Rescue therapy with an albuvirtide-based antiretroviral regimen in an HIV-infected child with multidrug resistance and multiple opportunistic infections: a case report.

BACKGROUND: Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains. CASE PRESENTATION: A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions. CONCLUSIONS: The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children.

Expression level of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) of patients with NSCLC as an early indicator to monitor the effects of postoperative adjuvant chemotherapy.

BACKGROUND: An early indicator for monitoring the effect of adjuvant treatment after lung cancer surgery is urgently needed. The study was to explore the effects of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) in NSCLC patients with postoperative adjuvant chemotherapy. METHODS: Two drugs (platinum-containing chemotherapeutics + platinum-free chemotherapeutics) first-line chemotherapy regimen were given after surgery. MRNA of EpCAM was detected. Chest computed tomography, head computed tomography and abdominal B-ultrasound were reviewed before the first and third chemotherapy. RESULTS: EpCAM in CTCs from peripheral blood between the recurrent group and the non-recurrent group at 1 day before surgery, first, second and third adjuvant chemotherapy were no significant differences (P>0.05). Only one day before the fourth adjuvant chemotherapy treatment, it showed significant difference between the recurrent group and the non-recurrent group (P=0.008). There was a significant difference between the time of imaging diagnosis of recurrence or metastasis and the time of monitoring the expression level of EpCAM in CTCs from peripheral blood (P<0.0001). CONCLUSIONS: EpCAM in CTCs from peripheral blood during postoperative adjuvant chemotherapy was related to recurrence or metastasis of NSCLC patients.

Screening, identification and validation of CCND1 and PECAM1/CD31 for predicting prognosis in renal cell carcinoma patients.

Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide. Despite intense efforts to elucidate its pathogenesis, the molecular mechanisms and genetic characteristics of this cancer remain unknown. In this study, three expression profile data sets (GSE15641, GSE16441 and GSE66270) were integrated to identify candidate genes that could elucidate functional pathways in ccRCC. Expression data from 63 ccRCC tumors and 54 normal samples were pooled and analyzed. The GSE profiles shared 379 differentially expressed genes (DEGs), including 249 upregulated genes, and 130 downregulated genes. A protein-protein interaction network (PPI) was constructed and analyzed using STRING and Cytoscape. Functional and signaling pathways of the shared DEGs with significant p values were identified. Kaplan-Meier plots of integrated expression scores were used to analyze survival outcomes. These suggested that FN1, ICAM1, CXCR4, TYROBP, EGF, CAV1, CCND1 and PECAM1/CD31 were independent prognostic factors in ccRCC. Finally, to investigate early events in renal cancer, we screened for the hub genes CCND1 and PECAM1/CD31. In summary, integrated bioinformatics analysis identified candidate DEGs and pathways in ccRCC that could improve our understanding of the causes and underlying molecular events of ccRCC. These candidate genes and pathways could be therapeutic targets for ccRCC.

ß-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition.

Glioblastoma is the most common malignant brain tumor and has a poor prognosis. Tachykinin receptor neurokinin-1 (NK1R) is a promising target in glioblastoma therapy because of its overexpression in human glioblastoma. NK1R agonists promote glioblastoma cell growth, whereas NK1R antagonists efficiently inhibit cell growth both in vitro and in vivo However, the molecular mechanisms involved in these effects are incompletely understood. ß-Arrestins (ARRBs) serve as scaffold proteins and adapters to mediate intracellular signal transduction. Here we show that the ARRB1-mediated signaling pathway is essential for NK1-mediated glioblastoma cell proliferation. ARRB1 knockdown significantly inhibited NK1-mediated glioblastoma cell proliferation and induced G2/M phase cell cycle arrest. ARRB1 knockdown cells showed remarkable down-regulation of CDC25C/CDK1/cyclin B1 activity. We also demonstrated that ARRB1 mediated prolonged phosphorylation of ERK1/2 and Akt in glioblastoma cells induced by NK1R activation. ERK1/2 and Akt phosphorylation are involved in regulating CDC25C/CDK1/cyclin B1 activity. The lack of long-term ERK1/2 and Akt activation in ARRB1 knockdown cells was at least partly responsible for the delayed cell cycle progression and proliferation. Moreover, we found that ARRB1-mediated ERK1/2 and Akt phosphorylation regulated the transcriptional activity of both NF-κB and AP-1, which were involved in cyclin B1 expression. ARRB1 deficiency increased the sensitivity of glioblastoma cells to the treatment of NK1R antagonists. Taken together, our results suggest that ARRB1 plays an essential role in NK1R-mediated cell proliferation and G2/M transition in glioblastoma cells. Interference with ARRB1-mediated signaling via NK1R may have potential significance for therapeutic strategies targeting glioblastoma.

The clinicopathological significance of RUNX3 hypermethylation and mRNA expression in human breast cancer, a meta-analysis.

Aberrant promoter methylation of RUNX3 has been reported in several tumors including human breast cancer (BC). However, the association between RUNX3 hypermethylation and incidence of BC remains elusive. In this study, a detailed literature search was performed in Medline and Google Scholar for related research publications. Analysis of pooled data were executed. Odds ratios with corresponding confidence intervals were determined and summarized, respectively. Finally, 13 studies were identified for the meta-analysis. Analysis of the pooled data showed that RUNX3 hypermethylation was significantly higher in both ductal carcinoma in situ and invasive ductal carcinoma (IDC) than in normal breast tissues. In addition, RUNX3 methylation was significantly higher in IDC than in benign tumor. However, RUNX3 methylation was not significantly higher in IDC than in ductal carcinoma in situ. We also determined that RUNX3 hypermethylation was significantly higher in ER positive BC than in ER negative BC. In addition, high RUNX3 mRNA expression was found to be correlated with better overall survival and relapse-free survival for all BC patients. Our results strongly support that RUNX3 hypermethylation may play an important role in BC incidence. RUNX3 methylation is a valuable early biomarker for the diagnosis of BC. Further large-scale studies will provide more insight into the role of RUNX3 hypermethylation in the carcinogenesis and clinical diagnosis of BC patients.

Research on the relationship between serum levels of inflammatory cytokines and non-small cell lung cancer.

AIMS: This study was conducted to evaluate the levels of TNF-α, IL-6, IL-8 and VEGF in serum of patients with non- small cell lung cancer, for assessing their possible diagnostic and prognostic roles. METHODS: We enrolled 48 patients newly diagnosed with non-small cell lung cancer and 40 healthy controls. TNF- α, IL-6 and IL-8 levels were measured in the serum of all the subjects with specific radioimmunoassay kits, while EGF was analyzed by sandwich enzyme immunoassay techniques. RESULTS: A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-α, IL-6, IL-8 and VEGF in serum. Moreover, TNF-α, IL-8 and VEGF levels were higher in patients with advanced stages compared to early stages. In addition, higher serum levels of TNF-α, IL-6, IL-8 and VEGF were found in smokers than in non-smokers, both in patients and controls. CONCLUSION: Serum levels of TNF-α, IL-6, IL-8 and VEGF were all elevated in lung cancer patients, suggesting that inflammatory cytokines could be jointly used as a screening tool. Though TNF-α, IL-8 and VEGF levels were related to advanced disease, long-term survival studies of NSCLC patients should be performed to confirm whether they can act as biomarkers of advanced disease. In addition, smoking would be an important contributor to the processes of inflammation and lung cancer.

[Video-assisted thoracoscopic surgery bronchial sleeve lobectomy for lung cancer].

OBJECTIVE: To discuss the feasibility of video-assisted thoracoscopic surgery(VATS) bronchial sleeve lobectomy for NSCLC,and to describe this treatment method and the major Indications. METHOD: Between September 2010 and December 2012, 10 patients in our hospital underwent VATS bronchial sleeve lobectomy.The patients were one female and nine males.Included 3 cases on the right upper lobe, 3 cases on the right lower lobe, 1 case on the right middle lobe, 2 cases on the left upper lobe, 1 case on the left lower lobe.2 cases underwent VATS bronchial sleeve lobectomy and sleeve resection of the pulmonary artery. RESULTS: 10 cases were finished by Video-Assisted Thoracoscopic Surgery.They all recovered well.No patient showed bronchopleural fistula, empyema and atelectasis.There was no perioperative death. CONCLUSIONS: Video-assisted thoracoscopic surgery (VATS) lobectomy including bronchial sleeve lobectomy is therefore considered to be a feasible surgical modality for the treatment of patients with NSCLC.

[Epidemiological study on hyperuricemia and gout in Uygur population in Turpan area of Xinjiang].

OBJECTIVE: To study the prevalence of hyperuricemia (HUA) and gout in Uygur inhabitants in Turfan of Xinjiang. METHODS: A random cluster sampling was conducted, and 3 982 Uygur inhabitants(1 745 males and 2 237 females) aged over 14 years were investigated for prevalence of HUA and gout in Turfan. RESULTS: (1) The mean level of serum uric acid (SUA) was (284.33±88.81)µmol/L in normal Uygur males and (201.04±66.30)µmol/L in normal Uygur females in Turfan. (2) The prevalence of HUA was 3.97%(158/3 982),in which 6.36% (111/1 745) was with males and 2.10%(47/2 237) with females. The prevalence of gout was 0.025% (1/3 982),one gout patient was male, and the prevalence of gout in males was 0.06% (1/1 745). CONCLUSION: The prevalence rates of HUA and gout among the Uygur population in Turfan of Xinjiang were lower than those in other districts in China.

[Effects of serum containing Fructus Cnidii and Psoralea corylifolia on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2].

OBJECTIVE: To explore the effects of different proportions of Fructus Cnidii (Shechuangzi) and Psoralea corylifolia (Buguzhi) on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2 in vitro. METHODS: Thirty-six female SD rats were randomly divided into 6 groups to prepare the drug-medicated sera by administering with different proportions of Fructus Cnidii and Psoralea corylifolia, including 4:0 group, 3:1 group, 1:1 group, 1:3 group, 0:4 group and control group. MDA-MB-231BO cells and ST-2 cells were cultured in Dulbecco's modified Eagle's medium containing drug-medicated serum. Inhibition rates of MDA-MB-231BO cells and ST-2 cells were measured by methyl thiazolyl tetrazolium (MTT) method; migration ability of MDA-MB-231BO cells was tested by a cell migration experiment; alkaline phosphatase activity (ALP) of ST-2 cells was measured by using 4-nitrophenyl phosphate disodium salt, and mineralized nodule formation of ST-2 cells was measured by alizarin red staining. RESULTS: Sera contaning different proportions of Fructus Cnidii and Psoralea corylifolia inhibited the migration activity of MDA-MB-231BO cells as compared with the blank serum, and serum contaning Fructus Cnidii and Psoralea Corylifolia at proportion of 1:1 had the best function (P<0.01). Fructus Cnidii and Psoralea corylifolia at ratio of 1:1 also enhanced the ALP activity of ST2 cells (P<0.05) and increased the number of mineralized nodules of ST2 cells (P<0.01). CONCLUSION: Kidney-warming recipe of Fructus Cnidii and Psoralea corylifolia can inhibit proliferation and migration of MDA-MB-231BO cells and increase the activity of ST-2 cells.

Dietary intake of lead and cadmium by children and adults - Result calculated from dietary recall and available lead/cadmium level in food in comparison to result from food duplicate diet method.

The dietary intakes of lead and cadmium by 30 children and 30 adults living in Jinhu area in China were determined by the duplicate method with a 3-day sampling period. Dietary recall and available lead/cadmium level in food were also used to calculate dietary intakes. Lead intakes based on duplicate method were 15.66µg(kg(bw))(-1)week(-1) for children and 8.83µg(kg(bw))(-1)week(-1) for adults. Cadmium intakes were 2.07µg(kg(bw))(-1)week(-1) for children and 1.49µg(kg(bw))(-1)week(-1) for adult. The results from the dietary record method were as follows: lead intakes were 11.84µg(kg(bw))(-1)week(-1) for children and 7.70µg(kg(bw))(-1)week(-1) for adult. Cadmium intakes were 2.20µg(kg(bw))(-1)week(-1) for children and 1.44µg(kg(bw))(-1)week(-1) for adults. Children's dietary intakes were higher than those of adults'. The results of the dietary intakes calculated from two methods did not have significant difference. Compared to the FAO/WHO PTWIs for lead and cadmium, the average lead and cadmium dietary intakes are all below PTWIs. It was concluded that dietary record method can give comparatively accurate result for lead and cadmium dietary intakes compared with duplicate method. The average lead and cadmium dietary intakes for children and adults in Jinhu area are considered safe. However, the high level of dietary lead and cadmium intakes of children in this area deserves our attention.

[Resident dietary exposure of cadmium in Jiangsu province].

OBJECTIVE: To investigate the resident dietary cadmium exposure in Jiangsu province and assess its safety. METHODS: Cadmium concentration of 229 food items under 12 food groups were obtained from the food surveillance program in Jiangsu province between 2001 and 2006. Food consumption data of 778 food items of 3938 residents who were classified into four age groups (< 7, 7-, 13-, 18-) were got from the Nutrition and Health Status Survey of the Jiangsu resident in 2002 by 24 h dietary recall on three consecutive days. Dietary cadmium exposures for the residents of different age groups were obtained by using both point estimation and simple distribution estimation through integrating the two datasets above. The safety of dietary cadmium exposure was assessed. RESULTS: Point estimation showed that the average dietary cadmium intakes of different age groups ranged from 5.7 to 8.6 microg/kg, accounting for 567.1% - 857.1% of the provisional tolerable daily intake (PTDI, 1.0 microg/kg). Result of simple distribution method showed mean daily cadmium exposure of different age groups ranged from 0.2 to 0.4 microg/kg, accounting for 20% - 40% of PTDI. Mean weekly cadmium exposure ranged from 1.4 to 2.5 microg/kg, accounting for 20% - 35.7% of the provisional tolerable weekly intake (PTWI, 7.0 microg/kg). The mean daily dietary cadmium exposure for different groups were as follows: < 7, 0.4 microg/kg; 7-, 0.3 microg/kg; 13-, 0.2 microg/kg; 18-, 0.2 microg/kg. Differences of daily dietary cadmium exposures among groups were significant (F = 69.0, P < 0.05). The mean weekly dietary cadmium exposure for different groups were: < 7, 2.5 microg/kg; 7-, 2.0 microg/kg; 13-, 1.4 microg/kg; 18-, 1.4 microg/kg. Differences of weekly dietary cadmium exposures among groups were also significant (F = 41.6, P < 0.05). The P97.5 of daily cadmium exposure for < 7 and 7- were 1.4 and 1.2 microg/kg, respectively, both of which were higher than PTDI. The P99.0 of daily cadmium exposure for 13- and 18- were 1.3 and 1.1 microg/kg, respectively. The daily dietary exposure from cereals for different age groups were 21.5 - 253.4 microg/kg, occupying 42.2% - 47.8% of the total daily exposure. Vegetables were 8.0 - 119.4 microg/kg, occupying 14.6% - 20.1%. CONCLUSION: The average level of dietary cadmium exposures for residents in Jiangsu province calculated by simple distribution estimation were much lower than that calculated by point estimation and were considered to be at no risk. P97.5 or P99.0 of daily or weekly dietary cadmium exposure of different age groups exceeded PTWI and PTDI. The main food types of dietary cadmium exposure were cereals and vegetables.

[Application of vascular surgery in the treatment of thoracic neoplasm].

OBJECTIVE: To investigate superior vena cava (SVC) and anonymous vein resection with prosthesis replacement for lung carcinoma and mediastinal tumor, and to assess the surgical procedure and prognosis. METHODS: Experimental research: Eighteen adult dogs were divided randomly into two groups. Group A (n = 9) underwent blocking of the SVC system, and Group B (n = 9) underwent SVC resection with prosthesis replacement. The SVC pressure and histological changes of brain tissue were measured and evaluated for group A. The histological changes of prosthesis were studied in group B. Clinical research: Fifty-six patients with thoracic neoplasm were studied, of which 42 were lung carcinoma and 14 were mediastinal tumor. Resection of primary lesions and metastatic lymph nodes with replacement of SVC system were performed for all patients. Long-term follow-up was performed. RESULTS: Experimental research: In Group A, the pressure of SVC was higher when both SVC and the azygous vein were blocked as compared to SVC blocking only (P < 0.05); hyperemia and edema of brain tissue were not observed in two-hour obstruction. The inner face of vascular prosthesis was covered with fibrin two months after operation in group B. Vascular endothelial cells were found to grow in it, and there was no thrombosis without anticoagulation. Clinical research revealed that there was no death associated with the operation and there was no early or late obstruction of SVC. The survival rates of the patients with lung carcinoma in 1, 3 and 5 years were 84.2% 40.9% and 38.9% respectively. The patients with mediastinal tumor were all alive except 1 patient who died of metastasis. CONCLUSIONS: Radical resection combined with prosthesis replacement of SVC system extends the indications of thoracic neoplasm resection and improve the long-term survival rate and living qualities of the patients. It may be recommended in the surgical treatment of thoracic tumor.