Development and validation of a nomogram for predicting metachronous peritoneal metastasis in colorectal cancer: A retrospective study.

BACKGROUND: Peritoneal metastasis (PM) after primary surgery for colorectal cancer (CRC) has the worst prognosis. Prediction and early detection of metachronous PM (m-PM) have an important role in improving postoperative prognosis of CRC. However, commonly used imaging methods have limited sensitivity to detect PM early. We aimed to establish a nomogram model to evaluate the individual probability of m-PM to facilitate early interventions for high-risk patients. AIM: To establish and validate a nomogram model for predicting the occurrence of m-PM in CRC within 3 years after surgery. METHODS: We used the clinical data of 878 patients at the Second Hospital of Jilin University, between January 1, 2014 and January 31, 2019. The patients were randomly divided into training and validation cohorts at a ratio of 2:1. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the variables with nonzero coefficients to predict the risk of m-PM. Multivariate logistic regression was used to verify the selected variables and to develop the predictive nomogram model. Harrell's concordance index, receiver operating characteristic curve, Brier score, and decision curve analysis (DCA) were used to evaluate discrimination, distinctiveness, validity, and clinical utility of this nomogram model. The model was verified internally using bootstrapping method and verified externally using validation cohort. RESULTS: LASSO regression analysis identified six potential risk factors with nonzero coefficients. Multivariate logistic regression confirmed the risk factors to be independent. Based on the results of two regression analyses, a nomogram model was established. The nomogram included six predictors: Tumor site, histological type, pathological T stage, carbohydrate antigen 125, v-raf murine sarcoma viral oncogene homolog B mutation and microsatellite instability status. The model achieved good predictive accuracy on both the training and validation datasets. The C-index, area under the curve, and Brier scores were 0.796, 0.796 [95% confidence interval (CI) 0.735-0.856], and 0.081 for the training cohort and 0.782, 0.782 (95%CI 0.690-0.874), and 0.089 for the validation cohort, respectively. DCA showed that when the threshold probability was between 0.01 and 0.90, using this model to predict m-PM achieved a net clinical benefit. CONCLUSION: We have established and validated a nomogram model to predict m-PM in patients undergoing curative surgery, which shows good discrimination and high accuracy.

Prognostic significance of CD56 antigen in newly diagnosed multiple myeloma: A real-world retrospective study.

The prognostic value of plasma cell CD56 expression of patients with multiple myeloma (MM) has been reported in many studies, but the results are controversial. This study aimed to examine the prognostic significance of CD56 in MM patients. Eighty seven patients with newly diagnosed MM were enrolled in this study, and their clinical characteristics, immunophenotypes, and cytogenetics were retrospectively analyzed to explore the prognostic significance of CD56 expression. Multiparameter flow cytometry was used to detect MM in bone marrow samples from all patients. Patients were divided into 2 groups based on whether they expressed CD56: CD56 + group and CD56 - group. After 4 cycles of chemotherapy, the overall response rate of the CD56 - patients was lower than that of the CD56 + patients (60.0% vs 81.1%, P = .036). Survival analysis showed that the median progression-free survival (PFS) was 10 months for the CD56 - group and 27 months for the CD56 + group (P = .007). The median overall survival (OS) of patients for the CD56 - group was 25 months versus not reached in the CD56 + group (P = .010). In addition, among the high-risk patients detected by fluorescence in situ hybridization (FISH), the median PFS was 4 months for the CD56 - group and 16 months for the CD56 + group (P = .012). The median OS of the CD56 + group and CD56 - group was 36 months and 15 months, respectively, with statistically significant differences (P = .017). Our study confirmed that CD56 - patients with MM had a worse prognosis than that of CD56 + patients with MM. Among the patients with ≥ 2 high-risk cytogenetics, the existence of the CD56 negativity can further identify MM patients with poor PFS and OS.

Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure-induced hypertension in rats.

Background: Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure-induced hypertension (CIH) and identify the underlying mechanisms in SD rats. Methods: One group of rats was housed at room temperature and served as control. Three groups of rats were kept in a 4°C cold incubator for 10 h/day; among which two groups were administrated with either benzamil (EnNaC blocker) or eplerenone (mineralocorticoid receptor antagonist, MR). Blood pressure (BP), vasodilatation, and endothelial function were measured with tail-cuff plethysmography, isometric myograph, and Total Nitric Oxide (NO) Assay kit, respectively. A cell-attached patch-clamp technique, in split-open MA, was used to determine the role of EnNaC in CIH rats. Furthermore, the plasma aldosterone levels were detected using an ELISA kit; and Western blot analysis was used to examine the relative expression levels of Sgk1 and Nedd4-2 proteins in the MA of SD rats. Results: We demonstrated that cold exposure increased BP, impaired vasodilatation, and caused endothelial dysfunction in rats. The activity of EnNaC significantly increased, concomitant with an increased level of plasma aldosterone and activation of Sgk1/Nedd4-2 signaling. Importantly, CIH was inhibited by either eplerenone or benzamil. It appeared that cold-induced decrease in NO production and impairment of endothelium-dependent relaxation (EDR) were significantly ameliorated by either eplerenone or benzamil in MA of CIH rats. Moreover, treatment of MAs with aldosterone resulted in an activation of EnNaC, a reduction of NO, and an impairment of EDR, which were significantly inhibited by either eplerenone or GSK650394 (Sgk1 inhibitor) or benzamil. Conclusion: Activation of EnNaC contributes to CIH; we suggest that pharmacological inhibition of the MR/Sgk1/Nedd4-2/EnNaC axis may be a potential therapeutic strategy for CIH.

Efficacy of staple line reinforcement by barbed suture for preventing anastomotic leakage in laparoscopic rectal cancer surgery.

BACKGROUND: Anastomotic leakage (AL) is a severe complication in rectal cancer surgery. Various methods, including intracorporeal reinforcing suturing, have been used to reduce the incidence of AL. However, little is known about the efficacy of staple-line reinforcement by barbed suture for preventing AL. AIM: To evaluate the efficacy of staple-line reinforcement using barbed suture for preventing AL in laparoscopic surgery for rectal cancer. METHODS: We retrospectively reviewed the clinical datum of 319 patients undergoing laparoscopic low anterior resection combined with double stapling technique between May 1, 2017 and January 31, 2021. All surgeries were performed by the same surgical team specializing in colorectal surgery. Patients were divided into two groups depending on whether they received reinforcing sutures. Patients' baseline characteristics did not show any significant difference between the two groups. We analyzed patient-, tumor-, as well as surgery-related variables using univariate and multivariate logistic analyses. RESULTS: There were 168 patients in the reinforcing suture group and 151 patients in the non-reinforcing suture group. AL occurred in 25 cases (7.8%). Its incidence was significantly higher in the non-reinforcing suture group than in the reinforcing suture group (4.8% vs 11.3%, P = 0.031). The multivariate analyses demonstrated that the tumor site, tumor size and presence of staple-line reinforcement were independent risk factors for AL. We divided these patients into two risk groups based on the combination of tumor site and tumor size. Patients without any risk factor were assigned to the low-risk group (n = 177), whereas those having one or two risk factors were assigned to the high-risk group (n = 142). In the high-risk group, the AL incidence considerably decreased in the reinforcing suture group compared with that in the non-reinforcing suture group (P = 0.038). Nonetheless, no significant difference was found in the low-risk group between the two groups. CONCLUSION: Staple-line reinforcement by barbed suture may decrease the incidence of AL. A large-scale prospective randomized controlled trial is needed for evaluating the efficacy of staple-line reinforcement for preventing AL.

Transperineal pelvic drainage combined with lateral position to promote perineal wound healing after abdominoperineal resection: A prospective cohort trial.

BACKGROUND: For the rectal cancer <5 cm from anal margin, extralevator abdominoperineal resection (eAPR) has been accepted widely by surgeons. However, the rate of perineal infection following up eAPR is approximately 70%. We did the study with the aim of evaluating the effect and safety of transperineal pelvic drainage combined with lateral position (TPDLP) on perineal wound in patients undergoing eAPR. METHODS: Patients were randomly assigned to N-TPDLP group (standard arm) or TPDLP group (intervention arm). In the standard arm, surgery was completed after abdominal drainage tube was placed in pelvic. Comparatively, an additional transperineal wound drainage tube was applied in the experimental arm. Postoperatively, patients of both 2 groups were informed not to sit to reduce perineal compression until the perineal wound healed. But lateral position was demanded in the intervention arm. The primary endpoint was the rate of uncomplicated perineal wound healing defined as a Southampton wound score of <2 at 30 days postoperatively. Patients were followed for 6 months. RESULTS: In total, 60 patients were randomly assigned to standard arm (n = 31) and intervention arm (n = 29). The mean perineal wound healing time was 34.2 (standard deviation [SD] 10.9) days in TPDLP arm, which significantly differ from 56.4 (SD 34.1) in N-TPDLP arm (P = .001). At 30 days postoperatively, 3 (10%) of 29 patients undergoing TPDLP were classified into grade 4 according to Southampton wound score, however, 16 (52%) of 31 patients were classified into grade 4 in control arm, and significantly difference was observed between randomization groups (P = .001). What's more, perineal wound pain was assessed at 30 days postoperatively, and it is discovered that the pain degree of patients in control arm was significantly more severe than the interventive arm (P = .015). CONCLUSION: In the present study, we found that TPDLP generated a favorable prognosis for perineal wounds with acceptable side-effects.

Multidimensional Analysis of CHMP Family Members in Hepatocellular Carcinoma.

Background: EGFR frequently accumulates and mutates simultaneously in various cancers. Ubiquitinated EGFR proteins can be degraded by the endosomal sorting complex required for transport. Among them, ESCRTIII is mainly composed of CHMP family members. Methods: A total of 424 samples from the TCGA-LIHC data set were used to explore the relationship between CHMPs and liver hepatocellular carcinoma (LIHC). Oncomine, the Human Protein Altas, cBioPortal, TISIDB, TIMER, Metascape, and R software were used to facilitate analysis of the role played by CHMPs in the pathogenesis of LIHC. The role of CHMPs in the development of LIHC was analyzed in terms of differential expression, survival, mutation, immunoinfiltration, functional enrichment, and drug sensitivity. Results: Differential expression analysis showed that CHMPs were significantly more expressed in LIHC tumor tissue, and the high expression of some CHMPs was closely correlated with clinicopathological stage. The prognosis was worse in the group with high expression of CHMPs. Among them, CHMP4C was considered to play a major role. Gene-mutation analysis and DNA promoter-methylation analysis further revealed possible mechanisms for the aberrant amplification of CHMPs. Immunoinfiltration analysis indicated that CHMPs were closely associated with multiple immune cells and exhibited resistance to various drugs when highly expressed. Conclusion: CHMPs were found to be significantly elevated in LIHC and strongly associated with immune-cell infiltration, poor prognosis, multiple star pathways, and drug resistance.

Botulinum Toxin Injections for Treatment of Drooling in Children with Cerebral Palsy: A Systematic Review and Meta-Analysis.

BACKGROUND: We aimed to review and analyse the effectiveness and safety of botulinum toxin type A (BoNT-A) injections for drooling in children with cerebral palsy. DATA SOURCES: We searched the EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) databases from inception to January 2020. METHODS: We included randomized controlled trials and observational studies which (1) involved children with cerebral palsy, (2) used BoNT-A for control of drooling, and (3) provided quantitative evaluations of drooling before and after intervention with BoNT-A. RESULTS: Twenty-one trials met the inclusion criteria. Most studies showed that BoNT-A injections are safe and efficacious as a treatment for drooling in children with cerebral palsy. Four trials had sufficient data to pool the results for the meta-analysis. Both the drooling quotient (p = 0.002) and drooling Ffrequency and severity scale (p = 0.004) supported this conclusion. CONCLUSION: BoNT-A injections are a safe, reversible, effective treatment for drooling control in children with cerebral palsy that can offer effectiveness for more than 3 months with few side effects. The dosage of BoNT-A should not exceed 4 units/kg. Further studies are required to determine the optimal dosage and target glands.

Diagnostic Value of sIL-2R, TNF-α and PCT for Sepsis Infection in Patients With Closed Abdominal Injury Complicated With Severe Multiple Abdominal Injuries.

Objective: We aimed to evaluate the diagnostic value of soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), and combined detection for sepsis infection in patients with closed abdominal injury complicated with severe multiple abdominal injuries. Patients and Methods: One hundred forty patients with closed abdominal injury complicated with severe multiple abdominal injuries who were diagnosed and treated from 2015 to 2020 were divided into a sepsis group (n = 70) and an infection group (n = 70). Results: The levels of sIL-2R, TNF-α, and PCT in the sepsis group were higher than those in the infection group (p < 0.05). The receiver operating characteristic (ROC) curve showed that the areas under the ROC curve (AUCs) of sIL-2R, TNF-α, PCT and sIL-2R+TNF-a+PCT were 0.827, 0.781, 0.821, and 0.846, respectively, which were higher than those of white blood cells (WBC, 0.712), C-reactive protein (CRP, 0.766), serum amyloid A (SAA, 0.666), and IL-6 (0.735). The AUC of the three combined tests was higher than that of TNF-α, and the difference was statistically significant (p < 0.05). There was no significant difference in the AUCs of sIL-2R and TNF-α, sIL-2R and PCT, TNF-α and PCT, the three combined tests and sIL-2R, and the three combined tests and PCT (p > 0.05). When the median was used as the cut point, the corrected sIL-2R, TNF-α, and PCT of the high-level group were not better than those of the low-level group (p > 0.05). When the four groups were classified by using quantile as the cut point, the OR risk values of high levels of TNF-α and PCT (Q4) and the low level of PCT (Q1) after correction were 7.991 and 21.76, respectively, with statistical significance (p < 0.05). Conclusions: The detection of sIL-2R, TNF-α, and PCT has good value in the diagnosis of sepsis infection in patients with closed abdominal injury complicated with severe multiple abdominal injuries. The high concentrations of PCT and TNF-α can be used as predictors of the risk of septic infection.

Skeletal muscle metastasis with bone metaplasia from colon cancer: A case report and review of the literature.

BACKGROUND: Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon. Lymphatic and hematogenous metastases occur frequently in colon cancer and the most common metastatic sites include the liver, lung, peritoneum, bone, and lymph nodes. As a manifestation of advanced tumor spread and metastasis, soft tissue metastasis, especially skeletal muscle metastasis with bone metaplasia caused by colon cancer, is rare, accounting for less than 1% of metastases. CASE SUMMARY: A 43-year-old male patient developed skeletal muscle metastasis with bone metaplasia of the right proximal thigh 5 mo after colon cancer was diagnosed. The patient was admitted to the hospital because of pain caused by a local mass on his right thigh. Positron emission tomography-computed tomography showed many enlarged lymph nodes around the abdominal aorta but no signs of lung or liver metastases. Color ultrasound revealed a mass located in the skeletal muscle and the results of histological biopsy revealed a poorly differentiated adenocarcinoma suspected to be distant metastases from colon cancer. Immunohistochemistry showed small woven bone components that were considered to be ossified. CONCLUSION: This case reminds us that for patients with advanced colorectal tumors, we should be alert to the possibility of unconventional metastasis.

Twisted light induced magnetic anisotropy changes in an interlayer exchange coupling system.

All-optical switching of magnetic materials is a potential method for realizing high-efficiency and high-speed data writing in spintronics devices. The current method, which utilizes two circular helicities of light to manipulate magnetic domains, is based on femtosecond pulsed lasers. In this study, we demonstrate a new all-optical switching method using a continuous-wave Laguerre-Gaussian beam (twisted light), which allows photons to carry orbital angular momentum with discrete levels, lℏ, to modify the magnetic anisotropy of an interlayer exchange coupling system. The easy axis of the heterojunction Pt(5 nm)/Co(1.2 nm)/Ru(1.4 nm)/Co(0.4 nm)/Pt(5 nm) on a SiO2/Si substrate dramatically changed after illuminating it with a laser beam carrying a sufficient quantum number of orbital angular momentum. Based on a simple numerical calculation, we deduced that the interaction between the dynamical phase rotation of the electric field and the metal surface could generate an in-plane circular current loop that consequently induces a perpendicular stray field to change the magnetic anisotropy. This finding paves the way for developments in the field of magnetic-based spintronics using light with orbital angular momentum.

Effect and safety of intraoperative intraperitoneal chemotherapy on patients suffering from colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), the third most commonly diagnosed malignant carcinoma and the third most common cause of carcinoma-related mortality, continues to be a major international health problem. And approximately 33% of patients suffer from recurrence after radical surgery. Free malignant cell implanting in the peritoneum is generally accepted as one of the main reasons of such outcome. We did this present clinical study with the aim of evaluating the effects and safety of intraoperative intraperitoneal chemotherapy (IOC) on patients suffering from colorectal cancer, with hoping to find a novel, effective, and available approach to deal with malignant cell implanting during surgeries. METHODS: In total, 391 patients who went through colorectal radical surgery were considered eligible between June 1, 2017, and December 31, 2018. 220 patients were treated with surgery without IOC, while other 171 patients received surgery plus IOC. Clinical characteristics, operative findings, postoperative short-term outcomes, disease-free survival (DFS), and overall survival (OS) were compared between these above 2 groups in the selected population. RESULT: The present research included 391 patients (251 men and 140 women) who underwent surgery without IOC (n = 171) or surgery plus IOC (n = 220), with a mean (SD) age of 60.4 (9.7) years in the surgery without IOC group and 60.6 (8.7) in the surgery plus IOC group (P=.85). No significant differences were witnessed between the two groups in surgery-related information and postoperative complications. It is worth noting that IOC independent of other factors was associated with a favor prognosis in CRC patients with stage II/III (HR 0.50, 95%CI 0.30-0.82, P=.006). Moreover, for patients with stage II colorectal carcinoma, DFS did not differ between two groups (P=.553, Kaplan-Meier log-rank), and OS was no exception. In stage III CRC patients, the estimated DFS rate for patients receiving IOC was 82.2% and patients without IOC was 66.4% after 3 years, which demonstrated that IOC was associated with a favorable prognosis in stage III patients (P=.012, Kaplan-Meier log-rank). Furthermore, the differences were still remained between the two groups when considering the influence about postoperative chemotherapy (P=.014, Kaplan-Meier log-rank). IOC can also significantly improve patients' overall survival whether they get treatment with POC (P=.006, Kaplan-Meier log-rank; P=.025, Kaplan-Meier log-rank). CONCLUSIONS: In the present study, we have found that surgery plus IOC generated a favorable prognosis for stage III CRC patients but not stage II without any side-effects when the dosage of lobaplatin was 0.1g/L. As a new, safe, and simple procedure, IOC therapy is easily performed-and does not require any special devices or techniques. Thus, IOC is a promising and exciting therapeutic strategy for patients with CRC.

[Diagnostic Value of ROC Curve Evaluating Serum Related Indexes for Bloodstream Infection in Patients with Hematopathy].

AbstractObjective: To evaluate the diagnostic value of serum PCT, CRP and SAA for bloodstream infection(BSI) in patients with hematopathy. METHODS: Sixty hematopathy patients with bloodstream infection from July 2016 to June 2018 were selected and enroued in bloodstream infection group. Sixty-five patients with negative blood culture during the same period were selected and enrolled in non-bloodstream infection group. The ROC curves were drawn and used to eualuate the diagnostic value of above montioned indexes. RESULTS: The levels of PCT, CRP and SAA in the bloodstream infection group were higher than those in the non-bloodstream infection group (P<0.05). ROC curve showed that AUC values of PCT, CRP, SAA and the combined test detection were 0.868, 0.746, 0.678 and 0.900, respectively, there was no significant difference in AUC between combined test and PCT test (P>0.05). AUC of combined test and PCT test were higher than those of CRP and SAA test, and the difference was statistically significant (P<0.05), but there was no significant difference in AUC between CRP and SAA (P>0.05). The optimal PCT detection threshold was 0.49 ng/ml, the sensitivity and specificity were 75.0% and 83.1%, respectively. The optimal critical value for CRP detection was 15.76 mg/L, the sensitivity and specificity were 60.0% and 80.0% respectively. The optimal SAA detection threshold was 35.66 mg/L, the sensitivity and specificity were 81.7% and 53.8%, respectively. CONCLUSION: PCT, CRP and SAA detection have good diagnostic value for blood stream infection in patients with hematopathy. The diagnostic value of PCT is better than CRP and SAA, and there is no significant difference in diagnostic value between combined test and PCT test.

Short-term outcomes of laparoscopic intersphincteric resection with intraoperative radiotherapy using low-energy X-rays for primary locally advanced low rectal cancer: a single center experience.

BACKGROUND: Even with the augmentative application of anal-preservation surgery in low rectal cancer, the role and indications of laparoscopic intersphincteric resection (Lap ISR) are still under debate, especially for T3 or node-positive (T3N0M0, T1-3N+M0) cancer, mainly due to the oncological safety and functional outcomes. INTRABEAM (Carl Zeiss, Germany) intraoperative radiotherapy (IORT) using low-energy X-rays features in accurate irradiation, less exposure, and reduced complications. Taking advantages of Lap ISR and INTRABEAM IORT, this innovative approach aims to increase the probability of the anal preservation with acceptable postoperative outcomes. MATERIALS AND METHODS: From December 2015 to August 2019, we retrospectively analyzed the short-term outcomes of 12 patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1-3N+M0) primary locally advanced low rectal cancer. They all had received Lap ISR and INTRABEAM IORT with a dose of 16-18 Gy applied by an applicator through the anus (natural orifice). Then, with no pre- or postoperative radiotherapy given, the patients were suggested to receive 6-8 cycles of the XELOX chemotherapy regimen (oxaliplatin, 130 mg/m2 and capecitabine, 1000 mg/m2). RESULTS: All patients achieved R0 resection. The median radiation time was 27 min and 15 s, and the mean radiative dose was 17.3 Gy (range 16-18 Gy). The median follow-up time was 18.5 months (range 3-45 months). Two patients experienced local recurrence. Two male patients experienced anastomotic stenosis. Furthermore, one of them experienced perianal abscess and the other one experienced pulmonary metastasis after refusing to receive chemotherapy. One female patient with internal anal sphincter invasion experienced distant metastases to the liver and gluteus maximus muscle 35 months after IORT. No acute radiation injuries or symptoms were observed. Although they experienced a reduction in anal function, every patient was satisfied with the postoperative outcomes. CONCLUSIONS: For patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1-3N+M0) primary locally advanced low rectal cancer, Lap ISR with INTRABEAM IORT may be a safe and feasible approach for anal preservation without compromising oncological outcomes.

Knockdown of long noncoding RNA PVT1 suppresses cell proliferation and invasion of colorectal cancer via upregulation of microRNA-214-3p.

Long noncoding RNAs (lncRNAs) have been reported to be involved in the occurrence and tumorigenesis of numerous malignant cancers. Microarray expression profiles were used to screen colorectal cancer (CRC)-related differentially expressed genes and lncRNAs, which revealed that insulin receptor substrate 1 (IRS1) and lncRNA plasmacytoma variant translocation 1 (PVT1) were highly expressed in CRC. This study aimed to investigate the regulatory role of lncRNA PVT1 in CRC. Subcellular localization detected by fluorescence in situ hybridization identified that lncRNA PVT1 was primarily located in the cytoplasm. The interaction between lncRNA PVT1 and microRNA-214-3p (miR-214-3p) and IRS1 was predicted using the RNA22 website. Next the dual luciferase reporter gene assay, RNA pull-down, and RNA immunoprecipitation assays verified lncRNA PVT1 to be a competitive endogenous RNA (ceRNA) against miR-214-3p, and IRS1 was found to be a target of miR-214-3p. The expression pattern of lncRNA PVT1, miR-214-3p, IRS1, phosphoinositide 3-kinase (PI3K), and Akt was characterized in response to lncRNA PVT1 silencing or miR-214-3p upregulation. Meanwhile, their regulatory effects on cell proliferation, invasion, and apoptosis were detected in CRC cells. With increased levels of miR-214-3p and decreased levels of lncRNA PVT1 in CRC cells, the expression of phosphatidylinositol 3-kinase, putative (PI3K) and Akt was reduced, and consequently, the cell apoptosis was stimulated and cell proliferation and invasion were suppressed. All in all, lncRNA PVT1 competitively binds to miR-214-3p to upregulate the expression of IRS1 thus activating the PI3K/Akt signaling pathway, thus accelerating CRC progression. This study suggests that lncRNA PVT1 might be a potential target of therapeutic strategies for CRC treatment.NEW & NOTEWORTHY This study mainly suggests that long noncoding (lnc)RNA plasmacytoma variant translocation 1 (PVT1) is a downregulated lncRNA in colorectal cancer (CRC), accelerating CRC progression. Strikingly, lncRNA PVT1 acts as a competitive endogenous RNA against microRNA (miR)-214-3p, whereas miR-214-3p targets insulin receptor substrate 1, which draws a comprehensive picture of the potential molecular mechanisms of lncRNA PVT1 in CRC.

The mechanism of miR-16-5p protection on LPS-induced A549 cell injury by targeting CXCR3.

OBJECTIVE: To study the effect of miR-16-5p on lung cancer cell injury and apoptosis, and its mechanism. METHODS: LPS induced lung cancer cell A549 injury; qRT-PCR method was applied to detect the expression of miR-16-5p and CXCR3 in A549 cells. Con (without LPS treatment), LPS + miR-NC group (transfected negative control samples), LPS + miR-16-5p group (transfected miR-16-5p mimics); LPS + si-NC group (transfected negative control samples), LPS + si-CXCR3 group (transfected si-CXCR3); LPS + miR-16-5p + pcDNA3.1 group (co-transfected miR-16-5p mimics and pcDNA3.1), LPS + miR-16-5p + pcDNA3.1-CXCR3 group (co-transfected miR-16-5p mimics and pcDNA3.1-CXCR3) were transfected into A549 cells by liposome method. Western blot was used to detect protein expression of CXCR3, IL-6 and TNF-α in A549 cells; apoptosis of A549 cells was detected by flow cytometry. RESULTS: Compared with the control group, the expression of miR-16-5p mRNA was significantly decreased in A549 cells in LPS group, and the mRNA and protein expression of CXCR3 were significantly increased (p < .05). Overexpression of miR-16-5p and knockdown of CXCR3 both can down-regulated protein expression of IL-6 and TNF-α, and up-regulated apoptosis in LPS-induced A549 cell; CXCR3 is a target of miR-16-5p. Overexpression of CXCR3 rescued the protective effect of miR-16-5p on LPS-induced A549 cell injury. CONCLUSION: miR-16-5p can protect LPS-induced A549 cell injury, and its mechanism may be related to the targeted regulation of CXCR3, which could provide a new target for targeted therapy of lung cancer.

[Retracted] Serum­free­medium­type mesenchymal stem cell culture supernatant exerts a protective effect on A549 lung epithelial cells in acute lung injury induced by H2O2.

The authors wish to retract their research article entitled 'Serum­free­medium­type mesenchymal stem cell culture supernatant exerts a protective effect on A549 lung epithelial cells in acute lung injury induced by H2O2', published in Oncology Reports 40, 3033­3039, 2018. After the publication of this article, the authors have become concerned that there were flaws in their study design that have called into question the reported results. On repeating certain of the experiments, the authors found that the Nrf2­Keap1­ARE signaling pathway only has a role in the lung epithelial cell injury model, whereas it does not serve a role in the A549 model. Further studies are required to validate the role of the Nrf2­Keap1­ARE signaling pathway and the apoptosis­associated proteins. In particular, the results presented in Fig. 5, showing the difference between Bax and Bcl­2, appear to be incorrect. For these reasons, the authors have decided to retract the article from the publication. All the named authors on the paper agree to this retraction. The authors sincerely apologize for any inconvenience that might result from the retraction of this article. [the original article was published in the Oncology Reports 40: 3033­3039, 2018; DOI: 10.3892/or.2018.6656].

Mechanism of miR-137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene.

OBJECTIVE: To investigate the effect of microRNA-137 (miR-137) on the migration and invasion of melanoma cells and its mechanism. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-137 in melanoma tissues and cells. miR-137 mimics, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT-PCR and Western blot analysis. The Trans-well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR-137 and PIK3R3. RESULTS: Compared with normal pigmented nevus tissue, miR-137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR-137 was significantly decreased in melanoma SK-MEL-1, A375, and WM451 cells. Knockdown of miR-137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR-137. In addition, overexpression of miR-137-inhibited PIK3R3 expression, while knockdown of miR-137-enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR-137 on cell migration and invasive in melanoma A375 and WM451 cells. CONCLUSION: miR-137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene.

Astragaloside suppresses tumor necrosis factor receptor-associated factor 5 signaling pathway and alleviates neurodegenerative changes in retinal pigment epithelial cells induced by isoflurane.

Epidemiological studies showed that isoflurane, a general anesthetic widely used in surgery including those for the children, is associated with impairment of neurodevelopment and neurodegenerative diseases, such as Alzheimer's disease (AD) and age-related macular degeneration (AMD), which are related to the accumulation of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS. Cell cycle re-entry and proapoptosis were seen in retinal pigment epithelium (RPE) cells treated with isoflurane, which was alleviated by pretreatment of AS. Further, tumor necrosis factor receptor-associated factor 5 (TRAF5) and downstream nuclear factor-κB (NF-κB) were investigated to elucidate the molecular mechanism underlying protective effect of AS. RPE cells exposed to isoflurane expressed higher TRAF5 and NF-κB than those pretreated with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM) assay, Sprague-Dawley rats pretreated with AS and then exposed to isoflurane spent less time in swimming to the platform, and their TRAF5 expression was significantly lower than those received anesthesia alone. Further studies on the consequence of forced downregulation or upregulation are warranted that may employ cutting-edge technologies such as optogenetics to overcome the difficulties in manipulating expression of TRAF5. Although the link between TRAF5 and neurodegeneration requires more in-depth investigations, our study provide a novel hint on the pathological mechanism of isoflurane and suggest a potential target for eliminating persistent side effect of anesthesia.

microRNA-874 inhibition targeting STAT3 protects the heart from ischemia-reperfusion injury by attenuating cardiomyocyte apoptosis in a mouse model.

MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia-reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR-874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV. The functional mechanism of miR-874 in I/R injury was explored when miR-874 and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway were inhibited. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP biotin nick-end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis and dual luciferase reporter gene assay to identify the targeting relationship between miR-874 and STAT3. Expression of the JAK2/STAT3 signaling pathway and apoptosis-related genes was determined. Initially, upregulated miR-874 was observed in I/R mice. Then, miR-874 inhibition improved cardiac function of I/R mice, inhibited cardiomyocyte apoptosis (also shown as decreased Bcl-2 associated X protein B [Bax] and increased B-cell lymphoma-2 [Bcl-2]), and activated the JAK2/STAT3 signaling pathway. STAT3, a target gene of miR-874, was upregulated following miR-874 inhibition. Finally, we also observed that the effect of miR-874 was lost when the JAK2/STAT3 signaling pathway was blocked. The findings indicate miR-874 as a contributory role in cardiac I/R injury, with miR-874 inhibition alleviating cardiac I/R injury in mice following SEV pretreatment by targeting STAT3 through the JAK2/STAT3 signaling pathway.

Microbiota and Food Allergy.

Emerging evidence suggests that the increasing prevalence of food allergies is associated with compositional and functional changes in our gut microbiota. Microbiota-host interactions play a key role in regulating the immune system. Development of a healthy gut microbiota and immune system occurs early in life and is largely shaped by exposure to maternal microbes through vaginal/natural delivery and breast milk, whereas use of antibiotics can disrupt gut homeostasis and significantly raise the risk of allergic diseases. Thus, changes in the quantity or diversity of gut microbes affect oral toleranace through interations of microbial molecules with pattern recognition receptors on immune cells and confer susceptibility to food allergies. On the other hand, short chain fatty acids which are fermentation end products of insoluble fibers by intestinal micoorganisms have been shown to confer protective effects on food allergy. As a preventive and therapeutic treatment for food allergies, probiotics have gained widespread attention in recent years. Reintroducing certain commensal microbes, such as Clostridia, both in animal models and clinical trials led to the prevention or resolution of allergic symptoms. This review highlights recent progress in our understanding of the gut microbiota's role in food allergy. However, mechanistic details underlying the anti-allergic effects of probiotics and the interaction between the gut microbiota and the immune system remain circumstantial and are not fully understood. Future studies should address possible factors and underlying mechanisms for microbiota-host interactions and gut immunity, as well as the efficacy, safety, and appropriate use of probiotics in establishing a standard treatment regimen for food allergies.