Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma

AIM: To explore the correlation between expression of somatostatin (SS), gastrin (GAS) and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma.METHODS: Sixty-two large intestine cancer tissue samples were randomly and retrospectively selected from patients with large intestine carcinoma. Immunohistochemical staining for bcl-2, bax, GAS, SS was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.According to the semi-quantitative integral evaluation, SS and GAS were divided into three groups as follows. Scores1-3 were defined as the low expression group, 4-8 as the intermediate expression group, 9-16 as the high expression group. Bax and bcl-2 protein expressions in different GAS and SS expression groups of large intestine carcinoma were assessed.RESULTS: The positive expression rate of bax had a prominent difference between SS and GAS high, intermediate and low expression groups (P＜0.05, x2ss = 9.246; P＜0.05,x2GAS = 6.981). The positive expression rate of bax in SS high (80.0%, 8/10) and intermediate (76.5%, 13/17)expression groups was higher than that in low expression group (40.0%, 14/35) (P＜0.05, x2high vs low = 5.242; P＜0.05,x2middle vs low = 6.097). The positive expression rate of bax in GAS high expression group (27.3%, 3/8) was lower than that in low expression group (69.4%, 25/36) (P＜0.05,x2 = 4.594). However, bax expression in GAS intermediate expression group (46.7%, 7/15) was lower than that in low expression group, but not statistically significant. The positive expression rate of bcl-2 had a prominent difference between SS and GAS high, intermediate and low expression groups (P＜0.05, x2ss = 7.178; P＜0.05, x2GAS = 13.831). The positive expression rate of bcl-2 in GAS high (90.9%, 10/11)and intermediate (86.7%, 13/15) expression groups was higher than that in low expression group (44.4%, 16/36)(P＜0.05,x2high vs low = 5.600; P＜0.05, x2 middle vs low = 7.695).However, the positive expression rate of bcl-2 in SS high (40.0%, 4/10) and intermediate (47.1%, 8/9) expression groups was lower than that in low expression group (77.1%, 27/35)(P＜0.05, x2 high vs low = 4.710; P＜0.05, x2 middle vs low = 4.706).There was a significant positive correlation between the integral ratio of GAS to SS and the integral of bcl-2 (P＜0.01,r=0.340). However, there was a negative correlation between the integral ratio of GAS to the SS and bax the integral of (P＜0.05, r = -0.299).CONCLUSION: The regulation and control of gastrin,somatostatin in cell apoptosis of large intestine carcinoma may be directly related to the abnormal expression of bcl-2, bax.

The Effect of GHRH, GHRP-2 and Somatostatin on GH Secretion by fetal pituitary

Growth hormone releasing peptide (GHRP-2) is a synthetic hexapep-tide which specifically stimulates secretion of growth hormone (GH) by fetal pitu-itary somatotrophs through a new membrane receptor, which is different from growth hormone releasing hormone (GHRH) and somatostatin (SMS) receptors.We used cell cultures of human fetal pituitary somatotroph cells to investigate the effect of GHRH, GHRP-2 and somatostatin on GH secretion. The results showed that the mechanism of GHRH/SMS and GHRP-2 was different- This indicated that a different intracellular signal transduction system might also play a crucial role in the regulation of GH secretion.

Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts

AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.

Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages

BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

AIM:To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).METHODS:120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays,respectively,and examined for HER2 overexpression and gene amplification by IHC and CISH.RESULTS:Twenty-four tumors (20%) expressed HER2 immunohistochemically.An IHC score of ≥ 2+ was observed in 20 tumors (16.6%).HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases.A high concordancerate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH),since 19 of the 20 IHC positive cases were amplified (95%).All amplified cases had 2+ or 3+ IHC results.Amplification was associated with intestinal phenotype (P < 0.05).No association with grading,staging or survival was found.CONCLUSION:In gastric cancer,HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.

High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis

AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.

Somatostatin receptor subtype 2-mediated scintigraphy and localization using ^(99m)Tc-HYNIC-Tyr^3-octreotide in human hepatocellular carcinoma-bearing nude mice

AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma. METHODS: The expression of somatostatin receptor 2 (SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTc uptake between tumor tissue and vital organs. RESULTS: We demonstrated the expression of SSTR2 mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue, liver and kidney of the tumor-bearing mice. CONCLUSION: Based on expression of the SSTR2 mRNA in human HCC, 99mTc-HYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionudide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclide-labeled somatostatin analog for HCC are of great value to be further studied.

Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People

Objective To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 （PPARγ2） promoter and coronary heart disease （CHD）. Methods This case-controlled study was conducted in nondiabetic Chinese Han people, which enrolled 455 patients with CHD （cases） and 693 subjects without CHD （controls）. Data of clinical indexes were collected, including height, body weight, waist circumstance, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, smoking, drinking, physical activity, as well as body mass index （BMI）. Fasting blood glucose （FBG）, plasma total cholesterol （TC） and triglyceride （TG） levels were measured. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T, allelic frequency, clinical indexes, and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model. Results The genotype frequencies of CC, CT and TT in PPARγ2 promoter C-689T were 89.7%, 9.9% and 0.4% in the case group, and 93.1%, 6.6% and 0.3% in the control group, respectively （CC vs. CT＋TT, χ^2= 6.243, P=0.041）. Carriers of -689T allele （n=95） had significantly higher TC level than non-carriers （n=1053） （5.12±1.26 vs. 4.76±1.22 mmol/L, P=0.001）. Male carriers of -689T allele （n=51） were significantly higher in waist circumference, body weight, TC and TG than male non-carriers （n=656） （all P〈0.05）. In subjects whose BMI was over 25 kg/m2, carriers of -689T allele （n=82） had significantly higher levels of waist circumference, BMI, SBP and TC than non-carriers （n=231） （all p〈0.05）. The -689T allele was an independent risk factor for CHD （OR=1.668, 95%CI： 1.031-2.705, P=0.037） after adjusting for age, gender, waist circumference, body weight, BMI, smoking, physical activities, SBP, DBP, FBG, TC and TG level. Conclusion These data support the hypothesis that the -689T allele is associated with an increased risk of CHD, in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.

Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.

Loss of human epidermal receptor-2 in human epidermal receptor-2+breast cancer after neoadjuvant treatment:A case report

BACKGROUND Human epidermal receptor-2(HER-2)expression has been reported to be discordant between primary tumor and metastatic tissue.CASE SUMMARY We presented a case diagnosed with the HER-2+breast cancer patient who exhibited changes in the expression of HER-2 receptors on tumour samples from surgical specimens obtained after neoadjuvant treatment(NAT)compared with initial biopsy.The patient underwent a HER-2-targeted therapy consequently,in spite of HER+gene loss.After the surgery,the patient subsequently underwent endocrine therapy and radiotherapy.CONCLUSION Changes in HER-2 expression after NAT should be retested by physicians and pathologists before systemic treatment instead of avoiding further HER-2-targeted therapy,and we will perform immunohistochemical multiple-spot biopsy analyses of other important clinical issues to better define prognosis and tailor subsequent adjuvant therapy.

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

Role of Protease Activated Receptor-2 Expression in Renal Interstitial Fibrosis Model in Mice

Summary： The role of protease activated receptor-2 （PAR-2） in the renal tubulointerstitial lesion induced by unilateral ureteral obstruction （UUO） was explored. Mice were sacrificed on the day 1, 3, 5, 7, 10, 14 and 21 after UUO. The expression of PAR-2 mRNA and protein and a-smooth muscle actin （α-SMA） protein in tubuloin,terstitium was detected by RT-PCR and immunohistochemistry at each time point, respedtively. The results showed that the PAR-2 expression in renal tubulointerstitium was increased progressively starting from 24 h to the day 14 post-ligation, and it was significantly associated with the relative volume of interstitium and the positive area of α-SMA. PAR-2 was mainly expressed in renal tubule epithelial cells, especially in proximal tubular cells. It also located in renal capillary ansa, interstitial infiltrate cells and fibroblasts. It was concluded that PAR-2 was active in interstitial and tubular cells in the early phase of fibrotic process and played an important role in mediating the tubulointerstitial lesion after UUO.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Peroxisome Proliferator-activated Receptor-γ2 Pro12Ala and C-689T Polymorphisms and Haplotypes Affect the Profiles of Coronary Heart Disease in Diabetic Chinese People

Objectives Peroxisome proliferator-activated receptor-γ2（PPARγ2） variant Pro12Ala was demonstrated with risk of coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Another variant C-689T in the promoter was reported with lower receptor activity but lack of reports on association between C-689T and CHD or T2DM. Methods A total of 351 subjects without CHD and T2DM （controls） and 125 patients with CHD and T2DM （cases） were enrolled in our case-control study. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to detect Pro12Ala and C-689T polymorphisms. And effects on CHD merged with T2DM of the two polymorphisms were analyzed in individual and haplotype analyses. Results In the study, Pro12Pro, Pro12Ala and Ala12Ala genotype frequencies were 92.9%, 6.8% and 0.3% in controls; 92.8%, 7.2% and 0.0% in cases respectively whilst CC, CT and TT genotype frequencies were 93.4%, 6.3% and 0.3% in controls; 92.8%, 7.2% and 0.0% in cases respectively. Pro12Ala and C-689T polymorphisms were in strong linkage disequilibrium （D＇=0.81, P=0.000） and the observed haplotype frequency of Pro-C, Pro-T, Ala-C and Ala-T was 0.957, 0.006, 0.008 and 0.028 respectively. No significant associations were detected between the two polymorphisms and CHD merged with T2DM in either individual or haplotype analyses. In subjects with obesity [body mass index （BMI）≥25 kg/m^2], we found that both Pro12Ala and C-689T polymorphisms were associated with BMI. In haplotype analyses, we found that Pro12Ala and C-689T haplotypes had associations with systolic blood pressure in total population, with BMI, waist circle and total cholesterol（TC） in obesity subgroup and with fasting blood glucose and TC in males. Conclusions PPARγ2 Pro12Ala and C-689T polymorphisms and haplotypes affect the profiles of CHD merged with T2DM in Chinese Han people.

肺癌胸腔镜根治术标本TCF21、ANGPT1、SSTR2表达及联合检测预测术后复发转移模型构建与验证

目的探讨肺癌胸腔镜根治术标本中肿瘤转移相关基因转录因子21(TCF21)、血管生成素1(ANGPT1)、生长抑素受体2(SSTR2)表达情况,构建术后复发转移的联合预测模型并进行验证,为临床早期预测术后复发转移提供参考。方法前瞻性选取2020年3月—2022年2月于本院行胸腔镜根治术的149例肺癌患者为研究对象,根据术后1年是否发生复发转移分为复发转移组(n=32)、未复发转移组(n=117)。采用随机森林算法对术后复发转移的特征变量进行筛选与降维。Logistic回归分析术后复发转移的相关影响因素、拟合多个变量联合预测术后复发转移的模型。采用受试者工作特征曲线(ROC)分析各原始协变量及联合预测因子New对术后复发转移的预测价值。结果复发转移组T分期、N分期高于未复发转移组,清扫淋巴结站数、清扫淋巴结N2站数、清扫淋巴结数目及TCF21、ANGPT1、SSTR2表达量低于未复发转移组(P<0.05);随机森林算法显示重要性排序前3的变量分别是TCF21、SSTR2、ANGPT1表达量;Logistic回归分析显示TCF21、SSTR2、ANGPT1表达量为术后复发转移的相关影响因素(P<0.05);联合预测因子New预测术后复发转移的曲线下面积(AUC)大于各原始协变量(P<0.05);个体值预测显示在诊断准确率为95.97%的条件下,该患者不会发生复发转移,且经联合预测因子New验证证实该病例未发生复发转移。结论肺癌胸腔镜根治术术后复发转移患者中TCF21、ANGPT1、SSTR2表达量降低,Logistic回归模型拟合TCF21、ANGPT1、SSTR2生成的联合预测因子对术后复发转移具有一定预测价值。

早期2型糖尿病患者血浆生长抑素、胰高血糖素样肽1和胰升糖素水平的变化

目的观察早期2型糖尿病患者血浆生长抑素、胰高血糖素样肽1(GLP-1)和胰升糖素的动态变化。方法以早期糖尿病患者(糖尿病组,n=49)和健康对照者(对照组,n=21)作为研究对象。采用口服葡萄糖耐量试验(OGTT),分别于空腹和糖负荷后2 h,测定血浆生长抑素、GLP-1和胰升糖素水平,计算上升率并分析相关性。结果糖尿病组空腹和糖负荷后2 h的血浆生长抑素和GLP-1水平及空腹胰升糖素水平均显著低于对照组(P<0.05),且两组糖负荷后2 h的测定值均高于空腹值;糖尿病组血浆胰升糖素水平和生长抑素的上升率显著高于对照组(P<0.05),两组间血浆GLP-1水平的上升率比较差异无统计学意义(P>0.05)。糖尿病组血浆生长抑素水平的上升率与血浆GLP-1水平的上升率呈正相关(r=0.367,P=0.015)。结论生长抑素对GLP-1抑制减少可能是早期2型糖尿病患者的一种代偿反应;在2型糖尿病早期胰升糖素已有不适当的分泌增多,相比GLP-1,血糖和胰岛素在其中的作用更为重要。

金芪降糖片改善2型糖尿病胰岛素抵抗的研究

目的:探讨金芪降糖片改善2型糖尿病胰岛素抵抗及胰高血糖素、生长抑素治疗前后变化。方法:2型糖尿病(T2DM)患者100例,辨证分为阴虚热盛、湿热困脾、气阴两虚和阴阳两虚4型,使用金芪降糖片,疗程3个月,治疗前后测定空腹血糖(FBG)、空腹胰岛素(FINS)、胰高血糖(Gluc)、生长抑素(SS),并计算胰岛素敏感性(IAI)、胰岛素抵抗指数(HOMA-IR)。结果:金芪降糖片能降低T2DM阴虚热盛型、湿热困脾型、气阴两虚型患者的Gluc及升高SS,从而增加IAI,降低HOMA-IR,达到降低血糖。结论:金芪降糖片通过升高SS、降低Gluc,改善2型糖尿病阴虚热盛型、湿热困脾型、气阴两虚型患者的胰岛素抵抗。

模拟失重大鼠胃窦肌层Cox-2表达和血清SS及VIP水平的变化

目的 研究尾悬吊模拟失重对大鼠胃窦肌层诱生型环氧化酶2（Cox-2）表达和血清生长抑素（SS）、血管活性肠肽（VIP）水平的影响。方法 健康雄性Wistar大鼠64只，随机分为8组，按模拟失重时相分为0h（对照组）和6h、12h、1d、2d、3d、5d、7d组（n=8）。采用尾悬吊法建立模拟失重动物模型。应用RT-PCR、Western blotting和免疫组化技术检测各组大鼠胃窦肌层组织中Cox-2 mRNA和蛋白表达情况，应用放免法测定血清SS、VIP浓度。结果 免疫组化结果显示，Cox-2蛋白阳性表达为棕褐色，悬吊6h、12h、1d大鼠胃窦平滑肌细胞胞质染色变深并出现部分核染色阳性，2d开始逐渐恢复，但胞质着色仍较对照组深。RT-PCR结果显示，Cox-2 mRNA表达水平在尾悬吊6h即出现显著增高，12h、1d时仍呈高水平表达（P＜0.05），2d后表达水平逐渐回落（P＞0.05）。Western blotting结果显示，悬吊6h大鼠胃窦肌层Cox-2蛋白表达水平显著升高，12h、1d持续高表达，与对照组比较差异有统计学意义（P＜0.05），2d后逐渐恢复正常水平（P＞0.05）。血清SS浓度在尾悬吊模拟失重2-3d达峰值，与对照组比较差异有统计学意义（P＜0.05），其他各时相浓度值波动明显。血清VIP浓度同样在模拟失重早期即显著升高（P＜0.05），峰值出现在6-12h，其后经过2-3d的回落后复又升高。结论 胃窦肌层Cox-2表达异常和血清SS及VIP水平变化在胃窦失重应激性动力障碍及恢复过程中可能发挥重要作用。

生长抑素与大肠癌细胞凋亡及调控基因bcl-2、bax及p53关系的研究

目的 探讨生长抑素 (SS)与大肠癌细胞凋亡指数 (AI)和凋亡调控基因p5 3、bcl 2、bax的关系。方法 采用免疫组织化学SABC法和分子生物学细胞原位凋亡检测技术中的TUNEL法 ,检测 6 2例大肠癌组织中SS、p5 3、bcl 2、bax及细胞凋亡的表达情况。结果 在大肠癌组织SS高表达组、中表达组的AI明显高于SS低表达组 (P <0 .0 1) ;p5 3、bcl 2、bax阳性表达率在SS低表达组、中表达组、高表达组三组间相比较存在着明显差别 (P <0 .0 5 ) ,其中bax在SS高表达组、中表达组的阳性表达率明显高于低表达组 (P <0 .0 5 ) ;bcl 2与其相反。p5 3在SS高表达组的阳性表达率明显低于低表达组 (P <0 .0 5 ) ;而p5 3在SS中表达组表达的阳性表达率低于低表达组 ,但其统计无明显差别 (P >0 .0 5 )。结论 生长抑素对大肠癌细胞凋亡的调控可能与 p5 3、bcl 2。