[Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment].

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Network meta-analysis of the intervention effects of different exercise measures on Sarcopenia in cancer patients.

PURPOSE: This study aims to investigate the impact of four exercise modes (aerobic exercise, resistance exercise, aerobic combined with resistance multimodal exercise, and stretching) on the physical performance of cancer patients. METHODS: Randomized controlled trials (RCTs) were exclusively collected from PubMed, EMBASE, Web of Science, and The Cochrane Library, with a search deadline of April 30, 2023. Different exercise interventions on the physical performance of cancer patients were studied, and the Cochrane risk of bias assessment tool was employed to evaluate the quality of the included literature. Data analysis was conducted using STATA 15.1 software. RESULTS: This study included ten randomized controlled trials with a combined sample size of 503 participants. Network meta-analysis results revealed that aerobic combined with resistance multimodal exercise could reduce fat mass in cancer patients (SUCRA: 92.3%). Resistance exercise could improve lean mass in cancer patients (SUCRA: 95.7%). Furthermore, resistance exercise could enhance leg extension functionality in cancer patients with sarcopenia (SUCRA: 83.0%). CONCLUSION: This study suggests that resistance exercise may be more beneficial for cancer-related sarcopenia.In clinical practice, exercise interventions should be tailored to the individual patients' circumstances. REGISTRATION NUMBER: This review was registered on INPLASY2023110025; DOI number is https://doi.org/10.37766/inplasy2023.11.0025 .

Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

OBJECTIVE: Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. MATERIALS AND METHODS: A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. RESULTS: The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1ß risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1ß, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. CONCLUSIONS: A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1ß, IL-6, and IL-17.

[Analysis of effective connectivity in default mode network in male long-term smokers based on dynamic causal modeling].

Objective: To investigate the alterations in effective connection of default mode network (DMN) in long-term male smokers and its correlation with clinical characteristics of smoking. Methods: A total of 131 subjects through WeChat platform and underwent resting-state functional magnetic resonance (rs-fMRI) examinations were recruited, including 76 long-term smokers [long-term smoking group, male, aged 20 to 55 (32.1±6.3) years] and 55 non-smokers [healthy controls, male, aged 20 to 55(32.3±7.4) years] from January 2014 to December 2018. Long-term smokers were defined as those who smoked at least 10 cigarettes per day for more than 2 years, and met the Diagnostic and Statistical Manual of Mental Disorders-Four Edition (DSM-Ⅳ) criteria for substance dependence. Four major nodes of DMN, including left inferior parietal lobule (LIPL), right inferior parietal lobule (RIPL), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) were chosen as for the region of interest. The effective connectivity (EC) alterations of DMN between smoking group and healthy controls were compared using dynamic causal modeling (DCM). The correlation between EC with significant difference among the two groups and Nicotine Dependence Scale (FTND) score, pack-year score and smoking duration were evaluated. Results: Compared to the healthy controls, the EC of LIPL to PCC and PCC to mPFC were decreased in the smoking group (EC = -0.091, -0.174, respectively, Bayesian-PP>0.95), and the EC of RIPL to PCC was increased (EC = 0.136, Bayesian-PP>0.95). Besides, EC of LIPL to PCC showed negative correlation with pack-year scores(r=-0.282,P=0.017). No significant linear correlations were observed between EC with significant group difference and FTND score or smoking duration (r=-0.103、-0.089,all P>0.05). Conclusion: Long-term smokers showed multiple abnormalities in IPL-PCC-mPFC circuits, and associated with the pack-year scores.

[Clinical features and prognosis of patients with leptomeningeal metastases].

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95%CI:2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival (P<0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

[Predictive value of platelet aggregation rate in hemodynamically significant patent ductus arteriosus in preterm infants].

Objective: To explore the predictive value of platelet aggregation rate in patent ductus arteriosus in preterm infants. Methods: This prospective nested case-control study enrolled 72 preterm infants with gestational age<32 weeks, who were admitted to Neonatal Intensive Care Unit of Xuzhou Central Hospital from August 2017 to October 2019. The echocardiography was performed on the 4th to 5th day after birth, and the preterm infants who met the diagnostic criteria of hemodynamically significant patent ductus arteriosus (hsPDA) were included into hsPDA group, and the control group was comprised of matched preterm infants with non-hsPDA according to the proportion of 1∶2. The basic characteristics of the preterm infants were recorded, and their complete blood counts and platelet aggregation function were examined. Clinical data were compared by student's t test and chi-square test between the two groups. The risk factors and their predictive values were analyzed by binary logistic regression analysis and receiver operating characteristic curve. Results: There were 24 preterm infants (16 boys) in the hsPDA group, and 48 (30 boys) in the control group. The incidence of neonatal respiratory distress syndrome (NRDS) grade II-IV in the hsPDA group was higher than that in the control group (67% (16/24) vs. 27% (13/48), χ²=10.422, P=0.001). The thrombocytocrit and adenosine diphosphate-induced platelet aggregation rate in the hsPDA group were lower than those in the control group (0.002 1±0.000 9 vs. 0.002 8±0.000 9, 0.21±0.10 vs. 0.32±0.07, t=-3.043 and -5.093, P=0.004 and <0.01, respectively); while the platelet volume in the hsPDA group was greater than that in the control group ((10.3±2.4) vs. (9.2±2.0) fl, t = 2.713, P = 0.033). The other platelet parameters (platelet count, platelet distribution width, and large platelet ratio) and platelet aggregation rate induced by other inducers (collagen, epinephrine and arachidonic acid) were not significantly different between the two groups (all P>0.05). The low platelet aggregation rate induced by adenosine diphosphate and low thrombocytocrit were independent risk factors for hsPDA in preterm infants (OR=4.525 and 3.994, 95%CI: 1.305-15.689 and 1.143-13.958, respectively). And the adenosine diphosphate-induced platelet aggregation rate had moderate predictive value for hsPDA in preterm infants, as the area under the receiver operating characteristic curve was 0.809, and the cutoff value was 0.245 with 0.67 sensitivity and 0.86 specificity. Conclusions: Poor platelet aggregation function and low thrombocytocrit are independent risk factors for hsPDA in preterm infants with gestational age<32 weeks. Low platelet aggregation rate induced by adenosine diphosphate has moderate predictive value for hsPDA patency.

[Involvement of Src kinase in the down-regulation of ultra-rapid delayed rectifier K(+)current induced by tumor necrosis factor-α in cardiomyocytes].

Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 µmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.

BACKGROUND: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.

[Clinical analysis of 9 cases with Anti-leucine-rich glioma inactivated 1 protein antibody associated limbic encephalitis].

Objective: This study was to describe the clinical characteristics of Anti-leucine-rich glioma inactivated 1 protein(LGI1) antibody associated limbic encephalitis. Methods: Clinical data including clinical features, laboratory and radiological findings, treatment and prognosis of the 9 patients were analyzed. Results: In all 9 cases, 6 cases experienced epileptic seizure, 5 cases had psychosis, 7 cases presented with memory impairment, 4 cases showed faciobrachial dystonic seizure, 2 had refractory hyponatremia. One case presented with typically acute Guillain-Barre syndrome (GBS). Anti-LGI1 antibody was detected in 6 cases in cerebrospinal fluid (CSF) samples and 9 in serum samples. Seven cases out of 9 had brain imaging abnormalities. All 9 cases found no evidence of tumors. Eight cases were given immune therapy. During a 1-16 months follow-up, 1 case had complete recovery, 5cases had various degree of sequelae , among whom 4 had memory disturbance and 1 case had changed personality. 2cases were lost to follow-up. Conclusions: Limbic encephalitis is the most common manifestation of anti-LGI1 antibody associated encephalitis. Faciobrachial dystonic seizure (FBDS) is a specific symptom which favors an early diagnosis. Tumor is uncommon to see. The disease has a relatively favorable prognosis while impaired memory can be seen as a common sequelae.

Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity

Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway.

Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity.

Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway.

Effect of glycated hemoglobin on heart function of the patients with revascularization of coronary artery.

BACKGROUND: Patients with diabetes after coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) treatment for coronary artery disease (CAD) had higher mortality rates than those without diabetes. There were limited data comparing the cardiac and metabolic differences between diabetes and non-diabetes for CABG and PCI and about impact of pre-procedure GHb level on systolic heart function in patients with diabetes. AIMS: To explore the cardio-metabolic differences and to evaluate their potential as significant risk factors. SUBJECTS AND METHOD: 124 patients with diabetes and 170 patients without diabetes were enrolled. Coronary lesions (≥ 70% stenosis in at least one major coronary artery) were documented by angiography. Patients with diabetes were divided into different groups by GHb, Coronary lesions (≥ 70% stenosis in at least one major coronary artery) were documented by angiography. CABG and PCI were performed for all the patients. Cardio-metabolic risk factors before revascularization were compared between them. RESULTS: Diabetics with GHb ≥ 8% had lower cardiac ejection fraction (EF) values than those with GHb<8% (P<0.05) or patients without diabetes (P<0.05). And count of vascular lesions between the groups was not statistically significant. Observed EF as a dependent variable negatively correlated to GHb levels (P<0.05). The levels of glycated hemoglobin A1c (GHbA1c) rose with increased fasted blood glucose (FBG) values (P<0.001). Even with treatment for hyperglycemia and dyslipidemia, overall levels of fasting blood sugar (FBG, P<0.001), GHbA1c (P<0.001), and triglycerides (TG, P<0.05) in patients with diabetes were still higher than those without diabetes respectively. CONCLUSION: Poorer glucose control with GHb ≥ 8% and decreased systolic heart function are significant risk factors that potentially contribute to worse prognosis for CABG or PCI treatment. Elevated levels of FBG, GHbA1c, and TG are evident for patients with diabetes compared to patients without diabetes prior to revascularization.

Artificial microRNA interference targeting AT(1a) receptors in paraventricular nucleus attenuates hypertension in rats.

Excessive sympathetic activity has a crucial role in the initiation and progression of chronic structural alterations in the heart and vessels associated with hypertension. Angiotensin II type 1a receptors (AT(1a)R) in paraventricular nucleus (PVN) are involved in sympathetic overdrive and hypertension. The present study was designed to investigate the cardiovascular beneficial effects of the AT(1a)R gene silence in the PVN in hypertension. The PVN microinjection of recombinant adenoviral vectors expressing either artificial microRNA (amiRNA) targeting AT(1a) receptors (Ad-miR-AT(1a)) or control microRNA (Ad-miR-Con) were carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. The vectors were labels with green fluorescent protein (GFP). The successful amiRNA interference was confirmed by the AT(1) receptors reduction and the GFP expression in the PVN. Significant depressor effects were observed from day 5 to day 20 after Ad-miR-AT(1a) treatment in SHR. Ad-miR-AT(1a) treatment decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocytes, myocardial fibrosis, media thickness, and the media/lumen ratio of the aorta and the mesenteric artery in SHR. The amiRNA interference reduced the basal sympathetic activity, cardiac sympathetic afferent reflex, plasma norepinephrine and plasma angiotensin II in SHR. These results indicate that amiRNA interference targeting AT(1a)R in the PVN decreases arterial blood pressure, blunts sympathetic activity and improves myocardial and vascular remodeling in SHR.

Expression of IGF-1R in colorectal polyps and its role in colorectal carcinogenesis.

Insulin-like Growth Factor Receptor 1 (IGF-1R) may play a role in the neoplastic progression of colorectal cancer because it is related to both cellular proliferation and differentiation. The aim of this study was to further elucidate the role of IGF-1R in colorectal carcinogenesis by evaluating IGF-1R expression in different types of precancerous colorectal polyps and comparing its expression to normal mucosa and colorectal carcinoma. A total of 47 colorectal polyps and their respective adjacent normal mucosa were collected from 32 patients. In addition, 20 colorectal adenocarcinoma tissues were obtained from patients undergoing colorectal resection, and 12 normal non-malignant colorectal mucosal tissues collected from outpatients served as the control group. The pit patterns of polyps were classified by the Kudo classification scheme through magnifying chromoendoscopy. Immunohistochemistry and quantitative real-time RT-PCR were utilized for expression analysis of IGF-1R in colorectal mucosa, polyps, and adenocarcinoma tissue. The results of immunohistochemistry showed no significant differences in IGF-1R expression in inflammatory polyps compared with their surrounding normal mucosa by the Mann-Whitney U test (p=0.251); however, tubular adenoma and villous adenoma tissues exhibited significantly higher levels of IGF-1R expression (p=0.000). The results of real-time RT-PCR showed that IGF-1R was transcribed at a high level in colorectal adenomatous polyps and adenocarcinoma compared with their respective paired normal mucosa. Spearman's rank correlation two-variable analysis was used to demonstrate a significant correlation between the expression of IGF-1R and neoplastic progression from normal mucosa to adenomatous polyps and finally to colorectal cancer (r=0.574, p=0.000). This study suggests that the expression of IGF-1R correlates with the degree of carcinogenesis. In addition, these results demonstrated that there is a significant correlation between the level of IGF-1R expression and pit patterns of polyps (r=0.432, p=0.002). Thus, IGF-1R might be a factor in the morphological change of colorectal mucosal crypts, and it may play an important role in the growth and malignant transformation of precancerous polyps. These results suggest that IGF-1R can be considered a biomarker for the stage and risk of carcinogenesis during neoplastic initiation and progression along the colorectal normal mucosa-polyp-cancer sequence. Inhibitors of IGF-1R are not only a promising targeted anticancer strategy, but also a possible option for the chemoprevention of colorectal cancer.

Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats.

AIM: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex (CSAR). METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA. RESULTS: The PVN microinjection of pro-inflammatory cytokines (PIC), tumour necrosis factor (TNF)-α or interleukin (IL)-1ß, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti-inflammatory cytokines (AIC), IL-4 or IL-13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF-α or IL-1ß but not in the rats pretreated with IL-4 or IL-13, sub-response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT(1) receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF-α and IL-1ß, but not the effects of IL-4 and IL-13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF-α, IL-1ß but not IL-4 in the PVN. CONCLUSION: TNF-α or IL-1ß in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT(1) receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1ß on blood pressure, sympathetic activity and CSAR.

Biological effects of a nano red elemental selenium.

A novel selenium form, nano red elemental selenium (Nano-Se) was prepared by adding bovine serum albumin to the redox system of selenite and glutathione. Nano-Se has a 7-fold lower acute toxicity than sodium selenite in mice (LD(50) 113 and 15 mg Se/kg body weight respectively). In Se-deficient rat, both Nano-Se and selenite can increase tissue selenium and GPx activity. The biological activities of Nano-Se and selenite were compared in terms of cell proliferation, enzyme induction and protection against free racial-mediated damage in human hepatoma HepG2 cells. Nano-Se and selenite are similarly cell growth inhibited and stimulated synthesis of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase (TR). When HepG2 cells were co-treated with selenium and glutathione, Nano-Se showed less pro-oxidative effects than selenite, as measured by cell growth. These results demonstrate that Nano-Se has a similar bioavailability in the rat and antioxidant effects on cells.

[Effects of a few nutritional factors on content of coenzyme Q10 by tobacco plant cells in suspension culture].

With suspension cultured cells of tobacco (Nicoliana Tobacum L.), effects of inorganic phosphate, nitrogen sources and carbon source on cell growth and CoQ10 content were investigated. It showed that, When treated with 30 g/L of sucrose, the total amount of CoQ10 was highest (8212 g/L); and the cell biomass and CoQ10 content were 19.8 micrograms/L, 414.7 micrograms/g(dwt) respectively. When treated 340 mg/L of KH2PO4, the cell biomass, the content and total amount of CoQ10 were 21.04 g/L, 514.5 micrograms/g(dwt) and 10824 micrograms/L respectively. When treated with the ratio of NH4+/NO3- was 1:2, the cell biomass, the content and total amount of CoQ10 were 21.04 g/L, 514.3 micrograms/g(dwt) and 10,820 micrograms/L respectively. The high ration of NH4+/NO3- was suitable for the formation of CoQ10, but not for the cell growth.