[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

[Detection of PIK3CA gene mutation and its related prognosis in colorectal cancer based on next-generation sequencing].

Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

Value of pelvic ultrasound combined with pituitary MRI in diagnosis of central precocious puberty in girls.

OBJECTIVE: This study aimed to investigate the value of pelvic ultrasound combined with pituitary magnetic resonance imaging (MRI) based on an artificial intelligence algorithm in the diagnosis of girls with central precocious puberty (CPP), providing reference for the prevention and control of CPP in girls. PATIENTS AND METHODS: 75 girls with CPP and 75 normal girls in Nantong First People's Hospital were studied. Pelvic ultrasound parameters were compared between the two groups based on an artificial intelligence algorithm. Pituitary MRI parameters were analyzed, and pituitary function parameters were explored. RESULTS: The results showed that the diagnostic sensitivity, specificity, and accuracy of the convolutional neural network (CNN) algorithm were 72.3%, 74.6%, and 78.3%, respectively. The sensitivity, specificity, and accuracy of CNN algorithm were significantly higher (p<0.05). The long diameter, anteroposterior diameter, and transverse diameter of the uterus in the precocious puberty (PP) group were significantly larger than those in the normal group (NG). The ovarian long diameter, ovarian anteroposterior diameter, and ovarian transverse diameter in PP group were significantly larger than those in NG. Uterine volume and ovarian volume in PP group were clearly higher than those in NG. The largest follicle diameter was clearly larger in PP patients than in NG patients. The coronal height, coronal width, sagittal height, and sagittal anteroposterior diameter of PP group were clearly higher than those of NG (p<0.05). The sagittal cross-sectional area of pituitary MRI morphology in PP group was significantly greater than that in NG. The pituitary MRI morphology pituitary volume was 272.68 mm in PP group and 191.37 mm in NG, and the pituitary volume was clearly larger in PP group than in NG. The pituitary function parameters estradiol (E2), luteinizing hormone (LH) peak, follicle-stimulating hormone (FSH) peak, and LH peak/FSH peak were greater in PP group than in NG. CONCLUSIONS: In summary, the uterine size and ovarian size of girls and the pituitary function index in PP group were larger. Pelvic ultrasound and pituitary MRI indexes can better diagnose CPP and can be widely used in clinical practice with positive diagnostic value.

[Survival analysis of unexpected small cell lung cancer following surgery].

Objective: To investigate the survival and influencing factors of unexpected small cell lung cancer following surgery. Methods: We respectively reviewed the clinical characters of 104 patients who underwent surgical treatment and be proved as small cell lung cancer by pathology between January 2000 to October 2020 in Chinese PLA General Hospital. Overall survival (OS) of patients was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Results: Of 104 patients, 27 cases showed central lesions, and other 77 showed peripheral nodules. The margin of nodules was smooth in 42 cases on CT imaging. The median OS was 34.3 months and 5-year OS rate was 45.8%. Postoperative 5-year OS rates for patients were 52.1%, 45.4%, and 27.8% for clinical stages Ⅰ, Ⅱ, and Ⅲ, respectively. Univariate analyses identified the age, surgical access, surgical approach, N stage, TNM stage and vascular cancer emboli were associated with OS (P<0.05). The N stage was an independent factor for the OS of patients (P<0.05). Conclusions: Patients with unexpected SCLC, including Ⅰ, Ⅱ and part ⅢA stage have favorable outcome and can benefit from surgery and systemic postoperative treatment. Standard lobectomy plus systemic lymph node dissection is commended.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

[Research progress on the correlation between small dense low-density lipoprotein-cholesterol and atherosclerotic cardiovascular disease].

Atherosclerotic cardiovascular disease (ASCVD), a series of cardiovascular diseases based on atherosclerosis, has attracted more clinical attention. However, with the increase of population-based research results, the diagnostic value of traditional blood lipid parameters such as low density lipoprotein-cholesterol (LDL-C) is showing limitations. In recent years, a large number of studies have confirmed that small dense low-density lipoprotein cholesterol (sdLDL-C) has lower affinity with low-density lipoprotein receptor, longer circulation time and easier to penetrate arterial endothelium, so it has stronger atherogenic effect. Therefore, we summarize the common detection methods of sdLDL-C, the research progress of the correlation between sdLDL-C and ASCVD risk, as well as the intervention measures and influencing factors of sdLDL-C level, in order to deepen the clinician's understanding of the role of sdLDL-C in ASCVD and achieve the early prevention, early detection and early diagnosis of chronic atherosclerosis.

[The combination of YAP/TAZ predicts the clinical prognosis in patients with cholangiocarcinoma after radical resection].

Objective: Cholangiocarcinoma (CCA) is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis. The Hippo-Yes-associated protein (YAP)/transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in cancer stem cell biology. Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes. We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients. Methods: CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016. Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining. The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model. Results: A total of 91 CCA patients were enrolled. During a median follow-up time of 11.0 months, 69.2% patients relapsed and 45.1% died. The median OS and DFS were 10.7 months and 8.8 months respectively. The YAP/TAZ dual positive patients owned a worse TNM stage (P=0.015), poorer tissue differentiation (P=0.007), and a higher CA199 than those in negative patients. Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS (P=0.010) and DFS (P=0.028) in CCA patients after radical resection. In subgroup analysis, YAP/TAZ combination also significantly predicted OS (P=0.044) and DFS (P=0.043) in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy. Conclusions: YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.

[Predicting response to non-small cell lung cancer immunotherapy using pre-treatment contrast-enhanced CT texture-based classification].

Objective: To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy. Methods: From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results: In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95%CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion: Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.

[Analysis of clinicopathological features of clear cell tumor of the lung].

Objective: To analyze the clinicopathological features of clear cell tumor of the lung (CCTL). Methods: A total of 9 cases were collected from August 2008 to August 2019 in the Department of Pathology of the First Medical Center of PLA General Hospital and Hainan Hospital of PLA General Hospital. Their clinical data, pathological characteristics, immunohistochemical staining and special staining results were summarized and analyzed. Results: There were 3 males and 6 females, aged from 28 to 70 years (average 52.2 years). All tumors were located in the peripheral part of the lung, and were solitary in 8 cases, and multiple (24 nodules) in 1 case. The lesion was round or oval, with clear boundary. The diameter of the nodule was 0.5-5.5 cm. Histologically, the tumor cells were oval, short fusiform or polygonal, with obvious nucleoli. The tumor cells were mostly distributed in sheet around thin-walled vessels, and there was hyaline degeneration around the blood vessels. Neither necrosis nor mitosis could be seen. Immunohistochemical staining showed tumor cells were diffusely positive for Vimentin, and CD34, Melan-A, specific monoclonal antibody against melanoma (HMB45) and S-100 were positive with different degrees. Broad spectrum cytokeratin (CK), epithelial membrane antigen (EMA), smooth muscle actin (SMA), desmin, CD10, paired box gene 8 (PAX-8) or myomodulatory protein (Myo-D1) were all negative. The positive index of the proliferating cell nuclear antigen (Ki-67) was low. Schiff dyeing with periodate (PAS) staining was positive, PAS staining of glycogen digested by amylase (d-PAS) staining was negative. All the tumors in the nine cases were resected and patients were followed up for 5-137 months. Except 1 case was lost for follow-up, the other 8 cases survived without recurrence or metastasis of the disease. Conclusions: CCTL is a rare benign tumor, most of which are single, few of which can be multiple; histopathological characteristics and immunohistochemical staining are helpful for diagnosis and differentiated diagnosis. After complete resection, the prognosis was good. However, when histological features indicating malignancy, intense follow-up should be considered.

Performance of BAC for DBPs precursors' removal for one year with micro-polluted lake water in East-China.

Effectiveness of biological activated carbon (BAC) filter in removing disinfection byproducts (DBPs) precursors of micro-polluted lake water for one year was conducted. The formation potential (FP) of DBPs (trihalomethanes (THMs), haloacetic acids (HAAs) and Nitrosamines (NAs)), dissolved organic carbon (DOC), molecular weight (MW) distribution and excitation emission matrix fluorescence (EEM) of dissolved organic material (DOM) in the influent and effluent of BAC were determined. The results indicated that the removal efficiency (RE) of DOC ranged from 42.9-28.3%. Neither virgin GAC nor long-term operated BAC could efficiently dispose of THMs and HAAs precursors (RE from 35.2-18.8%, from 42 to 8.4%, respectively), however, BAC still showed good ability in removal of NAs precursors after a year operation, of which RE just dropped from 81.7-69.6%. There was strong correlation between RE of NAs precursors and DOC with small MW (<0.5 kDa). The removal of HAAs precursors showed relatively close relation to aromatic protein-like components and soluble microbial pollutants (SMPs). Weak direct relationship was found between the water quality parameters and THMs precursors.

Taxonomy and phylogeny of Postia. Multi-gene phylogeny and taxonomy of the brown-rot fungi: Postia (Polyporales, Basidiomycota) and related genera.

Phylogenetic and taxonomic studies on the brown-rot fungi Postia and related genera, are carried out. Phylogenies of these fungi are reconstructed with multiple loci DNA sequences including the internal transcribed spacer regions (ITS), the large subunit (nLSU) and the small subunit (nSSU) of nuclear ribosomal RNA gene, the small subunit of mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α gene (TEF1), the largest subunit of RNA polymerase II (RPB1) and the second subunit of RNA polymerase II (RPB2). Ten distinct clades of Postia s.lat. are recognized. Four new genera, Amaropostia, Calcipostia, Cystidiopostia and Fuscopostia, are established, and nine new species, Amaropostia hainanensis, Cyanosporus fusiformis, C. microporus, C. mongolicus, C. piceicola, C. subhirsutus, C. tricolor, C. ungulatus and Postia sublowei, are identified. Illustrated descriptions of the new genera and species are presented. Identification keys to Postia and related genera, as well as keys to the species of each genus, are provided.

[Role and potential value of circular RNAs in the occurrence of primary hepatic cancer].

Circular RNA is a class of non-coding RNAs, which are covalently closed and circular at both ends, showing dissimilar characteristics from linear RNA. Several studies have shown that circular RNAs play an important role in the occurrence and development of primary hepatic cancer. By combining with the latest research progress of this field at home and abroad, we summarized the mechanism regulating the occurrence and development of liver cancer, abnormal expression, and as potential molecular markers for disease diagnosis and treatment.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.

Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease.

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aß) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aß-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.

[Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis].

Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo-RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo-RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28-0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis.

Glutathione S-transferase P1 rs1695 A>G polymorphism and breast cancer risk: evidence from a meta-analysis.

Breast cancer (BC) is the most widespread cause of cancer-related deaths in women. Many published studies have assessed the association between the glutathione S-transferase P1 (GSTP1) rs1695 polymorphism and BC risk. However, the effect of the GSTP1 rs1695 polymorphism on BC risk has remained controversial. Therefore, this meta-analysis was conducted to obtain a comprehensive estimation of this association. A total of 20,615 cases and 20,481 controls from thirty-six case-control trials were extracted from an online literature survey. The meta-analysis indicated that the GSTP1 rs1695 A>G polymorphism did not contribute to the susceptibility of BC when the overall population was considered. However, intriguingly, this polymorphism was significantly associated with increased risk of BC in Asian women [GG vs AA: odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.06-1.88, P = 0.02; AG vs AA: OR = 1.08, 95%CI = 1.00-1.16, P = 0.05; GG/AG vs AA: OR = 1.11, 95%CI = 1.04-1.19, P = 0.00]. Moreover, a subgroup analysis based on the source of control groups showed a marked increase in BC susceptibility in hospital-based control subjects (GG vs AA: OR = 1.28, 95%CI = 1.10-1.48, P= 0.00; GG vs AG/AA: OR = 1.22, 95%CI = 1.06-1.41, P = 0.00; GG/AG vs AA: OR = 1.10, 95%CI = 1.02-1.18, P = 0.00). In conclusion, our study indicated that the GSTP1 rs1695 A>G polymorphism was correlated with elevated BC risk in Asian women. Our results must be validated with further research.

Implicating the H63D polymorphism in the HFE gene in increased incidence of solid cancers: a meta-analysis.

A number of previous studies have demonstrated that the HFE H63D polymorphism is associated with increased risk of incidence multiple types of cancer, including colorectal cancer, breast cancer, liver cancer, pancreatic cancer, and gynecological malignant tumors. However, the clinical outcomes were inconsistent. Therefore, this meta-analysis was conducted to summarize the effect of the H63D variant on the incidence of solid tumor. PubMed and EMBASE databases were searched for articles associating the HFE H63D polymorphism with cancer risk. The relationships were evaluated by calculating the pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 28 studies, including 7728 cancer cases and 11,895 controls, were identified. Statistically significant associations were identified between the HFE H63D polymorphism and solid cancer risk (CG vs CC, OR = 1.14, 95%CI = 1.07-1.23, P < 0.001; GG vs CC, OR = 1.28, 95%CI = 1.06-1.55, P = 0.010; CG/GG vs CC, OR = 1.16, 95%CI = 1.08-1.24, P < 0.001; GG vs CC/CG, OR = 1.24, 95%CI = 1.02-1.49, P = 0.027). In the subgroup analysis, we illustrated the effect of the H63D polymorphism on hepatocellular carcinoma and pancreatic cancer risk, particularly in the Asian and African subgroups; however, this was not observed in gynecological malignant tumors. In summary, this analysis provided strong evidence that the HFE H63D polymorphism may play a critical role in the increased aggressiveness of hepatocellular carcinoma and pancreatic cancer.

Clinical significance of SHMT1 rs1979277 polymorphism in Asian solid tumors: evidence from a meta-analysis.

Published data regarding the association between the cytosolic serine hydroxymethyltransferase (SHMT1) C1420T (Leu474Phe) polymorphism and solid tumor risk have shown inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 23 published studies that included 14,409 cancer cases and 16,996 controls. A comprehensive search was conducted to identify all eligible studies of the SHMT1 rs1979277 polymorphism and solid tumor risk. The pooled odds ratios (ORs) and the 95% confidence intervals (95%CIs) were calculated using a fixed- or random-effects model. Heterogeneity was represented by PH; publication bias and sensitivity analysis were also explored. Overall, no significant associations were found for any genetic models tested. However, upon stratification by cancer type, a significant decreased risk of breast cancer risk was identified in the homozygote comparison (OR = 0.79, 95%CI = 0.65-0.97 for TT versus CC). An analysis stratified by ethnicity and source of controls revealed an obvious decrease in risk among Asian groups in all genetic models, and among population-based controls only in the homozygote comparison and recessive model. Therefore, our meta-analysis suggested that the SHMT1 C1420T polymorphism was associated with decreased risk of breast cancer. Significant protective effects were found among Asian populations, but not in Caucasian groups. Due to some minor limitations, our findings should be confirmed by further studies.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aß) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aß and mediates Aß-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aß. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aß deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aß deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing ß-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aß toxicity and would be a novel therapeutic target and biomarker for AD.