Radiogenomics study to predict the nuclear grade of renal clear cell carcinoma.

Purpose: To develop models based on radiomics and genomics for predicting the histopathologic nuclear grade with localized clear cell renal cell carcinoma (ccRCC) and to assess whether macro-radiomics models can predict the microscopic pathological changes. Method: In this multi-institutional retrospective study, a computerized tomography (CT) radiomic model for nuclear grade prediction was developed. Utilizing a genomics analysis cohort, nuclear grade-associated gene modules were identified, and a gene model was constructed based on top 30 hub mRNA to predict the nuclear grade. Using a radiogenomic development cohort, biological pathways were enriched by hub genes and a radiogenomic map was created. Results: The four-features-based SVM model predicted nuclear grade with an area under the curve (AUC) score of 0.94 in validation sets, while a five-gene-based model predicted nuclear grade with an AUC of 0.73 in the genomics analysis cohort. A total of five gene modules were identified to be associated with the nuclear grade. Radiomic features were only associated with 271 out of 603 genes in five gene modules and eight top 30 hub genes. Differences existed in the enrichment pathway between associated and un-associated with radiomic features, which were associated with two genes of five-gene signatures in the mRNA model. Conclusion: The CT radiomics models exhibited higher predictive performance than mRNA models. The association between radiomic features and mRNA related to nuclear grade is not universal.

Artificial intelligence with magnetic resonance imaging for prediction of pathological complete response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis.

Purpose: The purpose of this study was to evaluate the diagnostic accuracy of artificial intelligence (AI) models with magnetic resonance imaging(MRI) in predicting pathological complete response(pCR) to neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer. Furthermore, assessed the methodological quality of the models. Methods: We searched PubMed, Embase, Cochrane Library, and Web of science for studies published before 21 June 2022, without any language restrictions. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools were used to assess the methodological quality of the included studies. We calculated pooled sensitivity and specificity using random-effects models, I2 values were used to measure heterogeneity, and subgroup analyses to explore potential sources of heterogeneity. Results: We selected 21 papers for inclusion in the meta-analysis from 1562 retrieved publications, with a total of 1873 people in the validation groups. The meta-analysis showed that AI models based on MRI predicted pCR to nCRT in patients with rectal cancer: a pooled area under the curve (AUC) 0.91 (95% CI, 0.88-0.93), sensitivity of 0.82(95% CI,0.71-0.90), pooled specificity 0.86(95% CI,0.80-0.91). In the subgroup analysis, the pooled AUC of the deep learning(DL) model was 0.97, the pooled AUC of the radiomics model was 0.85; the pooled AUC of the combined model with clinical factors was 0.92, and the pooled AUC of the radiomics model alone was 0.87. The mean RQS score of the included studies was 10.95, accounting for 30.4% of the total score. Conclusions: Radiomics is a promising noninvasive method with high value in predicting pathological response to nCRT in patients with rectal cancer. DL models have higher predictive accuracy than radiomics models, and combined models incorporating clinical factors have higher diagnostic accuracy than radiomics models alone. In the future, prospective, large-scale, multicenter investigations using radiomics approaches will strengthen the diagnostic power of pCR. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021285630.

Effectiveness of Trastuzumab Combined With Capecitabine Treatment in a Patient With Hilar Cholangiocarcinoma Complicated by Liver Metastases With an ERBB2-Activating Mutation: A Case Report.

The identification of ERBB2 (HER2) alteration in some solid tumors has become critically important due to the actionable events predictive of response to anti-HER2 therapy. However, the efficacy of ERBB2 mutated hilar cholangiocarcinoma (hCCA) against ERBB2 is rarely reported. Here we report a 76-year-old female diagnosed with hCCA complicated by liver metastases after radical resection. The next-generation sequencing assay showed that the tumor had an ERBB2 mutation. Then, the patient was treated with trastuzumab plus capecitabine. After 2 months of treatment, she had a partial response. Until now, the patient is still alive. This study has shown the potential of trastuzumab combined with capecitabine as an effective treatment for hilar cholangiocarcinoma complicated by liver metastases harboring ERBB2 alterations.

Knockdown of circ_0008344 contributes to radiosensitization in glioma via miR-433-3p/RNF2 axis.

Numerous studies have identified that circular RNAs (circRNAs) functioned as important regulators in tumor initiation, carcinogenesis, drug or radiation resistance. This study aims to reveal the function of circ_0008344 on radiosensitivity in glioma. The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for detecting the circ_0008344 and microRNA-433-3p (miR-433-3p) levels. Cell survival intensity and apoptosis were analyzed through colony formation assay and flow cytometry respectively. The protein levels were examined via Western blot. Dual-luciferase reporter assay was exploited for the analysis of target combination. Xenograft models were established in mice for circ_0008344 research in vivo. Our data showed that circ_0008344 level was signally increased in radioresistant glioma tissues and its down-regulation facilitated the susceptibility of glioma cells to radiation. Additionally, we found that circ_0008344 could interact with miR-433-3p and regulated radiosensitivity of glioma cells via sponging miR-433-3p. Ring finger protein 2 (RNF2) was proved to be a target of miR-433-3p and it was regulated by circ_0008344/miR-433-3p axis. The promotion of circ_0008344 knockdown on radiosensitivity was counteracted by RNF2 overexpression in glioma cells. Further experiment in vivo indicated that circ_0008344 down-regulation inhibited glioma growth and acted on miR-433-3p/RNF2 axis to enhance the radiosensitivity in glioma. These evidences manifested that knockdown of circ_0008344 exerted the radiosensitivity-promoting effect on glioma via the miR-433-3p-mediated RNF2 down-regulation, identifying circ_0008344 as a novel diagnostic biomarker of radioresistance and therapeutic target in glioma radiotherapy.

Gender differences in recovery consequences among heroin dependent patients after compulsory treatment programs.

Studies on recovery patterns and how baseline factors influence recovery consequences among heroin dependent patients have shown mixed results. This study is aimed at describing the gender differences in long-term recovery patterns and exploring the predictors of negative recovery consequences by gender among heroin dependent patients in Shanghai, China. At baseline, this study recruited 503 heroin dependent patients discharged from Shanghai compulsory rehabilitation facilities in 2007 and 2008. In this cohort study, the baseline data was then linked with participants' 5-year follow-up data from official records. Generalized Estimating Equations (GEE) were used to compare males with females in terms of the presence of negative consequences (incarceration, or readmission to compulsory treatment, or both), in the subsequent 5-years after their discharge from compulsory treatment. Ordinary least squares (OLS) regression was used to explore factors associated to the time length of negative consequences in 5 years after the discharge for males and females separately. Our findings indicate that female heroin dependent patients tend to have less negative recovery outcomes than male patients. Male patients with a life-time history of poly drug use and female patients with borderline personality disorder are especially at risk of incarceration and readmission into compulsory treatment programs.

Increased Neutrophil-Lymphocyte Ratio Is a Poor Prognostic Factor in Patients with Esophageal Cancer in a High Incidence Area in China.

BACKGROUND AND AIMS: Neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) have been assumed to be a marker to predict the survival of patients with different types of cancer. We undertook this study to verify the prognostic value of the NLR and the PLR for predicting the survival rate of patients with esophageal cancer in a high incidence area in China. METHODS: In total, 820 cases from a high incidence area that had pathologically confirmed esophageal cancers initially diagnosed at the Fourth Hospital of Hebei Medical University from 2007-2008 were analyzed. The medical record system was used to collect patient information regarding personal details, cancer type, treatment, and routine blood examinations at the time of admission. Follow-up evaluations were conducted by the established follow-up system at the hospital. We used Kaplan-Meier method to calculate overall survival (OS) rate. We used Cox regression analysis to analyze the factors that may affect the OS rate of the patients. SPSS 13.0 and Excel software packages were used for statistical analysis. RESULTS: In total, 864 cases were consistent with the inclusion criterion. At the end of the study, 820 cases received follow-up evaluation. Follow-up rate was 94.91%. Among the 820 cases, 334 died of esophageal cancer, whereas 486 remain alive as of March 15, 2014. Five-year OS rate of the patients with esophageal cancer was 40.66%. Patients in the NLR ≥3.5 group demonstrated shorter OS than patients in the NLR <3.5 group (53.2 vs. 33.4 months, p = 0.001). Multivariate analysis indicated that age, pathological type, TNM stage, surgery and NLR were all independent risk factors for esophageal cancer. OR of NLR ≥3.5 group was 1.287 (1.049-1.580). CONCLUSIONS: NLR may be an independent prognostic factor for esophageal cancer in high incidence areas.

Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity.

A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 µM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).

Prognostic significance of Bcl-xL gene expression in human colorectal cancer.

Bcl-xL is a pro-survival member of the Bcl-2 family that plays indispensable roles in regulating cell survival and apoptosis. It is overexpressed in many malignant tumors including colorectal cancer (CRC). However, it is still unclear if Bcl-xL can be used as an independent molecular marker for predicting the prognosis of CRC patients. In this study, reverse transcription-PCR assay was performed to detect the expression of Bcl-xL mRNA in CRC and corresponding non-tumor colon tissues. Immunohistochemistry was performed to detect the immunolocalization of Bcl-xL protein in sixty-eight primary CRC tissue samples. The association between Bcl-xL protein expression and clinicopathological factors of CRC patients was analyzed and the survival was assessed by the Kaplan-Meier method and proportional hazards model. The averaged level of Bcl-xL mRNA expression in CRC tissues (0.85±0.13) was significantly higher than that in non-tumor colon tissues (0.08±0.02). Immunohistochemical staining showed that the Bcl-xL protein was mainly located in the cytoplasm of tumor cells. The level of Bcl-xL protein expression was closely correlated with tumor differentiation (P=0.002), lymph node metastasis (P=0.010), venous permeation (P=0.004), and Duke's classification (P=0.021). Furthermore, patients with high Bcl-xL expression showed poorer overall survival than those with low Bcl-xL expression (P=0.016). Univariate and multivariate analysis indicated that the status of Bcl-xL protein expression might be an independent prognostic marker for CRC patients (P=0.032). Taken together, immunohistochemical assessment of status of Bcl-xL protein may offer a valuable approach for predicting survival after curative surgery for colorectal cancer.

Echocardiographic evaluation of cardiac rhabdomyoma in infants and children.

PURPOSE: The objective of this study was to demonstrate the clinical presentation, echocardiographic findings, and morbidity and mortality rates for cardiac rhabdomyoma in Chinese infants and children by using echocardiography. METHODS: Two-dimensional echocardiography was performed at our institution from 1992 through 1999 on 12,800 children under 15 years of age. The diagnoses of cardiac rhabdomyoma were made primarily by echocardiography based on the presence of multiple tumors, cardiac tumors associated with tuberous sclerosis (TS), or histopathologic examination of surgical specimens. All patients were evaluated with 2-dimensional and Doppler echocardiography and then on follow-up examination every 3-6 months. Complete tumor regression was defined as no tumor visible by echocardiography. Partial tumor regression was defined as a decrease in tumor size of at least 15% from the previously measured size. RESULTS: A total of 29 tumors were found in 11 patients, 8 of whom had either TS or a family history of TS in 1 or more first-degree relatives. There were 9 boys and 2 girls 1 day-6.5 years old; (mean, 1.1 years). Three patients (newborns with heart failure) died, 2 after emergency surgery and 1 of intractable heart failure. The remaining 8 patients were managed conservatively and monitored for a mean duration of 3.3 years. Follow-up studies revealed that, of the 22 tumors in these 8 patients, 7 completely regressed, 7 partially regressed, and 8 remained stable. Our results showed no relationship between the tumor location and the regression rate (p = 0.34). CONCLUSIONS: Cardiac rhabdomyoma often presents in TS patients with no major arrhythmia or hemodynamic obstruction. However, in symptomatic neonates with or without TS, cardiac rhabdomyoma is usually fatal. Meticulous prenatal screening and routine echocardiographic examinations of patients with TS can reveal subclinical or clinically occult cardiac rhabdomyomas.