Deep learning using contrast-enhanced ultrasound images to predict the nuclear grade of clear cell renal cell carcinoma.

PURPOSE: To assess the effectiveness of a deep learning model using contrastenhanced ultrasound (CEUS) images in distinguishing between low-grade (grade I and II) and high-grade (grade III and IV) clear cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted using CEUS images of 177 Fuhrmangraded ccRCCs (93 low-grade and 84 high-grade) from May 2017 to December 2020. A total of 6412 CEUS images were captured from the videos and normalized for subsequent analysis. A deep learning model using the RepVGG architecture was proposed to differentiate between low-grade and high-grade ccRCC. The model's performance was evaluated based on sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Class activation mapping (CAM) was used to visualize the specific areas that contribute to the model's predictions. RESULTS: For discriminating high-grade ccRCC from low-grade, the deep learning model achieved a sensitivity of 74.8%, specificity of 79.1%, accuracy of 77.0%, and an AUC of 0.852 in the test set. CONCLUSION: The deep learning model based on CEUS images can accurately differentiate between low-grade and high-grade ccRCC in a non-invasive manner.

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms.

Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs). In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC50) of PTL on the activity of UGT1A1 was determined to be 64.4 µM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (Ki) was determined to be 12.1 µM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug-drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.

Predicting the risk for colorectal cancer with personal characteristics and fecal immunochemical test.

We aimed to predict colorectal cancer (CRC) based on the demographic features and clinical correlates of personal symptoms and signs from Tianjin community-based CRC screening data.A total of 891,199 residents who were aged 60 to 74 and were screened in 2012 were enrolled. The Lasso logistic regression model was used to identify the predictors for CRC. Predictive validity was assessed by the receiver operating characteristic (ROC) curve. Bootstrapping method was also performed to validate this prediction model.CRC was best predicted by a model that included age, sex, education level, occupations, diarrhea, constipation, colon mucosa and bleeding, gallbladder disease, a stressful life event, family history of CRC, and a positive fecal immunochemical test (FIT). The area under curve (AUC) for the questionnaire with a FIT was 84% (95% CI: 82%-86%), followed by 76% (95% CI: 74%-79%) for a FIT alone, and 73% (95% CI: 71%-76%) for the questionnaire alone. With 500 bootstrap replications, the estimated optimism (<0.005) shows good discrimination in validation of prediction model.A risk prediction model for CRC based on a series of symptoms and signs related to enteric diseases in combination with a FIT was developed from first round of screening. The results of the current study are useful for increasing the awareness of high-risk subjects and for individual-risk-guided invitations or strategies to achieve mass screening for CRC.

Long non-coding RNA DILC suppresses cell proliferation and metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling.

Naso-intestinal tube is more effective in treating postoperative ileus than naso-gastric tube in elderly colorectal cancer patients.

OBJECTIVE: The objective of this study was to compare the effect of naso-intestinal tube and naso-gastric tube in relieving postoperative ileus in elderly patients with colorectal cancer. METHODS: Patients (n = 46) with ileus symptom following radical surgery for treating colorectal cancer were placed with either naso-intestinal tube at duodenum or conventional naso-gastric tube. Then, their waist perimeter, intra abdominal pressure, maximum diameter in bowls, length of time to pass flatus or passage of bowel movement or to return to diet, length of hospital stay, daily drainage, serum levels of lactic acid, hemoglobin, and creatinine as well were compared. RESULTS: Naso-intestinal tube placement is more effective than naso-gastric tube in relieving intra abdominal pressures, reducing maximum bowl diameter and waist circumference, correcting serum lactic acid levels, alleviating analgesia dependence, regaining serum albumin level, increasing drainage and shortening the time of length of hospital stay, passing flatus or faces, and time to return to diet. CONCLUSION: Naso-intestinal tube is effective in treating POI and shows advantage over conventional naso-gastric tube insertion.

Efficacy of Cranial Electrotherapy Stimulation Combined with Biofeedback Therapy in Patients with Functional Constipation.

BACKGROUND/AIMS: A large number of studies have shown that function constipation (FC) has an extremely high incidence of mental and psychological disorders. Cranial electrotherapy stimulation (CES) was applied to the treatment of psychological disorders such as anxiety and depression. We explored the effects of CES combined with biofeedback therapy (BFT) on the psychological state, clinical symptoms, and anorectal function in patients with FC. METHODS: A total of 74 patients with FC were randomly divided into 2 groups. The control group received BFT. CES combined with BFT was carried out in the experiment group. All patients were assessed using the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Wexner constipation score at baseline and the end of each course. Anorectal manometry and balloon expulsion tests were performed before and after treatment. RESULTS: After treatment, the participants in the experiment group had significantly lower score SAS, SDS, and Wexner constipation scores than the control group (all P < 0.05). The number of successful expulsion in the experiment group was larger than the control group (P = 0.016). CONCLUSIONS: CES combined with BFT was effective in improving the psychological status of anxiety, depression, and bowel symptoms in patients with FC.

miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer.

MicroRNAs (miRNAs) are a conserved class of small non-coding RNAs that play important roles in diverse biological processes, including chemoresistance. However, the molecular mechanism as to how miR-203 modulates the chemosensitivity to 5-fluorouracil (5-FU) in colorectal cancer is poorly known. In the present study, we found that miR-203 was downregulated in the 5-FU-resistant cell line LoVo/5-Fu, and was inversely correlated with the extent of 5-FU chemoresistance. Cytotoxicity assay showed that the inhibition of miR-203 expression enhanced 5-FU chemoresistance in colorectal cancer cells, while miR-203 overexpression increased 5-FU chemosensitivity. We then validated that thymidylate synthase (TYMS) was a direct target of miR-203 and miR-203 suppressed TYMS protein levels. Silencing of TYMS enhanced 5-FU chemosensitivity, similar to the roles of miR-203. Finally, we discovered that miR-203 increased the inhibitory effects of 5-FU on tumor growth in vivo. Overall, our data indicate that miR-203 enhances 5-FU chemosensitivity via the downregulation of TYMS in colorectal cancer and provide important insight into the mechanism of 5-FU resistance in colorectal cancer patients. More important, the present study suggests that miR-203 has the potential as a therapeutic strategy for 5-FU-resistant colorectal cancer.

mRNA expression of IGF-1 and IGF-1R in patients with colorectal adenocarcinoma and type 2 diabetes.

BACKGROUND AND AIMS: Increasing studies show that messenger RNA (mRNA) levels of local IGF-system are overexpressed in cancer tissue of patients with colorectal cancer (CRC). However, the influence of type 2 diabetes (T2DM) on the expression of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) mRNA in colorectal cancer tissue and adjacent non-cancerous tissue (ANCT) is unknown. The aim of this study was to assess mRNA expression of IGF-1 and IGF-1R in paired samples of cancer tissue and ANCT between colorectal adenocarcinoma (CA) patients with and without T2DM. METHODS: To quantify the levels of IGF-1 and IGF-1R mRNA in CA, we analyzed the expression of IGF-1 and IGF-1R mRNA levels in paired samples of cancer tissue and ANCT in CA patients with and without T2DM using real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: mRNA levels of IGF-1 and IGF-1R were significantly higher in cancer tissue compared with its ANCT in CA patients with and without T2DM. Compared with the CA group, significantly higher levels of IGF-1 and IGF-1R mRNA were observed in cancer tissue in CA with T2DM group. No significant differences were observed in the role of cancer locations, Dukes stages and diabetes duration on mRNA expression of IGF-1. After adjusting for age, gender and Dukes stages, multivariate analysis indicated IGF-1 mRNA level was a risk factor for prognosis (p <0.05). CONCLUSIONS: Our results support the hypothesis that IGF system plays an important role in CRC. Further larger studies are needed.

[Risk factors associated with stress ulcer bleeding in postoperative rectal cancer patients].

OBJECTIVE: To explore the influence factor of stress ulcer bleeding(SUB) in postoperative rectal cancer patients. METHODS: Clinical data of rectal cancer patients undergoing operation in our hospital were analyzed retrospectively. Patients were divided into case group and control group according to the postoperative occurrence of SUB. Univariate analysis combined with multivariate analysis were used to evaluate the influence factors. RESULTS: Chronic diseases incidence of case group was higher than that of control group. Except for renal failure, the incidence of postoperative complications of case group was higher than that of control group. Univariate analysis revealed that age, chronic disease, preoperative, and postoperative complications had statistical significant differences(P<0.05). Multivariate analysis identified that age(OR=2.893, 95%CI:1.118-5.543), drinking history(OR=3.839, 95%CI:1.012-6.654), preoperative chronic disease(OR=4.646, 95%CI:1.872-8.892), intraoperative bleeding volume(OR=5.129, 95%CI:2.829-9.328), occurrence of severe complications after surgery(OR=6.576, 95%CI:4.539-13.278), postoperative application of glucocorticoid(OR=2.978, 95%CI:1.013-4.512), preoperative application of non-steroidal anti-inflammatory drugs(OR=2.126, 95%CI:1.287-7.636) were risk factors for SUB in rectal cancer patients after operation. Postoperative prophylactic use antacids(OR=0.102, 95%CI:0.017-0.196) was protective factor for SUB patients. CONCLUSION: Effective measures should be taken for high-risk patients, in order to improve the prognosis of patients.

[Efficacy of postoperative chemoradiation for stage III low rectal cancer].

OBJECTIVE: To evaluate the efficacy of postoperative chemoradiation for stage III low rectal cancer. METHODS: A total of 132 patients with stage III low rectal cancer, including 69 males and 63 females, were identified and divided into two groups: group A received chemoradiation while group B underwent chemotherapy alone. RESULTS: Eighteen patients developed local recurrence after five years of follow-up, with 6 cases(8.3%) in group A and 12(22.2%) in group B(P<0.05). In patients with distant metastasis(n=65), 37(47.4%) were in group A and 28(51.9%) in group B, and the difference was not statistically significant(P>0.05). The 5-year survival rates for group A and group B were 47.4% and 29.6%, respectively(P<0.05). Radiation proctitis was found in 6 cases in group A. CONCLUSIONS: Postoperative chemoradiation can reduce local recurrence rate and improve 5-year survival compared to chemotherapy alone. However, it has little effect on the distant metastasis. Postoperative chemoradiation is safe and effective for low rectal cancer.

[Experience of laparoscopic total mesorectal excision for middle or low rectal cancer].

OBJECTIVE: To study the feasibility and safety of laparoscopic surgery for middle or low rectal cancer. METHODS: 83 patients with middle or low rectal cancer received laparoscopic surgery and 85 patients received conventional open surgery. The cutting edge of specimens and number of lymph nodes were analyzed retrospectively. RESULTS: The mean distance between resected margin and the tumor was 3.21 +/- 1.25 cm in laparoscopic operation group, while it was 1.15 +/- 1.11 cm in the open surgery group (P = 0.001). The mean number of disected lymph nodes was 12.53 +/- 1.88 in the laparoscopic operation group and 10.85 +/- 1.81 in the open operation group (P = 0.01). The incidence of postoperative complications was 12.0% in the laparoscopic operation group and 23.5% in the open operation group (P = 0.026). The mean time of food intake and using analgesics after surgery were 2.43 +/- 1.06 days and 2.53 +/- 1.01 days, respectively, in the laparoscopic operation group, while the corresponding figures were 3.67 +/- 1.13 days and 4.55 +/- 1.78 days, respectively, in the open operation group (P = 0.005, P = 0.008). CONCLUSION: Laparoscopic surgery is a safe and effective procedure for middle or low rectal cancer, with less postoperative complications and better recovery after treatment.

[Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region].

To investigate the possible association of mismatch repair gene single nucleotide polymorphisms (SNPs) with susceptibility to sporadic colorectal cancer (SCRC), the genotypes of hMLH1 394G/C, hMSH2 943-1G/A, hMSH2 1917T/G, and hMSH2 2783C/A were detected by PCR-denaturing high-performance liquid chromatography (DHPLC) in 600 SCRC patients and 600 healthy controls. The genotype distribution of hMSH2 2783C/A in SCRC patients (90%, 9%, and 1%) was significantly different from that in the controls (95%, 4.8%, and 0.23%; chi2 = 11.91, P < 0.01). Compared to hMSH2 2783C/C, genotypes C/A and A/A significantly increased the risk of developing SCRC (OR were 1.77 and 11.94, and the reanges of 95% CI were 1.03-3.03 and 1.38-103.2). When combined analysis of three SNPs was performed, the haplotype distribution in SCRC patients was significantly different from that in controls (chi2 = 38.38, P < 0.01). In reference to 394G/943-1G /2783C haplotype, 394G/943-1G /2783A haplotype contributed significantly to SCRC (OR = 2.18, 95% CI: 1.40-3.40). These results indicate that hMSH2 2783C/A polymorphism has potential to be a susceptibility factor for SCRC and the 394G/943-1G /2783A haplotype might increase the risk of developing SCRC.