Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Identification of specific susceptibility loci for the early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely investigated. Here, we aimed to systematically identify specific susceptible genetic variants for EOCRC. METHODS: Two parallel GWASs were conducted in 17,789 CRC cases (including 1490 EOCRC cases) and 19,951 healthy controls. A polygenic risk score (PRS) model was built based on identified EOCRC-specific susceptibility variants by using the UK Biobank cohort. We also interpreted the potential biological mechanisms of the prioritized risk variant. RESULTS: We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10-4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model. Compared to the individuals in the low genetic risk group, the individuals in the high genetic risk group have increased EOCRC risk, and these results were replicated in the UKB cohort with a 1.63-fold risk (95% CI: 1.32-2.02, P = 7.67×10-6). The addition of the identified EOCRC risk loci significantly increased the prediction accuracy of the PRS model, compared to the PRS model derived from the previous GWAS-identified loci. Mechanistically, we also elucidated that rs12794623 may contribute to the early stage of CRC carcinogenesis via allele-specific regulating the expression of POLA2. CONCLUSIONS: These findings will broaden the understanding of the etiology of EOCRC and may facilitate the early screening and individualized prevention.

Circular RNA circ_0000423 promotes gastric cancer cell proliferation, migration and invasion via the microR-582-3p/Disheveled-Axin domain containing 1 axis.

For humans, gastric cancer (GC) is a common malignancy. Multiple circular RNAs (circRNAs) have been confirmed to be important cancer-promoting or tumor-suppressive factors. The present study discusses the roles and mechanisms of circ_0000423 in GC development. In this study, circ_0000423 expression in GC patient tissue samples and cell lines was detected via quantitative real-time polymerase chain reaction. Disheveled-Axin domain containing 1 (DIXDC1) expression in GC cells was examined via Western blot. Besides, cell counting kit-8 was utilized for detecting GC cell viability. GC cell migration and invasion were examined through Transwell assays. Bioinformatics and dual-luciferase reporter gene assays were employed to verify the regulatory relationships between microRNA-582-3p (miR-582-3p) and circ_0000423 or DIXDC1. In the present study, we demonstrated that circ_0000423 was highly expressed in GC. Circ_0000423 knockdown suppressed GC cell viability, migration and invasion. Moreover, miR-582-3p was confirmed as a direct target of circ_0000423, and an upstream regulator of DIXDC1. MiR-582-3p inhibition or DIXDC1 overexpression could reverse the above-mentioned effects of knocking down circ_0000423 on GC cells. In conclusion, circ_0000423 facilitates GC progression by modulating the miR-582-3p/DIXDC1 axis.

TRIM44 Promotes Colorectal Cancer Proliferation, Migration, and Invasion Through the Akt/mTOR Signaling Pathway.

PURPOSE: The tripartite motif protein 44 (TRIM44) participates in a variety of biological processes of malignant tumors. However, the expression and molecular mechanism of TRIM44 in colorectal cancer (CRC) remain unclear. PATIENTS AND METHODS: 123 CRC tissues were used for immunohistochemical assay and survival analysis. Small interfering RNA (siRNA) technology was used to silence the expression of TRIM44 in CRC cell lines. Then, we explored the effect of TRIM44 on the biological behavior of CRC cells. Finally, we studied the underlying mechanisms by Western blot. RESULTS: We found that TRIM44 is up-regulated in CRC tissues and cells. TRIM44 is a risk factor for poor prognosis in patients with CRC. In vitro, we effectively silenced the expression of TRIM44 in CRC cell lines. Silencing of TRIM44 inhibits the proliferation, migration and invasion of CRC cells. In terms of mechanistic studies, we found that high TRIM44 expression activates the Akt/mTOR signaling pathway. CONCLUSION: Our research showed that TRIM44 may serve as a biomarker for CRC patients.

Diagnostic Value Investigation and Bioinformatics Analysis of miR-31 in Patients with Lymph Node Metastasis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.

The prognosis role of AJCC/UICC 8th edition staging system in gastric cancer, a retrospective analysis.

OBJECTIVE: The present study was designed to investigate whether AJCC/UICC 8th edition staging system precisely differentiated patients with different prognosis of gastric cancer (GC). METHODS: There were 540 GC cases included in this study. Stratification was done according to the 7th and 8th AJCC/UICC tumor-node-metastasis (TNM) staging systems. Detailed comparison was conducted between two editions in terms of the sub-classification of pN3 stage, redefinitions of stage III, homogeneity, discrimination power, predictive accuracy, and complexity. RESULTS: Compared to the 7th edition, the 8th TNM staging system performed better by incorporating pN3a and pN3b into the final stage of GC (P<0.001), had better stage grouping homogeneity (P<0.001), prognostic value (area under the curve, AUC-value was 0.809), and comparable discrimination power. CONCLUSIONS: AJCC 8th TNM staging system showed improved efficiency in GC prognosis.

Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer.

PURPOSE: As mayor biomarkers in tumor microenvironment (TME), tumor associated macrophages (TAMs) of gastric cancer (GC) still needs further studies in terms of the number and distribution pattern. METHODS: Herein, tissue microarrays (TMA) incorporating 494 GC surgical samples in duplicate were stained for TAMs infiltration analysis. TAMs number was counted according to the locations, including infiltrating macrophages in cancer nest (MC), in invasive front (MF) and in stroma (MS). Correlations between TAMs number, distribution pattern and clinic-pathological features and survival analyses were performed. RESULTS: Infiltrating macrophages number in GC tissues was much higher than that in peritumoral tissues. TAMs number was not significantly correlated with the overall survival (OS). TAMs distribution pattern could be categorized into MC or MF/MS dominant pattern, and correlated with histological grade (P =0.001). The median OS of MF/MS dominant pattern (22.1, 95%CI: 23.5-28.9) was significantly shorter than that of MC dominant pattern (25.6, 95%CI: 28.5-35.6) (P =0.002). By receiver operating characteristic curve (ROC) analysis, the predictive value of TAMs distribution pattern was superior to histological grade and pM stage, but inferior to pN and TNM stage. CONCLUSIONS: TAMs distribution pattern could be an independent prognostic factor for the OS of GC patients, and patients with MF/MS dominant pattern had worse outcomes.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for peritoneal carcinomatosis from colorectal cancer: a systematic review and meta-analysis of current evidence.

OBJECTIVES: The therapeutic efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is still under debate. This meta-analysis and systematic review of published literature on this comprehensive strategy aims to evaluate its efficacy on CRC patients with PC. METHODS: A systemic review with meta-analysis of published literatures on treatment of CRS plus HIPEC for patients with PC from CRC was performed. In addition, a summary of study results of published literatures concerning CRS plus HIPEC treating patients with PC from CRC was also conducted. RESULTS: A total of 76 studies were selected, including 1 randomized controlled trial, 14 non-randomized controlled studies, and 61 non-controlled studies. The pooled hazard ratios (HRs) for overall survival (OS) in the 15 researches for meta-analysis was 2.67 (95% CI, 2.21-3.23, I2= 0%, P < 0.00001), and no significant evidence of publication bias was found. The difference of chemotherapy regimens of HIPEC was not associated with OS and DFS (disease-free survival) after CRS and HIPEC, with no significant difference of heterogeneity (P = 0.27, I2 = 24.1%). In both groups of mitomycin C based HIPEC group and oxaliplatin group, patients received HIPEC had significant better survival (P < 0.00001). The mean mortality and morbidity for HIPEC program were 2.8% and 33.0%, respectively. CONCLUSIONS: This meta-analysis revealed that comprehensive therapeutic strategy of CRS plus HIPEC could bring survival benefit for selected patients with PC from CRC with acceptable safety.

CDK5RAP3 acts as a tumor suppressor in gastric cancer through inhibition of ß-catenin signaling.

CDK5RAP3 was isolated as a binding protein of the Cdk5 activator p35. Although CDK5RAP3 has been implicated in cancer progression, its expression and function have not been investigated in gastric cancer. Our study demonstrated that the mRNA and protein levels of CDK5RAP3 were markedly decreased in gastric tumor tissues when compared with respective adjacent non-tumor tissues. CDK5RAP3 in gastric cancer cells significantly reduced cell proliferation, migration, invasion and tumor xenograft growth through inhibition of ß-catenin. Secondly, CDK5RAP3 was found to suppress the phosphorylation of GSK-3ß (Ser9), leading to the phosphorylation (Ser37/Thr41) and subsequent degradation of ß-catenin. Lastly, the prognostic value of CDK5RAP3 for overall survival was found to be dependent on ß-catenin cytoplasm/nucleus localization in human gastric cancer samples. Collectively, our results demonstrated that CDK5RAP3 negatively regulates the ß-catenin signaling pathway by repressing GSK-3ß phosphorylation and could be a potential therapeutic target for gastric cancer.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel improves survival for patients with peritoneal carcinomatosis from abdominal and pelvic malignancies.

BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.

Long noncoding RNA HULC promotes colorectal carcinoma progression through epigenetically repressing NKD2 expression.

Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, and facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database.

BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

Oral gastrografin radiography for the evaluation of the functional impact of peritoneal carcinomatosis: Correlation with clinicopathological findings.

This study was conducted to evaluate the functional impact of peritoneal carcinomatosis (PC) on the gastrointestinal system by oral gastrografin radiography (OGR). OGR was performed on 105 patients with PC from abdominal malignancies. The OGR characteristics were analyzed and compared with intraoperative observations. OGR provided real-time dynamic information on the functional impacts of PC. The OGR findings were normal in 9 (8.6%) and abnormal in 96 (91.4%) cases. In terms of frequency, 33 cases (31.4%) exhibited mild intestinal aggregation and flattening of the intestinal mucosa; 29 cases (27.6%) exhibited limited intestinal invasion, marginally stenotic small bowel and mucosal deformities; 26 cases (24.8%) exhibited only mild mesenteric contracture and mild slowing of gastrointestinal peristalsis; 5 cases (4.8%) exhibited obvious mesenteric contracture, ball-like changes, fixed position and disappearance of the intestinal mucosa; 2 cases (1.9%) exhibited complete pyloric obstruction; and 1 case (0.9%) exhibited duodenal obstruction. Gastric PC was associated with a higher percentage of stomach filling defects and small intestinal aggregates compared with PC from other malignancies (P<0.01 for both). In 87 cases, the ORG findings were in accordance with the intraoperative findings (κ=0.726, P<0.001), whereas 17 cases (16.2%) were underestimated and 1 (0.9%) was overestimated by OGR. This study indicated that OGR may be a useful technique for the evaluation of the functional impacts of PC on the gastrointestinal system and may help optimize the selection of patients for treatment.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: a phase II study from a Chinese center.

BACKGROUND: Peritoneal carcinomatosis (PC) is a difficult clinical challenge in colorectal cancer (CRC) because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC. METHODS: A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS), and the secondary end points were perioperative safety profiles. RESULTS: By the most recent database update, the median follow-up was 29.9 (range 3.5-108.9) months. The peritoneal cancer index (PCI) ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1) was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2-19.8) months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit. DISCUSSION: CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.

Intraperitoneal chemotherapy for peritoneal carcinomatosis improves efficacy with acceptable safety: results of 200 cycles for 41 patients.

BACKGROUND/AIMS: To investigate the efficacy and safety of intraperitoneal (IP) chemotherapy for peritoneal carcinomatosis (PC). METHODOLOGY: Forty-one PC patients received IP chemotherapy with carboplatin at 200 mg/m2 and docetaxel at 60 mg/m2 at 21-day intervals. Major organ functions were monitored. Changes in ascites and serum tumor markers (TM) were recorded. The primary endpoint was overall survival COS) and the secondary endpoint was adverse event (AE). RESULTS: The patients received 200 cycles of IP chemotherapy, with a median of 5 IP chemotherapy cycles at the median duration of 5 months. The median follow-up was 19.5 months. For 25 patients with ascites, 15 cases had significant improvement, 9 had stable disease, and 1 had treatment failure. End-point events occurred in 31 patients, including 26 deaths from gastrointestinal PC with a median OS of 8.4 months (95%CI 4.6-12.2 months) and 5 deaths from other origins (median OS not reached). Multivariate analysis revealed the following independent OS-related factors: CC<1, primary tumor site, and decreases in CA125 and CEA for 2 consecutive cycles. Grade III toxicities included 16 cycles of digestive AE and 8 cycles of bone marrow suppression. CONCLUSIONS: IP chemotherapy improves OS for PC patients with acceptable safety.

The relationship between vitamin A and risk of fracture: meta-analysis of prospective studies.

Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta-carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta-analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I(2) statistic to assess heterogeneity and Egger's test to assess publication bias. Eight vitamin A (or retinol or beta-carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta-carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]). Both high or low level of blood retinol was shown to increase the risk of hip fracture (adj.RR [95% CI] = 1.87 [1.31, 2.65] and 1.56 [1.09, 2.22], respectively). The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose-response meta-analysis shows a U-shaped relationship between serum retinol level and hip fracture risk. Our meta-analysis suggests that blood retinol level is a double-edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta-carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: a case-control study from a Chinese center.

BACKGROUND: Advanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case-control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC. METHODS: The 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles. RESULTS: For the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0-1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7-12.4) versus 13.7 (95% CI 10.0-16.5) months (P = 0.02), the 1-, 2-, and 3-year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0-1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit. CONCLUSION: CRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety.

Subtype B was the dominant strain among HIV type 1 infections except for the population of men who have sex with men in Harbin City, China.

We sought to identify the prevalent subtypes and study the genetic variation of HIV-1 circulating in HIV infections in Harbin City, China. Forty-seven samples from the env V3-V4 region were successfully sequenced and analyzed, which involved thirty-one men who have sex with men (MSM), eight heterosexuals, seven former plasma donors (FPD)/blood transfusion recipients (BT), and one injection drug user (IDU). In all, 46.8% of CRF01_AE, 40.4% of subtype B, and 12.8% of CRF07_BC were identified. CRF01_AE (64.5%) was the dominant strain in MSM, and subtype B (81.2%) was the chief strain in other infected subjects except for the MSM population. Among all the genotypes, the B subtype possesses greater diversity of the tetramer on the tip of V3 loop than CRF07_BC and CRF01_AE, in which the peculiar GWGR was commonly found. Because nationwide there is a trend toward the increasing presence of CRF01_AE, a consecutive surveillance campaign was necessary among all HIV vulnerable populations in this locality.

Analysis of human immunodeficiency virus type 1 Vif gene sequences among men who have sex with men in Heilongjiang province of China.

To identify the current prevalent subtypes and to study the genetic variation of HIV-1 strains in men who have sex with men (MSM) residing in Heilongjiang province, China. We analyzed the characteristics of the nucleotide sequences and the corresponding deduced protein of Vif of HIV-1 strains isolated from 17 drug-naive HIV-1-seropositive MSM. Subtypes B (7.65%) and B' (Thailand B) (11.76%), CRF07_BC (47.06%), and CRF01_AE (23.53%) were identified. Phylogenetic analysis showed that there was a close relationship between our strains and those from the same MSM population in Hebei province, which is geographically close to Heilongjiang. Most of the documented Vif functional motifs are well conserved in the majority of our analyzed sequences. Taken together, our results suggest that there might be multiple introductions of HIV in Heilongjiang MSM and frequent sexual communications with other geographically nearby MSM populations.

[Asymmetric control method for ion shutter and the resolution improvement of ion mobility spectrum].

In order to change the driving mode of ion shutter, simplify the design of ion shutter driving power and improve the resolution of ion mobility spectrometry, a series of resistors were added to achieve asymmetric power supply of ion shutter, and the low voltage part was controlled to realize the function of ion shutter. Two conditions in this mode, the effect of electric field in drift tube and the resolution and signal-to-noise ratio of ion mobility spectrum were analyzed. Aided by SIMION 7.0, the electric field distribution at both sides of ion shutter was simulated and compared. Electric field data of drift tube axis was calculated through the method of numerical solution of Laplace equation. Experiment has proved that: compared with floating ground driving power used in conventional ion mobility spectrometry, the driving mode was low cost, and the design of ion shutter driving power supply was simple, and the resolution of ion mobility spectrometry was enhanced significantly. The method can be used in measurement instrument or experimental device of ion mobility spectrometry.