[Pre-operative prognostic nutritional index as a predictive factor for prognosis in non-metastatic renal cell carcinoma treated with surgery].

OBJECTIVE: To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII). METHODS: A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036). CONCLUSION: Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.

[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study.

BACKGROUND: This study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). PATIENTS AND METHODS: We identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses. RESULTS: ASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results. CONCLUSIONS: The findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4.

OBJECTIVE: Previous studies have shown that ubiquitin specific protease 3 (USP3) is an oncogene. However, the role of USP3 in non-small cell lung cancer (NSCLC) has not been reported. This study aims to explore the expression characteristics of USP3 in NSCLC, and its regulation on the proliferative capacity of NSCLC cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression levels of USP3 and RNA Binding Motif 4 (RBM4) in 42 pairs of tumor tissues and adjacent tissue specimens collected from NSCLC patients. Meanwhile, the correlation between the messenger ribonucleic acid (mRNA) expressions of USP3 and RBM4, and the clinical indicators and prognosis of NSCLC patients were analyzed. At the same time, mRNA expression of USP3 in NSCLC cell lines was further verified by the qRT-PCR method. In addition, USP3 knockdown and overexpression models were constructed using lentivirus in NSCLC cell lines H1299 and SPCA1. Cell counting kit-8 (CCK-8), cell colony formation, and 5-Ethynyl-2'-deoxyuridine (EDU) assays were performed to evaluate the influence of USP3 on proliferative capacity in NSCLC cells. Finally, Dual-Luciferase reporter assay and rescue experiments were conducted to further explore its underlying molecular mechanism. RESULTS: In this experiment, qRT-PCR results revealed that the expression level of USP3 in tumor tissues of NSCLC patients was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with NSCLC patients with low expression of USP3, those with high USP3 expression suffered much more advanced pathology stage and lower overall survival rate. Proliferation ability of NSCLC cells overexpressing USP3 was remarkably enhanced, while the opposite result was observed in the USP3 knockdown group. Subsequently, RBM4 expression in NSCLC tissue samples was found to be significantly reduced and negatively correlated with USP3 level. In addition, the result of Dual-Luciferase reporter assay demonstrated that USP3 can be targeted by RBM4. Rescue experiments revealed that RBM4 was responsible for NSCLC progression regulated by USP3. CONCLUSIONS: The above studies indicated that USP3 expression was remarkably up-regulated in NSCLC tissues, which was closely related to the pathological staging and poor prognosis of NSCLC patients. Therefore, USP3 might accelerate the proliferation of NSCLC cells via regulating RBM4.

Expression of duck hepatitis A virus type 1 VP3 protein mediated by avian adeno-associated virus and its immunogenicity in ducklings.

The avian adeno-associated virus (AAAV) is a replication-defective nonpathogenic virus that has been proved to be useful as a viral vector in gene delivery. In this study, the feasibility of AAAV for transgenic expression of duck hepatitis A virus (DHAV) VP3 structural protein and its ability to induce protective immunity in ducklings was assessed. The recombinant AAAV (rAAAV-VP3) expressing the VP3 protein was prepared by co-infection of Sf9 cells with recombinant baculovirus (rBac-VP3) containing VP3 gene flanked by inverted terminal repeats (ITRs) of AAAV and the other two recombinant baculovirus expressing AAAV functional and structural genes, respectively. The generation of rAAAV-VP3 was demonstrated by electron microscopy, immunofluorescence assay, and western blot analysis. One day old ducklings were inoculated with rAAAV-VP3 or commercial attenuated vaccine and then challenged with DHAV-1 strain SH two weeks post vaccination. Anti-DHAV-1 antibodies were detected in all vaccinated groups by ELISA, and the titers between the rAAAV-VP3 group and the attenuated vaccine group were not statistically significant. Real time RT-PCR analysis showed that the virus copy numbers in the livers of the PBS control group were significantly higher than that of the rAAAV-VP3 and attenuated vaccine groups. In conclusion, we demonstrated that the VP3 expression mediated by rAAAV in ducklings could induce protective immunity against DHAV challenge, and this could be a candidate vaccine for the control of duck viral hepatitis. Keywords: avian adeno-associated virus; duck hepatitis A virus; VP3 gene; immunogenicity.

Protection against duck hepatitis a virus type 1 conferred by a recombinant avian adeno-associated virus.

The avian adeno-associated virus (AAAV) has been proved to be an efficient gene transfer vector for human gene therapy and vaccine research. In this experiment, an AAAV-based vaccine was evaluated for the development of a vaccine against duck hepatitis a virus type 1 (DHAV-1). The major capsid VP1 gene was amplified and subcloned into pFBGFP containing the inverted terminal repeats of AAAV, and then the recombinant baculovirus rBac-VP1 was generated. The recombinant AAAV expressing the VP1 protein (rAAAV-VP1) was produced by co-infecting Sf9 cells with rBac-VP1 and the other 2 baculoviruses containing AAAV functional genes and structural genes respectively, and confirmed by electron microscopy, Western blotting and immunofluorescence assays. Quantitative real-time PCR revealed that the titer of rAAAV-VP1 was about 9 × 1012 VG/mL. Immunogenicity was studied in ducklings. One day ducklings were injected intramuscularly once with rAAAV-VP1. Serum from rAAAV-VP1-vaccinated ducklings showed a systemic immune response evidenced by VP1-specific enzyme-linked immunosorbent assay and virus neutralization test. Furthermore, all ducklings inoculated with rAAAV-VP1 were protected against DHAV-1 challenge. The data of quantitative real-time RT-PCR from livers of challenged ducklings also showed that the level of virus copies in rAAAV-VP1 group was significantly lower than that of the PBS group. Collectively, these results demonstrate that the AAAV-based vaccine is a potential vaccine candidate for the control of duck viral hepatitis.

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A (P>0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P<0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% (P=0.029) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P<0.05) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P<0.01) . The levels of estradiol in three groups were increased significantly (all P<0.01) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Peripheral Blood Leukocyte Telomere Length Is Associated with Age but Not Renal Function: A Cross-Sectional Follow-Up Study.

OBJECTIVES: We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese. METHODS: The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed. RESULTS: Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function. CONCLUSION: The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

Study on the expression of human lysozyme in oviduct bioreactor mediated by recombinant avian adeno-associated virus.

Due to its antimicrobial properties and low toxicity, human lysozyme (hLYZ) has broad application in the medical field and as a preservative used by the food industry. However, limited availability hinders its widespread use. Hence, we constructed a recombinant avian adeno-associated virus (rAAAV) that would specifically express hLYZ in the chicken oviduct and harvested hLYZ from the egg whites of laying hens. The oviduct-specific human lysozyme expression cassette flanked by avian adeno-associated virus (AAAV) inverted terminal repeats (ITRs) was subcloned into the modified baculovirus transfer vector pFBX, and then the recombinant baculovirus rBac-ITRLYZ was generated. The recombinant avian adeno-associated virus was produced by co-infecting Sf9 cells with rBac-ITRLYZ and the other 2 baculoviruses containing AAAV functional genes and structural genes, respectively. Electron microscopy and real-time PCR revealed that the recombinant viral particles were generated successfully with a typical AAAV morphology and a high titer. After one intravenous injection of each laying hen with 2 × 1011 viral particles, oviduct-specific expression of recombinant human lysozyme (rhLYZ) was detected by reverse transcription-PCR. The expression level of rhLYZ in the first wk increased to 258 ± 11.5 µg/mL, reached a maximum of 683 ± 16.4 µg/mL at the fifth wk, and then progressively declined during the succeeding 7 wk of the study. Western blotting indicated that the oviduct-expressed rhLYZ had the same molecular weight as the natural enzyme. These results indicate that an efficient and convenient oviduct bioreactor mediated by rAAAV has been established, and it is useful for production of other recombinant proteins.

Transgenic expression of ephrinB2 in periodontal ligament stem cells (PDLSCs) modulates osteogenic differentiation via signaling crosstalk between ephrinB2 and EphB4 in PDLSCs and between PDLSCs and pre-osteoblasts within co-culture.

BACKGROUND AND OBJECTIVE: The goal of periodontal therapy is to regenerate/reconstruct the damaged supporting tissues of diseased teeth and to facilitate recovery of their physiological functions. Combination of stem cell transplantation and gene therapy offers a viable method for accelerating periodontal repair and regeneration. In this study, the role of the ephrinB2/EphB4 signaling pathway in regulating osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and crosstalk between PDLSCs and pre-osteoblasts within co-culture was investigated through ephrinB2 transgenic expression in PDLSCs. MATERIAL AND METHODS: PDLSCs isolated from premolar teeth of teenage patients undergoing orthodontic treatment were transfected with transgenic (hEfnB2-GFP-Bsd) vector or empty vector (GFP-Bsd). Vector-PDLSCs, EfnB2-PDLSCs, MC3T3-E1 and co-cultures of vector-PDLSCs with MC3T3-E1, and EfnB2-PDLSCs with MC3T3-E1 were subjected to osteogenic induction. The osteogenic differentiation of EfnB2-PDLSCs, vector-PDLSCs and co-cultures were assessed by reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) assay and Alizarin-red S staining. Protein expression levels of ephrinB2, EphB4, phosphorylated ephrinB2 and EphB4 were analyzed by western blot, immunoprecipitation and co-immunoprecipitation assays. RESULTS: ALP assay and Alizarin-red S staining demonstrated higher ALP activity and increased mineralization with EfnB2-PDLSCs vs. vector-PDLSCs and with co-culture of EfnB2-PDLSCs and MC3T3-E1 vs. vector-PDLSCs and MC3T3-E1. Reverse transcription-polymerase chain reaction revealed that the expression of human odonto/osteogenic markers were significantly enhanced in EfnB2-PDLSCs compared to vector-PDLSCs, and that the expression of mouse odonto/osteogenic markers were significantly higher in co-culture of EfnB2-PDLSCs with MC3T3-E1 vs. vector-PDLSCs with MC3T3-E1. The EphB4 receptor was activated through phosphorylation during osteogenic differentiation. CONCLUSION: Our data indicate that transgenic expression of ephrinB2 in PDLSCs could promote osteogenic differentiation via stimulation of the phosphorylation of ephrinB2 and EphB4, which regulates cell communication between PDLSCs and between PDLSCs and pre-osteoblasts within co-culture.

Study to elucidate molecular mechanism behind zinc chemo-preventive role during lung carcinogenesis.

OBJECTIVE: The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. MATERIALS AND METHODS: The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks. RESULTS: The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc. CONCLUSIONS: The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis.

Anti-reflux anastomosis following esophagectomy for adenocarcinoma of the esophagogastric junction: impact of duodenogastroesophageal reflux and expression of cyclooxygenase-2 in the remnant esophagus.

OBJECTIVE: Reflux is the principal complication for patients after esophagectomy with gastric reconstruction. The aim of this study was to investigate the effect of the modified Nissen fundoplication after resection of adenocarcinoma from the esophagogastric junction (AEG) on controlling the reflux and the role of duodenogastroesophageal reflux (DGER) and cyclooxygenase-2 (COX-2) expression level in the remnant esophagus. PATIENTS AND METHODS: Sixty patients with AEG were randomly divided into two groups: (i) the conventional anastomosis group and (ii) the anti-reflux anastomosis group. Fifty esophagectomized patients were invited to participate in postoperative follow-up after 6 to 12 months. Among those we had 29 cases in the conventional anastomosis group and 21 in the anti-reflux anastomosis group. We used endoscopy, simultaneous 24 hours esophageal pH and bilirubin monitoring in this study. The COX-2 expression level in the remnant esophagus was detected using real-time PCR. RESULTS: The reflux esophagitis prevalence in anti-reflux anastomosis group was comparable to that in the conventional group (p = 0.154). DeMeester score and fraction time of bilirubin abs >0.14 decreased more intensely in the anti-reflux anastomosis group (p < 0.05). The COX-2 expression level in of anti-reflux anastomosis group was evidently lower than that in the conventional anastomosis group (p = 0.022) while it was meaningfully higher compared to the normal control group (p = 0.046). COX-2 up-regulation as well as high prevalence of esophagitis were observed in simultaneous acid reflux and DGER (p < 0.05). CONCLUSIONS: Although modified fundoplication following resection of AEG did not achieve an optimal effect on controlling reflux, it was very effective in decreasing the reflux. COX-2 expression monitoring can be considered as a possible new way to evaluate the impact of anti-reflux surgery. DGER occurring in acidic environment could develop severe reflux esophagitis and up-regulate the COX-2 expression.

IA comparison of two minimally invasive procedures for intra-articular displaced calcaneal fractures in older children.

The purpose of this study was to compare the clinical outcomes of displaced intra-articular calcaneal fractures in older children treated with poking reduction and cannulated screws fixation or with plate fixation using a sinus tarsi approach. From June 2008 to May 2012, fifty patients were randomised to operative stabilisation either by poking reduction and cannulated screws fixation (Group A, 28) or by plates fixation using a sinus tarsi approach (Group B, 22). The two groups were comparable with respect to age, gender, BMI, the affected side, cause of injury, fracture type, time from injury to surgery and follow-up time. We collected data on operative time and radiation time, length of hospitalization, hospital costs, union time, full weight-bearing time, full physical activity time and complications and measured joint function using the American Orthopaedic Foot and Ankle surgery (AOFAS) score. The average follow-up time of Group A was 36.5±9.3 months and 40.2±10.6 months in Group B. No significant difference between these two groups was found in radiation time, average length of hospitalization, union time, full weight-bearing time, full physical activity time and the average AOFAS score. However, the patients of Group B had longer operation time (38.0±10.6 min vs. 66.5±9.4 min, P<0.05) and more hospital costs (6200±800 RMB vs. 15000±2000 RMB, P<0.05). The average Bohler's angle and Gissane's angle preoperative were 10.9±5.3 and 141.3±12.1 in Group A, and became 31.2±5.1 and 128.5±5.4 after operation. The average Bohler's angle and Gissane's angle preoperative in Group B were 11.7±4.0 and 138.8±16.2, respectively, and they became 30.9±5.2 and 124.6±6.8 after operation. Bohler's angle and Gissane's angle were significantly restored after surgery (P<0.05). Postoperative incision pain was more frequent in Group B than in Group A (P<0.05). Our results indicated that both cannulated screws and plates were efficient methods for intra-articular calcaneal fractures in older children. However, poking reduction and cannulated screws fixation had the advantages of a shorter operative time, fewer hospital costs and less incision pain.

Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma, nasal-type: a multicenter study.

The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.

Construction of an integral formula of biological age for a healthy Chinese population using principle component analysis.

BACKGROUND: Whereas chronological age (CA) cannot distinguish functional differences among individuals of the same age, the biological age (BA) may be used to reflect the functional state of the body. The purpose of this study was to construct an integral formula of the BA, by using principle component analysis (PCA). METHODS: The vital organ function of 505 healthy individuals of Han origin (age 35-91 years) was examined. A total of 114 indicators of cardiovascular, pulmonary, and brain functions, and clinical, inflammatory, genetic, psychological, and life habit factors were assessed as candidate indicators of aging. Candidate indicators were submitted with CA to correlation and redundancy analyses. The PCA method was used to build an integral formula of the BA for the population. RESULTS: Seven biomarkers were selected in accordance with a certain load standard. These biomarkers included the trail making test (TMT), pulse pressure (PP), mitral valve annulus ventricular septum of the peak velocity of early filling (MVES), minimum carotid artery intimal-medial thickness (IMTmin), maximum internal diameter of the carotid artery (Dmax), maximal midexpiratory flow rate 75/25 (MMEF75/25), and Cystatin C (CysC). The formula for the BA was: BA = 0.0685 (TMT) + 0.267 (PP) - 1.375 (MVES) + 22.443 (IMTmin) + 2.962 (Dmax) - 2.332 (MMEF75/25) + 16.104 (CysC) + 0.137 (CA) + 0.492. CONCLUSION: Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.

Non-invasive assessment of liver fibrosis using real-time tissue elastography in patients with chronic hepatitis B.

AIM: To evaluate the utility of the elastic ratio calculated using real-time tissue elastography for assessing liver fibrosis in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS: Ninety-six patients with CHB were enrolled between September 2012 and August 2013. The elastic ratio of the liver for the intrahepatic venous small vessel was calculated to measure liver stiffness. Diagnostic performance of the elastic ratio and aminotransferase-to-platelet ratio index (APRI) were compared with histological fibrosis stage at liver biopsy. In addition, 45 healthy adult volunteers were participated in intra- and interobserver reliability studies. RESULTS: There was no significant influence of hepatitis B e antigen (HBeAg) status or hepatitis B virus DNA levels on the elastic ratio measurements in CHB patients. The elastic ratio was significantly correlated with histological fibrosis stage (r = 0.873, p < 0.001). Cut-off values were 2.62 for stage 2 and over (S ≥ 2), 3.20 for state 3 and over, and 3.86 for stage 4, respectively. The areas under the receiver operating characteristic (ROC) curves for elastic ratio and APRI diagnosis of significant fibrosis (S ≥ 2) was 0.91 (95% CI: 0.84-0.98) and 0.71 (95% CI: 0.57-0.86), and 0.94 (95% CI: 0.89-0.99) and 0.81 (95% CI: 0.71-0.91) for cirrhosis (S = 4), respectively. The elastic ratio measurements had good reproducibility: 0.838 for intra-observer reliability and 0.805 for inter-observer reliability, respectively (p < 0.001). CONCLUSION: Elastic ratio determined using real-time tissue elastography was an accurate and reproducible method for evaluating liver fibrosis in patients with CHB.

Staging of laryngeal carcinoma: comparison of high-frequency sonography and contrast-enhanced computed tomography.

AIM: To evaluate the accuracy of high-frequency sonography on pretherapeutic T-staging in patients with laryngeal carcinoma. MATERIALS AND METHODS: Thirty-six consecutive patients with laryngeal carcinoma undergoing surgical resection were included in this study. All patients underwent ultrasonographic examination and contrast-enhanced computed tomography before surgery. These imaging interpretations were evaluated independently and then compared with the reference of postoperative pathological examination. McNemar's test was used for comparing the data obtained separately from ultrasonography and computed tomography. RESULTS: There was one T2 stage tumour of an aryepiglottic fold undetected by sonography. Sonography failed to stage five tumours correctly; the T-staging accuracy was 83.3%. Contrast-enhanced computed tomography failed to stage four patients correctly; the T-staging accuracy was 88.8%. There was no difference between the pretherapeutic staging accuracy of ultrasonography and contrast-enhanced computed tomography (p=0.735). CONCLUSION: Ultrasonography has a reliable pretherapeutic staging accuracy of laryngeal carcinoma. It can be a non-invasive complementary technique for pretherapeutic staging of laryngeal carcinoma.