positive lymphocytes were increased significantly in the spleen of experimental rats (1.09%?0.29% vs 0.73%?0.00%, P

Effect of human growth hormone on cell cycle kinetics in colonic cancer cells / 肠外与肠内营养

Objectives:The effects of human growth hormone (hGH) on cell cycle kinetics were studied in human colonic cancer cell line, LS-174-T cell.　Methods: The cells were cultured in RPMI－1640 medium for 24 hours with hGH at concerntration of 50, 100, 200 ng/ml with or without cisplatin. Cell cycle kinetics was analyzed by flow cytometry.　Results: The significant effects of hGH on cell cycle kinetics were found in the cell line. Percentage of S phase increase (P<0.01) and percentage of G2/M phase decreased (P<0.01).DNA Index (DI) didn't increase.The cells had a lot of apoptosis and percentage of S phase decreased (P<0.01) with addition of cisplatin.　Conclusions: In vitro hGH may induce the proliferation of colonic cancer cells. Cisplatin may suppress the stimulatory effects of hGH on S phase and increase the apoptosis of colonic cancer cells.

An improved method for isolation of mouse islets and islet transplantation / 中华器官移植杂志

Objectives　To study of the method for isolation and transplantation of mouse islets. Methods　The method for isolation of mouse islets described by Gotoh G was modified. The solution of digestion was injected not through the common bile duct but through gallbladder. Soybean trypsin inhibitor and BSA were added into the digestive and Ficoll separation solutions. Results　The yield of islets was increased from 41.7±13.2 to 266.5±32.1(P<0.01). Islet viability was more than 95!%. Among the purified islets, there was no exocrine tissue but few ductal fragments. Conclusions　By the improved method, digestive solution could be injected into pancreas without inverted microscope, which made manipulation easier and more successful. Having avoided the digestive effect of trypsin on islets, the yield of islets was increased and good repetitiousness was obtained.

Posttraumatic expression of MHC II molecules: an experimental and clinical study / 中华创伤杂志(英文版)

OBJECTIVE: To evaluate the role of MHC II expression in posttrauma immune disturbances and infections. METHODS: In experimental study, peritoneal macrophages were harvested from traumatized mice and treated with GM-CSF, Ia molecules were determined by flow cytometry. In 24 trauma patients, monocyte HLA-DR expression was measured by APAAP technique. RESULTS: Marked inhibition of MHC II molecule expression was found in both traumatized mice and patients. In traumatic patients with infection, the inhibition was more severe. Treatment with GM-CSF in mice partially restored the Ia expression. CONCLUSIONS: Inhibition of MHC II molecules plays an important role in postrauma immune disturbances. There is a close relationship between HLA-DR inhibition and clinical infections.

Hepatoid adenocarcinoma of the stomach: report of 3 cases and review of the literature in recent ten years / 中国癌症杂志

Purpose:To analyze the clinical manifestations, so the diagnosis of hepatoid adenocarcinoma of the stomach (HAS) may be made and treatment instituted as early as possible. Methods:A total of 65 cases of HAS reported in the literature in recent ten years reviewed.Results:①Clinical symptoms and signs: The incidence of HAS in male was higher than that in female (6.2:1).Upper abdominal discomfort and physical signs of mass bclow the sternum were most commonly seen.②Diagnosis: The serum content of AFP were discombfort high level with a positive rate of 66.7%(22/33). The positive rate of AFP expression with immunohistochemical method was 94.5%(52/55).The percentage of liver metastasis detected by US B or CT was 20.5%(9/44) preoperation, and mostly seen at the gastric sinus was ahout 63.3%(19/30). The final diagnosis of HAS depends on gastrocopy and pathology. ③Treatment and Prognosis: The possibility of radical operation(D 2 ) is only 17.9%(5/28). The death ratio within one year was 56.3%(18/32).Conclusions: HAS is primarily a gastric carcinoma. The serum AFP levels are help fulin the diagnosis and differential diagnosis of HAS. The diagnostic evidence of HAS is dependant on its specific forms. The prognosis is often poor because of frequent liver metastasis.

Immunomodulatory effects of 1,25-dihydroxyvitamin D3 / 肠外与肠内营养

1,25-dihydroxyvitamin D3,the activated form of vitamin D, is a secosteroid hormone.In addition to its central function in calcium and bone metabolism,1,25-dihydroxyvitamin D3 has important effects on the growth and differentiation of immune system.1,25-dihydroxyvitamin D3 interacts with its specific receptor,the vitamin D3 receptor(VDR).APCs and T cells can be direct targets of the hormone,leading to the inhibition of pathogenic effector T cells and enhancing the frequency of T cells with regulatory properties, largely via induction of tolerogenic DCs.1,25-dihydroxyvitamin D3 and its analogs have been shown to inhibit autoimmune diseases and graft rejection in several experimental models.It is a complicated and fertile area of investigation. By the investigation may important new therapies emerge for autoimmune disease and graft rejection.

Effect of vitamin E on the chronic graft rejection / 肠外与肠内营养

At present, the immunological tolerance in transplantation induced by multi-mechanisms, to inhibit the chronic graft rejection, represents an important trend in the field of transplantation. This review summarizes the new researches about immune and non-immune factors in this field. At the same time, this review also discusses that the high-dose vitamin E, through changing the ratio of Th/Ts in vivo and not improving the level of specific-antibody, regulates the immune system. In addition, the potent antioxidation of vitamin E has advantage to release the oxidate press of tissue and the damage of blood vessels. In the end, the reporter prospects the signification of vitamin E to inhibit the chronic graft rejection and points out the potential questions.