Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.

PURPOSE: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. METHODS: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. RESULTS: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42). CONCLUSION: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy. TRIAL REGISTRY: The clinical trial registration number: ChiCTR2300076883.

"Caudal to cranial" versus "medial to lateral" approach in laparoscopic right hemicolectomy with complete mesocolic excision for the treatment of stage II and III colon cancer: perioperative outcomes and 5-year prognosis.

The purpose of this study was to compare the "caudal to cranial" (CC) versus "medial to lateral" (ML) approach for laparoscopic right hemicolectomy. Pertinent data from all patients with stage II and III between January 2015 and August 2017 were entered into a retrospective database. A total of 175 patients underwent the ML (N = 109) or CC approach (N = 66). Patient characteristics were equivalent between groups. The CC group showed a shorter surgical time 170.00 (145.00, 210.00) vs. (206.50 (178.75, 226.25) min) than the ML group (p < 0.001). The time to oral intake was shorter in the CC group than in the ML group ((3.00 (1.00, 4.00) vs. 3.00 (2.00, 5.00) days; p = 0.007). For the total harvested lymph nodes, there was no statistical significance between the CC group 16.50 (14.00, 21.25) and the ML group 18.00 (15.00, 22.00) (p = 0.327), and no difference was found in the positive harvested lymph nodes (0 (0, 2.00) vs. 0 (0, 1.50); p = 0.753). Meanwhile, no differences were found in other perioperative or pathological outcomes, including blood loss and complications. For 5-year prognosis, overall survival rates were 75.76% in the CC group and 82.57% in the ML group (HR 0.654, 95% CI 0.336-1.273, p = 0.207); disease-free survival rates were 80.30% in the CC group and 85.32% in the ML group (HR 0.683, 95% CI 0.328-1.422, p = 0.305). Both approaches were safe and feasible and resulted in excellent survival. The CC approach was beneficial in terms of the surgical time and time to oral intake.

Preimplantation genetic testing for human blastocysts with potential parental contamination using a quantitative parental contamination test (qPCT): an evidence-based study.

RESEARCH QUESTION: Is it possible to develop a quantitative method for detecting parental DNA contamination in conventional IVF using preimplantation genetic testing for aneuploidy (PGT-A)? DESIGN: In this study, a quantification method was established for the parental contamination test (qPCT), which ensured more reliable results, and then verified its effectiveness for vitrified conventional IVF embryos. A total of 120 surplus vitrified blastocysts from patients who underwent prior routine IVF cycles were available for study. RESULTS: The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and that the risk of paternal contamination was negligible. The 24 frozen embryo transfer cycles resulted in 16 clinical pregnancies, including 13 live births, one late inevitable miscarriage and two ongoing pregnancies. CONCLUSIONS: The risk of PGT in embryos with potential parental contamination is relatively low, and PGT-A is applicable for vitrified conventional IVF embryos.

CENPO regulated proliferation and apoptosis of colorectal cancer in a p53-dependent manner.

Colorectal cancer (CRC) is considered to be a leading cause of cancer-related death. Centromere protein O (CENPO) can prevent the separation of sister chromatids and cell death after spindle injury. Nevertheless, the role of CENPO in CRC has not been reported. The expression level of CENPO in CRC was revealed by TCGA database and immunohistochemical (IHC) staining. Subsequently, the loss-of-function assays were performed to identified the role of CENPO in CRC in vitro and in vivo. Our data demonstrated that CENPO was highly expressed in CRC. The expression of CENPO was positively correlated with the deterioration of CRC. Moreover, CENPO knockdown inhibited the malignant phenotypes of CRC cells, which was characterized by slowed proliferation, cycle repression at G2, promotion of apoptosis, reduced migration and weakened tumorigenesis. Furthermore, CENPO knockdown downregulated the expression of N-cadherin, Vimentin, Snail, CCND1, PIK3CA and inhibited AKT phosphorylation in CRC cells. Moreover, the function of CENPO in regulating proliferation and apoptosis depended on p53. In summary, CENPO may play a promoting role in CRC through the epithelial mesenchymal transition (EMT) and PI3K/AKT signaling pathway, which can be regarded as a molecular therapeutic target for CRC.

Clinical characteristics and survival analysis of colorectal cancer in China: a retrospective cohort study with 13,328 patients from southern China.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in China. However, detailed clinical characteristics and survival information are limited. This study aimed to investigate the potential epidemiological and clinical risk factors affecting the survival of CRC patients in southern China. METHODS: Patients with primary CRC between 1994 and 2019 at the First and the Sixth Affiliated Hospitals of Sun Yat-sen University (Guangzhou, China) were included. Clinical characteristics and survival outcomes were collected from medical records. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), and Cox's proportional-hazards regression model was used to estimate hazard ratios and 95% confidence intervals. RESULTS: Of all 13,328 patients, 60.1% were men; the mean age was 61.3 years; 53.5% had colon cancer. Among all patients, 1,864 (14.0%) were diagnosed with stage IV disease. The 3- and 5-year OS rates were 79.90% and 71.50%, respectively, whereas the 3- and 5-year PFS rates were 70.30% and 63.90%, respectively. The median OS and PFS times were 189 and 149 months, respectively. Among 13,328 patients, 428 (14.0%) patients with poor/undifferentiated cancer suffered recurrence. In patients with stage III and stage IV diseases, the median PFS times of the patients who received chemotherapy were significantly longer than those in patients who had not received chemotherapy (stage III: 147 vs 62 months, P < 0.001; stage IV: 14 vs 9.5 months, P < 0.001). CONCLUSIONS: This retrospective cohort study illustrates the current status of the clinical characteristics of patients with CRC in southern China. Sex, age, family history, location of cancer occurrence, differentiation status, T status, N status, M status, clinical stage, operation, and surgical margin are independent factors associated with the OS of CRC patients.

Pyroptosis-Mediated Molecular Subtypes and Tumor Microenvironment Infiltration Characterization in Colon Cancer.

The role of pyroptosis, which is also a kind of cell-intrinsic death mechanism, in tumorigenesis and cancer progression has been revolutionized. However, the expression of pyroptosis-related genes (PYGs) in colon cancer (CC) and their prognostic value remain unclear. In this study, we comprehensively identified two PYG-mediated molecular subtypes with a distinct tumor microenvironment (TME) in 1,415 CC samples, which were based on 10 PYGs. The six-gene signature (pyroptosis score, PY-score) was constructed to quantify the molecular patterns of individual tumors using a least absolute shrinkage and selection operator (LASSO)-Cox regression model through the differentially expressed genes between the two molecular subtypes. Significant infiltration of activated immune cells (such as M1 macrophages and cytotoxic T cells) was observed in the low PY-score group, while naive and suppressive immune cells (such as naive CD8+ T cells and M2 macrophages) dominated in the high PY-score group. CC patients in the low PY-score group showed not only significant survival advantage but also sensitivity to immune checkpoint inhibitor treatment, anti-epidermal growth factor receptor (EGFR) therapy, and chemotherapy. Overall, this work revealed that the PYGs played a vital role in the formation of heterogeneity in the TME. The analysis of the PYG-mediated molecular patterns helps in understanding the characterization of TME infiltration and provides insights into more effective therapeutic strategies.

Identification of Candidate Biomarkers and Prognostic Analysis in Colorectal Cancer Liver Metastases.

BACKGROUND: Colorectal cancer (CRC), one of the most common malignant tumors worldwide, has a high mortality rate, especially for patients with CRC liver metastasis (CLM). However, CLM pathogenesis remains unclear. METHODS: We integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in CLM. GEO2R, DAVID 6.8, ImageGP, STRING, UALCAN, ONCOMINE, THE HUMAN PROTEIN ATLAS, GEPIA 2.0, cBioPortal, TIMER 2.0, DRUGSURV, CRN, GSEA 4.0.3, FUNRICH 3.1.3 and R 4.0.3 were utilized in this study. RESULTS: Sixty-three pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened from three gene expression profiles (GSE6988, GSE14297 and GSE81558). Thirty-one up-regulated genes and four down-regulated genes were identified from these three gene expression profiles and verified by another gene expression profiles (GSE 49355) and TCGA database. Two pathways (IGFBP-IGF signaling pathway and complement-coagulation cascade), eighteen key differentially expressed genes (DEGs), six hub genes (SPARCL1, CDH2, CP, HP, TF and SERPINA5) and two biomarkers (CDH2 and SPARCL1) with significantly prognostic values were screened by multi-omics data analysis and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: In this study, we identified a robust set of potential candidate biomarkers in CLM, which would provide potential value for early diagnosis and prognosis, and would promote molecular targeting therapy for CRC and CLM.

HSPA4 Knockdown Retarded Progression and Development of Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is a common malignancy associated with high morbidity and mortality. Heat shock 70 kDa protein 4 (HSPA4) has been shown to exert regulatory roles during tumor progression in different cancer types. Here, we investigated the expression and cellular functions of HSPA4 in CRC. MATERIALS AND METHODS: Expression of HSPA4 in CRC tissues and paracancerous tissues was analyzed by RT-qPCR and immunohistochemistry IHC staining. The functional roles of HSPA4 were explored using shRNA-mediated knockdown in HCT116 and RKO CRC cell lines, both in vitro and in tumor xenograft studies. RESULTS: HSPA4 expression was significantly increased at the RNA and protein levels in CRC tissues compared with noncancerous tissues. Moreover, HSPA4 expression was positively associated with tumor stage and its high expression of HSPA4 indicated poor patient prognosis. In vitro studies established that HSPA4 knockdown inhibited proliferation and migration, causing arrest in the G2-phase of the cell cycle along with increased levels of apoptosis. This phenotype was recapitulated in vivo where HSPA4 knockdown suppressed xenograft growth. Mechanistic investigations showed silencing of HSPA4 reduced activation of the PI3K, Akt signaling axis while also downregulating the cell cycle progression markers, CCND1 and CDK6. Similarly, there was altered expression of apoptosis-related proteins consistent with the increase in apoptosis. CONCLUSION: Our findings demonstrate clinical significance for HSPA4 in CRC, further showing that HSPA4 contributes to CRC tumorigenesis through effects on proliferation, migration and survival. Thus, HSPA4 represents a novel prognostic indicator as well as a promising therapeutic target in CRC.

Association of Preoperative Serum Carcinoembryonic Antigen and Gastric Cancer Recurrence: A Large Cohort Study.

Background and Aim: Measuring postoperative carcinoembryonic antigen (CEA) is recommended by guidelines to help detecting recurrence of gastric cancer patients. However, the prognostic significance of elevated preoperative CEA is unclear. This study aims to investigate whether patients with elevated preoperative CEA have a higher risk of recurrence than patients with normal preoperative CEA. Methods: We conducted a retrospective cohort study at a gastric cancer center in South China. Consecutive patients with stage I to III gastric adenocarcinoma who underwent curative resection at the center from January 2001 to February 2016 were identified. Patients were grouped into two cohorts: normal preoperative CEA (≤ 5 ng/ml), and elevated preoperative CEA (> 5 ng/ml). 3-year recurrence-free survival (RFS) and hazard function curves over time were estimated. Results: A total of 1,596 patients (1,063 {66.6%} male; median {Interquartile range, IQR} age, 59 {50-66} years) were identified. Patients with elevated preoperative CEA had 15.5% lower 3-year RFS (n=222 {70.4%}) than the cohorts with normal preoperative CEA (n=1,374 {85.9%}). The hazard function of recurrence for the two cohorts peaked at the similar time (around 10 months after surgery). Multivariate Cox analyses confirmed that elevated preoperative CEA was independently associated with shorter RFS (Hazard Ratio {HR}, 1.69; 95% confidence interval {CI}, 1.26-2.27; P = 0.001). Conclusions: Patients with elevated preoperative CEA are at increased risk for recurrence, especially within the first 24 months after surgery.

Extensive Dissection at No. 12 Station During D2 Lymphadenectomy Improves Survival for Advanced Lower-Third Gastric Cancer: A Retrospective Study From a Single Center in Southern China.

BACKGROUND: D2 lymphadenectomy including No. 12a dissection has been accepted as a standard surgical management of advanced lower-third gastric cancer (GC). The necessity of extensive No. 12 nodes (No. 12a, 12b, and 12p) dissection remains controversial. This study aims to explore its impact on long-term survival for resectable GC. METHODS: From 2009 to 2016, 353 advanced lower-third GC patients undergoing at least D2 lymphadenectomy during a radical surgery were included, with 179 patients receiving No. 12a, 12b, and 12p dissection as study group. A total of 174 patients with No. 12a dissection were employed as control group. Surgical and long-term outcomes including 90-day complications incidence, therapeutic value index (TVI), 3-year progression-free survival (PFS), and 5-year overall survival (OS) were compared between both groups. RESULTS: No. 12 lymph node metastasis was observed in 20 (5.7%) patients, with 10 cases in each group (5.6% vs. 5.7%, p = 0.948). The metastatic rates at No. 12a, 12b, and 12p were 5.7%, 2.2%, and 1.7%, respectively. The incidence of 90-day complications was identical between both groups. Extensive No. 12 dissection was associated with increased TVI at No. 12 station (3.9 vs. 0.6), prolonged 3-year PFS rate (67.0% vs. 55.9%, p = 0.045) and 5-year OS rate (66.2% vs. 54.0%, p = 0.027). The further Cox-regression analysis showed that the 12abp dissection was an independent prognostic factor of improved survival (p = 0.026). CONCLUSION: Adding No. 12b and 12p lymph nodes to D2 lymphadenectomy might be effective in surgical treatment of advanced lower-third GC and improve oncological outcomes compared with No. 12a-based D2 lymphadenectomy.

A precise temperature control during hyperthermic intraperitoneal chemotherapy promises an early return of bowel function.

INTRODUCTION: The hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely applied in clinical practice for peritoneal carcinomatosis (PC). The temperature is one of the important elements affecting the efficacy of HIPEC, and it can become fluctuant by several factors. This study is aimed to explore the role of a stable perfusion temperature in promoting bowel recovery of PC patients due to gastrointestinal malignancies. METHODS: Between January 2012 and July 2013, 59 PC patients undergoing cytoreductive surgery and three-cycle HIPEC were included. Patients having stable perfusion temperature for all cycles were assigned into the study group, with the rest having unstable temperature into the control group. Time of flatus and defecation passage and initiation time of enteral nutrition were compared between both groups to detect the significance in bowel function recovery, with visual analogue scale (VAS) pain intensity and overall survival (OS) compared meanwhile. RESULTS: In sum, 33 (55.9%) patients obtained stable temperature during HIPEC, and the rest of 26 (44.1%) developed fluctuant perfusion temperature. Average time of flatus (2.3 ± 1.2 vs 3.9 ± 2.2 days, P =.002), defecation passage (5.2 ± 2.1 vs 7.1 ± 2.9 days, P =.004) and enteral nutrition initiation (4.3 ± 1.5 vs 6.7 ± 2.3 days, P <.001) were much shorter in the study group than the control group. Additionally, the VAS score (4.5 ± 2.3 vs 6.3 ± 1.3, P <.001) and 5-year OS rate (17.8% vs 11.1%, P=.135) were both improved, with significance observed in postoperative pain control. CONCLUSIONS: During HIPEC, a precise temperature control could promise an early recovery of bowel function and reduce postoperative pain, without survival significance found based on the current cohort.

Gastric cancer in young patients: a separate entity with aggressive features and poor prognosis.

PURPOSE: To investigate the clinicopathological features and survival outcomes between young and old patients with gastric cancer (GC), and further determine the role of young age in the prognosis of GC. METHODS: Patients with stage I-III gastric adenocarcinomas undergoing curative surgery were enrolled, divided into young (aged 18-49 years, YG), middle-aged (50-59 years, MG), and old (≥ 60 years, OG) groups. Exclusion criteria were neoadjuvant therapy and history of malignant tumors. Clinicopathological features, overall survival (OS), disease-free survival (DFS), and recurrence patterns were compared among three groups. RESULTS: 1131 patients were finally included, with 270, 314, and 547 cases in the YG, MG, and OG, respectively. Compared to others, YG had higher proportion of female, middle-third gastric cancer, poor differentiation, N3b stage, and adjuvant chemotherapy. YG demonstrated poorer 5-year OS than MG (62.4% vs. 70.8%, P = 0.019), but better than OG (62.4% vs. 58.7%, P = 0.031). YG also suffered inferior 5-year DFS (75.2% vs. 82.8%, P = 0.040) compared with MG, and higher incidence of peritoneal recurrence than MG (15.1% vs. 5.2%, P < 0.001) and OG (15.1% vs. 4.1%, P < 0.001). Multivariate analysis identified young age as the independent prognostic factor for OS [hazard ratio (HR) = 1.347, 95% CI 1.018-1.781, P = 0.037], DFS (HR = 1.601, 95% CI 1.079-2.376, P = 0.019), and peritoneal recurrence (HR = 2.936, 95% CI 1.505-5.726, P = 0.002). CONCLUSIONS: Young GC patients demonstrated aggressive features with poor prognosis and enhanced management may be warranted for this subgroup.

The impacts of the number of prefreeze and postthaw blastomeres on embryo implantation potential: A systematic analysis.

To systematically analyze the potential of embryo implantation through comparison between the number of surviving blastomeres, the growth, and implantation rate.Retrospective analysis on implantation rate and the growth of prefreeze-postthaw embryos with different blastomeres in 1487 frozen embryo transfer cycles.In groups of postthaw embryos without damage, implantation rate and the average number of blastomere growth increased significantly with increasing number of blastomeres. The implantation rate and the number of blastomeres of embryos with 8-8c (the number of blastomeres in prefreeze embryo-the number of blastomeres in postthaw embryo) continued to grow at a significantly higher rate than that of 5-5c and 6-6c (P < .05). In groups of embryos with the same number of blastomeres before freezing and with partial damage after resuscitation, the implantation rates were lower and the average numbers of blastomere growth reduced as the number of damaged blastomeres increased. For embryos with good quality before freezing, 1 to 3 damaged blastomeres in postthawed embryos did not affect the development and implantation rate. Both implantation rate and growth rate of embryos with 8-6c were significantly higher than those of embryos with 6-6c (P < .05).The number of surviving blastomeres and growth in frozen-thawed embryos could be important index to predict embryo development potential and clinical outcome of implantation. For embryos with good quality, a small amount of damaged blastomeres would not weaken embryo development potential and implantation rate after being thawed.

Ultra pH-sensitive polymeric nanovesicles co-deliver doxorubicin and navitoclax for synergetic therapy of endometrial carcinoma.

Endometrial carcinoma is a kind of epithelial malignant tumor occurring in the endometrium with high incidence (nearly 200 000 people are diagnosed every year). At present, surgery is the main strategy for the treatment of endometrial carcinoma. However, in special cases such as serous, clear cell carcinoma and postoperative recurrences, chemotherapy is still essential and indispensable. The combined chemotherapy schemes of cisplatin, paclitaxel and doxorubicin (DOX) in clinical applications are unfortunately complicated and easily cause severe side effects. In recent years, with the development of nanotechnology, the targeted delivery of multi-chemotherapeutic drugs shows great advantages in reducing side effects and improving anticancer efficacy. Here, an ultra pH-sensitive nanovesicle based on polyethylene glycol-poly(diisopropylamino)ethyl methacrylate (PEG-PDPA) was fabricated. A chemotherapeutic drug (doxorubicin) and an anti-apoptotic Bcl-2 inhibitor (navitoclax) were co-encapsulated in the hydrophilic cavity and hydrophobic membrane of the vesicle, respectively. After accumulating in the tumor tissue via the enhanced permeability and retention (EPR) effect, the nanovesicles could be efficiently diffused in tumor cells by endocytosis and then rapidly release drugs in response to the lysosomal acidic environment, leading to an enhanced tumor-killing effect based on the combination therapy between DOX and the Bcl-2 inhibitor. The drug co-delivery system and microenvironment-triggered drug release may provide an efficient strategy for endometrial carcinoma therapy.

ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer.

The Serine-Glycine-One-Carbon (SGOC) pathway is pivotal in multiple anabolic processes. Expression levels of SGOC genes are deregulated under tumorigenic conditions, suggesting participation of oncogenes in deregulating the SGOC biosynthetic pathway. However, the underlying mechanism remains elusive. Here, we identified that Interleukin enhancer-binding factor 3 (ILF3) is overexpressed in primary CRC patient specimens and correlates with poor prognosis. ILF3 is critical in regulating the SGOC pathway by directly regulating the mRNA stability of SGOC genes, thereby increasing SGOC genes expression and facilitating tumor growth. Mechanistic studies showed that the EGF-MEK-ERK pathway mediates ILF3 phosphorylation, which hinders E3 ligase speckle-type POZ protein (SPOP)-mediated poly-ubiquitination and degradation of ILF3. Significantly, combination of SGOC inhibitor and the anti-EGFR monoclonal antibody cetuximab can hinder the growth of patient-derived xenografts that sustain high ERK-ILF3 levels. Taken together, deregulation of ILF3 via the EGF-ERK signaling plays an important role in systemic serine metabolic reprogramming and confers a predilection toward CRC development. Our findings indicate that clinical evaluation of SGOC inhibitor is warranted for CRC patients with ILF3 overexpression.

Gastric duplication 20 years after a partial distal gastrectomy: a case report and review of literature.

Gastric duplications are the least common gastrointestinal duplications, especially in adults. Duplication cyst with an accessory pancreatic lobe is extremely rare and is even more uncommon in the setting of polysplenia. No gastric duplication after partial gastrectomy has been reported. We present a 41-year-old male diagnosed with gastric duplications with an accessory pancreatic lobe and polysplenia. Another characteristic of this case is partial gastrectomy 20 years ago without the discovery of duplication cysts. The gastric duplications, accessory pancreatic lobe and accessory spleen were successfully resected.

Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation.

Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear. Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation. Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection. Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5'UTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation. Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.

Detection of T lymphocyte subsets and related functional molecules in follicular fluid of patients with polycystic ovary syndrome.

Immune responses play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the characteristics of T lymphocyte subsets in PCOS remain insufficiently understood. In this study, lymphocytes of follicular fluid (FF) were obtained from oocyte retrieval before in-vitro fertilization (IVF) in infertile women with or without PCOS. The levels of cluster of differentiation 25 (CD25), CD69, programmed death 1 (PD-1), interferon-γ (IFN-γ), interleukin 17A (IL-17A) and IL-10 in T lymphocytes were determined by flow cytometry. Our results showed that the percentage of FF CD8+ T cells was significantly decreased in infertile patients with PCOS (P < 0.05). Furthermore, the levels of CD69 and IFN-γ were significantly decreased and the level of PD-1 was increased in both CD4+ and CD8+ T cells from infertile patients with PCOS (P < 0.05). Moreover, the expression of PD-1 on CD4+ or CD8+ T cells was positively correlated with the estradiol (E2) levels in the serum and reversely correlated with the expression of IFN-γ in CD4+ or CD8+ T cells in infertile patients with PCOS. These results suggested that T cell dysfunction may be involved in the pathogenesis of PCOS.

Distinct Prognosis of High Versus Mid/Low Rectal Cancer: a Propensity Score-Matched Cohort Study.

BACKGROUND: Rectal cancers have long been treated as a single-entity disease; however, whether the prognosis of high rectal cancer (inferior margin located 10.1 to 15.0 cm from the anal verge) differs from that of mid/low rectal cancer (0 to 10.0 cm) remains disputed. METHODS: Patients with stages I-III rectal adenocarcinomas undergoing curative-intent surgery were enrolled between 2007 and 2013 in this retrospective analysis. Exclusion criteria were neoadjuvant therapy or concurrent cancers. Propensity score matching and Cox regression analysis were performed to compare a 5-year overall and cancer-specific survival between patients with high and mid/low rectal cancer. RESULTS: Of 613 patients who met the inclusion criteria, 199 (32.5%) and 414 (67.5%) had high and mid/low rectal cancer, respectively. After propensity score matching (187 cases for each group), the high group showed a better overall survival (70.9 vs. 56.9%, p = 0.042) and cancer-specific survival (77.4 vs. 60.3%, p = 0.028) at 5 years compared with the mid/low group with stage III disease. However, high rectal cancer did not demonstrate prognostic superiority in stages I-II disease. Multivariate analysis identified high tumor location as an independent prognostic factor for cancer-specific survival (hazards ratio = 0.422, 95% confidence interval 0.226-0.786, p = 0.007) and overall survival (hazards ratio = 0.613, 95% confidence interval 0.379-0.991, p = 0.046). CONCLUSIONS: Patients with stage III high rectal adenocarcinoma demonstrated better overall and cancer-specific survival than those with mid/low type, and tumor location was an independent prognostic factor for patients with rectal carcinomas.

Nephrotoxicity and long-term survival investigations for patients with peritoneal carcinomatosis using hyperthermic intraperitoneal chemotherapy with cisplatin: A retrospective cohort study.

BACKGROUND & PURPOSE: Cytoreductive surgery (CRS) plus Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for peritoneal carcinomatosis. The cisplatin (CP) applied in HIPEC carries a risk of kidney injury. This study aims to investigate CP-induced nephrotoxicity post HIPEC and to explore its risk factors. METHODS: From January 2012 to July 2013, 99 patients undergoing CRS + HIPEC were retrospectively reviewed. Patients were divided into CP and Non-CP HIPEC groups. The RIFLE classification was used to assess the severity of acute kidney injury (AKI). Renal and hepatic function, concentrations of tumor markers, and postoperative outcomes were compared between groups. RESULTS: 47 (47.5%) patients were in the CP HIPEC group, with 52 (52.5%) patients in the Non-CP HIPEC group. 11 (11.1%) patients developed AKI, with 10 of them from the CP HIPEC group. Two patients with CP-contained HIPEC developed acute renal failure. Plasma levels of both urea nitrogen and creatinine were significantly increased in the CP HIPEC group compared with the Non-CP HIPEC group (P < 0.01). However, postoperative pain (scaled score, 4.2 vs. 3.8; P = 0.279), length of hospital stay (18.1 vs. 20.2 days; P = 0.285), hospital costs ($1 3182 vs. $12 640; P = 0.465) and incidence of postoperative complication (25.5% vs. 17.3%; P = 0.337) were similar in both groups, with comparable 3-year overall survival observed (38.6% vs. 31.8%, P = 0.319). A multivariate analysis indicated that use of CP was an independent risk factor for AKI (P = 0.017, 95% CI: 1.277-4.155). CONCLUSIONS: Application of CP during HIPEC is associated with an increased risk of nephrotoxicity, without promising long-term survival benefit.