A novel nomogram predicting overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in portal hypertension patients.

We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002-1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003-1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006-1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009-1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029-1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

CD4+ conventional T cells-related genes signature is a prognostic indicator for ovarian cancer.

Introduction: It is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC. Methods: We obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts. Results: High riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.

Deciphering the expression patterns of homologous recombination-related lncRNAs identifies new molecular subtypes and emerging therapeutic opportunities in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading killer among women with gynecologic malignancies. Homologous recombination deficiency (HRD) has attracted increasing attention due to its significant implication in the prediction of prognosis and response to treatments. In addition to the germline and somatic mutations of homologous recombination (HR) repair genes, to widely and deeply understand the molecular characteristics of HRD, we sought to screen the long non-coding RNAs (lncRNAs) with regard to HR repair genes and to establish a prognostic risk model for EOC. Herein, we retrieved the transcriptome data from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA) databases. HR-related lncRNAs (HRRlncRNAs) associated with prognosis were identified by co-expression and univariate Cox regression analyses. The least absolute shrinkage and selection operator (LASSO) and multivariate stepwise Cox regression were performed to construct an HRRlncRNA risk model containing AC138904.1, AP001001.1, AL603832.1, AC138932.1, and AC040169.1. Next, Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), nomogram, calibration, and DCA curves were made to verify and evaluate the model. Gene set enrichment analysis (GSEA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in the risk groups were also analyzed. The calibration plots showed a good concordance with the prognosis prediction. ROCs of 1-, 3-, and 5-year survival confirmed the well-predictive efficacy of this model in EOC. The risk score was used to divide the patients into high-risk and low-risk subgroups. The low-risk group patients tended to exhibit a lower immune infiltration status and a higher HRD score. Furthermore, consensus clustering analysis was employed to divide patients with EOC into three clusters based on the expression of the five HRRlncRNAs, which exhibited a significant difference in checkpoints' expression levels and the tumor microenvironment (TME) status. Taken together, the results of this project supported that the five HRRlncRNA models might function as a biomarker and prognostic indicator with respect to predicting the PARP inhibitor and immune treatment in EOC.

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro.

BACKGROUND: Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM: To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS: Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS: TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION: Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

Optimal Control of Time-Delay Fractional Equations via a Joint Application of Radial Basis Functions and Collocation Method.

A novel approach to solve optimal control problems dealing simultaneously with fractional differential equations and time delay is proposed in this work. More precisely, a set of global radial basis functions are firstly used to approximate the states and control variables in the problem. Then, a collocation method is applied to convert the time-delay fractional optimal control problem to a nonlinear programming one. By solving the resulting challenge, the unknown coefficients of the original one will be finally obtained. In this way, the proposed strategy introduces a very tunable framework for direct trajectory optimization, according to the discretization procedure and the range of arbitrary nodes. The algorithm's performance has been analyzed for several non-trivial examples, and the obtained results have shown that this scheme is more accurate, robust, and efficient than most previous methods.

Combination of endoscopic submucosal dissection and laparoscopic sentinel lymph node dissection in early mucinous gastric cancer: Role of lymph node metastasis.

BACKGROUND: Recent evidence showed that combining endoscopic submucosal dissection (ESD) and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer (EMGC) patients with risks of positive lymph node metastasis (pLNM). AIM: To explore the predictive factors for pLNM in EMGC, and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC. METHODS: Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016. Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors, providing odds ratio (OR) with 95% confidence interval. And the association between the number of predictors and the pLNM rate was also investigated. RESULTS: Depth of invasion (OR = 7.342, 1.127-33.256, P = 0.039), tumor diameter (OR = 9.158, 1.348-29.133, P = 0.044), and lymphatic vessel involvement (OR = 27.749, 1.821-33.143, P = 0.019) turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis. For patients with 1, 2, and 3 risk factors, the pLNM rates were 9.1%, 33.3%, and 75.0%, respectively. pLNM was not detected in seven patients without any of these risk factors. CONCLUSION: ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size ≤ 2 cm, and when lymphatic vessel involvement is absent by postoperative histological examination. Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.

Application of quantitative analysis of contrast-enhanced ultrasonography in the evaluation of acute radiation-induced liver damage.

The aim of the present study was to evaluate the microcirculation perfusion in patients with acute radiation-induced liver damage (RILD) and explore the feasibility of non-invasive evaluation of RILD using quantitative analysis of contrast-enhanced ultrasound (CEUS). Patients who successfully underwent three-dimensional conformal intensity-modulated radiotherapy for abdominal tumors were selected. CEUS was performed on the liver prior to and 2, 3 and 4 weeks after exposure, and the time-intensity curve (TIC) was obtained by quantitative analysis of CEUS. The time to peak (TTP), gradient (Grad) and area under the curve (AUC) were analyzed offline. The Grad of the CEUS TIC was decreased and TTP increased with the prolongation of the irradiation duration, with statistically significant differences between the values in the 2-, 3- and 4-week groups vs. those prior to exposure (P<0.05), as well as among the values of the 2-, 3- and 4-week groups (P<0.05). Following irradiation, the AUC decreased gradually in the 2- and 3-week groups and increased in the 4-week group, with statistically significant differences compared with the AUC prior to irradiation (P<0.05). The quantitative analysis parameters of CEUS may be important reference parameters for the early diagnosis of acute RILD.

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer.

AIM: To identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using endoscopic submucosal dissection (ESD) for the treatment of intramucosal poorly differentiated EGC. METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component. RESULTS: Tumor size (OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement (OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component (OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7 (8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors. CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.

Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model.

The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation.

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

MicroRNA-139-5p inhibits cell proliferation and invasion by targeting insulin-like growth factor 1 receptor in human non-small cell lung cancer.

INTRODUCTION: Increasing evidence suggested that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miRNA-139-5p has been observed in various types of cancers. However, the biological function of miRNA-139-5p in non-small cell lung cancer (NSCLC) is still largely unknown. METHODS: Quantitative real-time PCR (qRT-PCR) was used to explore the expression level of miRNA-139-5p in NSCLC tissues and cell lines. Then, we investigated the role of miRNA-139-5p to determine its potential roles on lung cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was performed to confirm the target gene of miRNA-139-5p and the results were validated in renal cancer cells. RESULTS: miRNA-139-5p was significantly decreased in NSCLC tissues and cell lines. Over-expression of miRNA-139-5p could inhibit lung cancer cell proliferation, migration, and invasion in vitro. Furthermore, we identified insulin-like growth factor 1 receptor (IGF1R) as a target of miR-139-5p and miR-139-5p function as a tumor suppressor via targeting IGF1R in NSCLC. CONCLUSIONS: Our results indicated that miR-139-5p acts as a tumor suppressor in NSCLC partially via down-regulating IGF1R expression.

Risk clinicopathological factors for lymph node metastasis in poorly differentiated early gastric cancer and their impact on laparoscopic wedge resection.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC), and enlarge the possibility of using laparoscopic wedge resection (LWR). METHODS: We retrospectively analyzed 85 patients with poorly differentiated EGC who underwent surgical resection between January 1992 and December 2010. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95%CI were calculated. We further examined the relationship between the positive number of the three significant predictive factors and the LNM rate. RESULTS: In the univariate analysis, tumor size (P = 0.011), depth of invasion (P = 0.007) and lymphatic vessel involvement (P < 0.001) were significantly associated with a higher rate of LNM. In the multivariate model, tumor size (OR = 7.125, 95%CI: 1.251-38.218, P = 0.041), depth of invasion (OR = 16.624, 95%CI: 1.571-82.134, P = 0.036) and lymphatic vessel involvement (OR = 39.112, 95%CI: 1.745-123.671, P = 0.011) were found to be independently risk clinicopathological factors for LNM. Of the 85 patients diagnosed with poorly differentiated EGC, 12 (14.1%) had LNM. The LNM rates were 5.7%, 42.9% and 57.1%, respectively in cases with one, two and three of the risk factors respectively in poorly differentiated EGC. There was no LNM in 29 patients without the three risk clinicopathological factors. CONCLUSION: LWR alone may be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size, and when lymphatic vessel involvement is absent at postoperative histological examination.

[Comparative study of laparoscopy-assisted Vechitti vaginoplasty and vaginoplasty with peritoneum].

OBJECTIVE: To compare the therapeutic effect of laparoscopy-assisted Vechitti vaginoplasty and vaginoplasty with peritoneum. METHODS: From Jan. 2005 to Mar. 2011, 43 cases of congenital absence of vagina were treated by laparoscopy-assisted modified Vechitti vaginoplasty (n = 26) and by laparoscopy-assisted vaginoplasty with peritoneum (n = 17). The duration of operation, the intraoperative blood loss, and the length, appearance of reconstructed vagina were compared between the two groups. RESULTS: All the patients were successfully treated with no complication. The mould fell out in one case in Vechitti group one month after operation, which was put back after 3 days of expansion with a smaller mould. The perineum appearance was not affected. The reconstructed vagina in both groups were wide with pink mucosa, good elasticity and smoothness. The intercourse process was satisfied. The duration of operation and intraoperative blood loss were less in Vechitti group than those in peritoneum group, but the reconstructed vagina length was (7.8 +/- 0.4) cm in Vechitti group, and (8.8 +/- 0.6) cm in peritoneum group, showing a significant difference (t = 6.45, P < 0.01). CONCLUSIONS: Compared with Vechitti vaginoplasty, the laparoscopy-assisted vaginoplasty with peritoneum is comparatively complicated with longer operative duration, but the reconstructed vagina is longer with better long-term effect.