Sintilimab combined with bevacizumab in relapsed or persistent ovarian clear cell carcinoma (INOVA): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma. METHODS: In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing. FINDINGS: Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred. INTERPRETATION: Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy. FUNDING: National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity.

BACKGROUND: Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins. Eribulin, a therapeutic agent for the treatment of metastatic breast cancer and liposarcoma, is a new choice of ADC payload with a distinct mechanism of action and safety profile. METHODS: We've generated a novel HER2-tageting eribulin-containing ADC, BB-1701. The potency of BB-1701 was tested in vitro and in vivo against cancer cells where HER2-expressing levels vary in a large range. Bystander killing effect and toxin-induced immunogenic cell death (ICD) of BB-1701 were also tested. RESULTS: In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher in vitro cytotoxicity in HER2-low cancer cell lines. BB-1701 also effectively suppressed tumors in models resistant to DM1 or Dxd containing ADCs. Mode of action studies showed that BB-1701 had a significant bystander effect on HER2-null cells adjacent to HER2-high cells. In addition, BB-1701 treatment induced ICD. Repeated doses of BB-1701 in nonhuman primates showed favorable pharmacokinetics and safety profiles at the intended clinical dosage, route of administration, and schedule. CONCLUSIONS: The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.

Evaluation of multiplexed sensitivity encoding diffusion-weighted imaging in detecting uterine lesions: Image quality optimization.

PURPOSE: To compare the image quality of multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE-DWI) and single-shot echo-planar imaging (SS-EPI-DWI) techniques in uterine MRI. METHODS: Eighty-eight eligible patients underwent MUSE-DWI and SS-EPI-DWI examinations simultaneously using a 3.0 T MRI system. Two radiologists independently performed quantitative and qualitative analysis of the two groups of images using a double-blind method. The weighted Kappa test was used to evaluate the interobserver agreement. Wilcoxon's rank sum test was used for qualitative parameters, and paired t-test was used for quantitative parameters. Spearman rank correlation analysis was used to obtained correlation between pathological results and mean apparent diffusion coefficient (ADC) value. RESULTS: The qualitative and quantitative analysis of the images by the two radiologists were in good or excellent agreement, with weighted kappa value ranging from 0.636 to 0.981. The scores of total subjective image quality (15.4 ± 0.99) and signal-to-noise ratio (158.99 ± 60.71) of MUSE-DWI were significantly higher than those of SS-EPI-DWI (12.93 ± 1.62 P < 0.001; 130.23 ± 48.29 P < 0.05). It effectively reduced image distortion and artifact, and had better lesion conspicuity. There was no significant difference in contrast-to-noise ratio score and average ADC values between the two DWI sequences. The average ADC values of the two DWI sequences were highest in the normal uterus group and lowest in the endometrial cancer group, with statistically significant differences among groups (P < 0.01). In addition, the average ADC values of the two DWI sequences were negatively correlated with the type of lesions, decreasing with the malignancy of the lesions (r = -0.805 P < 0.01, r = -0.815 P < 0.01). CONCLUSION: Compared to SS-EPI-DWI, MUSE-DWI can significantly reduce distortion, artifacts, and fuzziness in MRI of uterine lesions, which is more conducive to lesion detection.

Progress of Multiparameter Magnetic Resonance Imaging in Bladder Cancer: A Comprehensive Literature Review.

Magnetic resonance imaging (MRI) has been proven to be an indispensable imaging method in bladder cancer, and it can accurately identify muscular invasion of bladder cancer. Multiparameter MRI is a promising tool widely used for preoperative staging evaluation of bladder cancer. Vesical Imaging-Reporting and Data System (VI-RADS) scoring has proven to be a reliable tool for local staging of bladder cancer with high accuracy in preoperative staging, but VI-RADS still faces challenges and needs further improvement. Artificial intelligence (AI) holds great promise in improving the accuracy of diagnosis and predicting the prognosis of bladder cancer. Automated machine learning techniques based on radiomics features derived from MRI have been utilized in bladder cancer diagnosis and have demonstrated promising potential for practical implementation. Future work should focus on conducting more prospective, multicenter studies to validate the additional value of quantitative studies and optimize prediction models by combining other biomarkers, such as urine and serum biomarkers. This review assesses the value of multiparameter MRI in the accurate evaluation of muscular invasion of bladder cancer, as well as the current status and progress of its application in the evaluation of efficacy and prognosis.

[Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). METHODS: The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. RESULTS: Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ï¼»91.7%(33/36) vs 59.5%(22/37)ï¼½. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1ß level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that age（OR =0.917， 95%CI ：0.843-0.999, P =0.047）, thrombosis history (OR =34.148， 95%CI ：2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065， 95%CI ：1.217-212.024， P =0.035), and elevated level of IL-1ß (OR =0.929， 95%CI ：0.870-0.992， P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717， 95%CI ：2.690-292.482， P =0.012) and ASXL1 (OR =7.941， 95%CI ：1.045-60.353， P =0.045) were independent risk factors for CCEs in PV. CONCLUSION: There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1ß elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 ß elevated levels may be the novel risk factors for CCEs in MPN.

Evaluation of Whole-Tumor Texture Analysis Based on MRI Diffusion Kurtosis and Biparametric VI-RADS Model for Staging and Grading Bladder Cancer.

BACKGROUND: to evaluate the feasibility of texture analysis (TA) based on diffusion kurtosis imaging (DKI) in staging and grading bladder cancer (BC) and to compare it with apparent diffusion coefficient (ADC) and biparametric vesical imaging reporting and data system (VI-RADS). MATERIALS AND METHODS: In this retrospective study, 101 patients with pathologically confirmed BC underwent MRI with multiple-b values ranging from 0 to 2000 s/mm2. ADC- and DKI-derived parameters, including mean kurtosis (MK) and mean diffusivity (MD), were obtained. First-order texture histogram parameters of MK and MD, including the mean; 5th, 25th, 50th, 75th, and 90th percentiles; inhomogeneity; skewness: kurtosis; and entropy; were extracted. The VI-RADS score was evaluated based on the T2WI and DWI. The Mann-Whitney U-test was used to compare the texture parameters and ADC values between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), as well as between low and high grades. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of each significant parameter and their combinations. RESULTS: The NMIBC and low-grade group had higher MDmean, MD5th, MD25th, MD50th, MD75th, MD90th, and ADC values than those of the MIBC and the high-grade group. The NMIBC and low-grade group yielded lower MKmean, MK25th, MK50th, MK75th, and MK90th than the MIBC and high-grade group. Among all histogram parameters, MD75th and MD90th yielded the highest AUC in differentiating MIBC from NMIBC (both AUCs were 0.87), while the AUC for ADC was 0.86. The MK75th and MK90th had the highest AUC (both 0.79) in differentiating low- from high-grade BC, while ADC had an AUC of 0.68. The AUC (0.92) of the combination of DKI histogram parameters (MD75th, MD90th, and MK90th) with biparametric VI-RADS in staging BC was higher than that of the biparametric VI-RADS (0.89). CONCLUSIONS: Texture-analysis-derived DKI is useful in evaluating both the staging and grading of bladder cancer; in addition, the histogram parameters of the DKI (MD75th, MD90th, and MK90th) can provide additional value to VI-RADS.

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma.

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

Amide Proton Transfer-Weighted Imaging Combined with ZOOMit Diffusion Kurtosis Imaging in Predicting Lymph Node Metastasis of Cervical Cancer.

BACKGROUND: The aim of this study is to investigate the feasibility of amide proton transfer-weighted (APTw) imaging combined with ZOOMit diffusion kurtosis imaging (DKI) in predicting lymph node metastasis (LNM) in cervical cancer (CC). MATERIALS AND METHODS: Sixty-one participants with pathologically confirmed CC were included in this retrospective study. The APTw MRI and ZOOMit diffusion-weighted imaging (DWI) were acquired. The mean values of APTw and DKI parameters including mean kurtosis (MK) and mean diffusivity (MD) of the primary tumors were calculated. The parameters were compared between the LNM and non-LNM groups using the Student's t-test or Mann-Whitney U test. Binary logistic regression analysis was performed to determine the association between the LNM status and the risk factors. The diagnostic performance of these quantitative parameters and their combinations for predicting the LNM was assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: Patients were divided into the LNM group (n = 17) and the non-LNM group (n = 44). The LNM group presented significantly higher APTw (3.7 ± 1.1% vs. 2.4 ± 1.0%, p < 0.001), MK (1.065 ± 0.185 vs. 0.909 ± 0.189, p = 0.005) and lower MD (0.989 ± 0.195 × 10-3 mm2/s vs. 1.193 ± 0.337 ×10-3 mm2/s, p = 0.035) than the non-LNM group. APTw was an independent predictor (OR = 3.115, p = 0.039) for evaluating the lymph node status through multivariate analysis. The area under the curve (AUC) of APTw (0.807) was higher than those of MK (AUC, 0.715) and MD (AUC, 0.675) for discriminating LNM from non-LNM, but the differences were not significant (all p > 0.05). Moreover, the combination of APTw, MK, and MD yielded the highest AUC (0.864), with the corresponding sensitivity of 76.5% and specificity of 88.6%. CONCLUSION: APTw and ZOOMit DKI parameters may serve as potential noninvasive biomarkers in predicting LNM of CC.

Reduced field-of-view DWI­derived clinical-radiomics model for the prediction of stage in cervical cancer.

BACKGROUND: Pretreatment prediction of stage in patients with cervical cancer (CC) is vital for tailoring treatment strategy. This study aimed to explore the feasibility of a model combining reduced field-of-view (rFOV) diffusion-weighted imaging (DWI)-derived radiomics with clinical features in staging CC. METHODS: Patients with pathologically proven CC were enrolled in this retrospective study. The rFOV DWI with b values of 0 and 800 s/mm2 was acquired and the clinical characteristics of each patient were collected. Radiomics features were extracted from the apparent diffusion coefficient maps and key features were selected subsequently. A clinical-radiomics model combining radiomics with clinical features was constructed. The receiver operating characteristic curve was introduced to evaluate the predictive efficacy of the model, followed by comparisons with the MR-based subjective stage assessment (radiological model). RESULTS: Ninety-four patients were analyzed and divided into training (n = 61) and testing (n = 33) cohorts. In the training cohort, the area under the curve (AUC) of clinical-radiomics model (AUC = 0.877) for staging CC was similar to that of radiomics model (AUC = 0.867), but significantly higher than that of clinical model (AUC = 0.673). In the testing cohort, the clinical-radiomics model yielded the highest predictive performance (AUC = 0.887) of staging CC, even without a statistically significant difference when compared with the clinical model (AUC = 0.793), radiomics model (AUC = 0.846), or radiological model (AUC = 0.823). CONCLUSIONS: The rFOV DWI-derived clinical-radiomics model has the potential for staging CC, thereby facilitating clinical decision-making.

Comparison of outcomes between single- and multiple-perforator-based free perforator flaps: A systematic review and meta-analysis.

BACKGROUND: Perforator-based free perforator flaps have become an important tool for the reconstruction of tissue defects. The effect of the number of perforators on the outcomes of perforator flaps has been widely debated. This study aimed to compare the outcomes of single- and multiple-perforator-based free perforator flaps in free-flap reconstruction. METHODS: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database (CBM), Cochrane Library, and clinicaltrials.gov between January 2000 and June 2021 to identify studies that reported data on the outcomes of free perforator flaps. Two authors individually extracted data and performed quality assessment. Outcomes, including partial flap loss, total loss, fat necrosis, arterial insufficiency, venous insufficiency, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications, were evaluated. RESULTS: Thirty-two studies with 2498 flaps were included in our analysis. No significant difference was found in the rates of partial loss and arterial insufficiency of flaps, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications. However, the multiple-perforator group showed significantly lower rates of total loss (relative risk [RR] = 1.08, 95% confidence interval [CI]: 0.78-1.79, p = .754), fat necrosis (RR = 1.79, 95% [CI]: 1.36-2.36, p = .000) and venous insufficiency (RR = 1.72, 95% CI: 1.07-2.79, p = .026) than the single-perforator group. CONCLUSION: The rates of total loss, fat necrosis and venous insufficiency in the multiple-perforator group were lower than those in the single-perforator group. Hence, we recommend that multiple perforators be included in the free perforator flap when appropriate, to yield better clinical outcomes in reconstruction.

WHO/ISUP grade and pathological T stage of clear cell renal cell carcinoma: value of ZOOMit diffusion kurtosis imaging and chemical exchange saturation transfer imaging.

OBJECTIVES: To evaluate the value of ZOOMit diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) imaging in predicting WHO/ISUP grade and pathological T stage in clear cell renal cell carcinoma (ccRCC). METHODS: Forty-six patients with ccRCC were included in this retrospective study. All participants underwent MRI including ZOOMit DKI and CEST. The non-Gaussian mean kurtosis (MK), mean diffusivity (MD), magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)), and Ssat (3.5 ppm)/S0 were analyzed based on different WHO/ISUP grades and pT stages. Binary logistic regression was used to identify the best combination of the parameters. Pearson's correlation coefficients were calculated between CEST and diffusion-related parameters. RESULTS: The ADC, MD, and Ssat (3.5 ppm)/S0 values were significantly lower for higher WHO/ISUP grade tumors, whereas the MK and MTRasym (3.5 ppm) were higher in higher WHO/ISUP grade and higher pT stage tumors. MTRasym (3.5 ppm) combined with MD (AUC, 0.930; 95% CI, 0.858-1.000) showed the best diagnostic efficacy in evaluating the WHO/ISUP grade. MTRasym (3.5 ppm) and MK were mildly positively correlated (r = 0.324, p = 0.028). Ssat (3.5 ppm)/S0 was moderately positively correlated with ADC (r = 0.580, p < 0.001), mildly positively correlated with MD (r = 0.412, p = 0.005), and moderately negatively correlated with MK (r = -0.575, p < .001). CONCLUSION: The microstructural and biochemical assessment of ZOOMit DKI and CEST allowed for the characterization of different WHO/ISUP grades and pT stages in ccRCC. MTRasym (3.5 ppm) combined with MD showed the best diagnostic performance for WHO/ISUP grading. KEY POINTS: • Both diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) can be used to predict the WHO/ISUP grade and pathological T stage. • MTRasym (3.5 ppm) combined with MD showed the highest AUC (0.930; 95% CI, 0.858-1.000) in WHO/ISUP grading. • MTRasym at 3.5 ppm showed a positive correlation with mean kurtosis.

Whole-Lesion CT Texture Analysis as a Quantitative Biomarker for the Identification of Homogeneous Renal Tumors.

Renal tumors are very common in the urinary system, and the preoperative differential diagnosis of homogeneous renal tumors remains a challenge. This study aimed to evaluate the feasibility of the whole-lesion CT texture analysis for the identification of homogeneous renal tumors including clear cell renal cell carcinoma (ccRCC), chromophobe RCC (chRCC), and renal oncocytoma (RO). This retrospective study was approved by our local IRB. Contrast-enhanced CT examination was performed in 128 patients and histopathologically confirmed ccRCC, chRCC, and RO. The one-way ANOVA test with Bonferroni corrections was used to compare the differences, and the receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic efficiency. The whole-lesion CT histogram analysis was used to demonstrate significant differences between ccRCC and chRCC in both arterial and venous phases, and the entropy demonstrated excellent performance in discriminating these two types of tumors (AUCs = 0.95, 0.91). The inhomogeneity of ccRCC was significantly higher than that of RO both in arterial and venous phases. The entropy of chRCC was significantly lower than that of RO, and the kurtosis and entropy yielded high sensitivity (91%) and moderate specificity (74%) in the arterial phase. The whole-lesion CT histogram analysis could be useful for the differential diagnosis of homogeneous ccRCC, chRCC, and RO.

Radiomics Nomogram Based on High-b-Value Diffusion-Weighted Imaging for Distinguishing the Grade of Bladder Cancer.

BACKGROUND: The aim was to evaluate the feasibility of radiomics features based on diffusion-weighted imaging (DWI) at high b-values for grading bladder cancer and to compare the possible advantages of high-b-value DWI over the standard b-value DWI. METHODS: Seventy-four participants with bladder cancer were included in this study. DWI sequences using a 3 T MRI with b-values of 1000, 1700, and 3000 s/mm2 were acquired, and the corresponding ADC maps were generated, followed with feature extraction. Patients were randomly divided into training and testing cohorts with a ratio of 8:2. The radiomics features acquired from the ADC1000, ADC1700, and ADC3000 maps were compared between low- and high-grade bladder cancers by using the Wilcox analysis, and only the radiomics features with significant differences were selected. The least absolute shrinkage and selection operator method and a logistic regression were performed for the feature selection and establishing the radiomics model. A receiver operating characteristic (ROC) analysis was conducted to assess the diagnostic performance of the radiomics models. RESULTS: In the training cohorts, the AUCs of the ADC1000, ADC1700, and ADC3000 model for discriminating between low- from high-grade bladder cancer were 0.901, 0.920, and 0.901, respectively. In the testing cohorts, the AUCs of ADC1000, ADC1700, and ADC3000 were 0.582, 0.745, and 0.745, respectively. CONCLUSIONS: The radiomics features extracted from the ADC1700 maps could improve the diagnostic accuracy over those extracted from the conventional ADC1000 maps.

Therapeutic potential and research progress of diosgenin for lipid metabolism diseases.

Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.

The Lactobacillus gasseri G098 Strain Mitigates Symptoms of DSS-Induced Inflammatory Bowel Disease in Mice.

Inflammatory bowel disease (IBD) is a recurring inflammatory disease of the gastrointestinal tract with unclear etiology, but it is thought to be related to factors like immune abnormalities and gut microbial dysbiosis. Probiotics can regulate host immunity and gut microbiota; thus, we investigated the alleviation effect and mechanism of the strain Lactobacillus gasseri G098 (G098) on dextran sodium sulfate (DSS)-induced colitis in mice. Three groups of mice (n = 8 per group) were included: normal control (NC), DSS-induced colitis mice (DSS), and colitis mice given strain (G098). Our results showed that administering G098 effectively reversed DSS-induced colitis-associated symptoms (mitigating weight loss, reducing disease activity index and pathology scores; p < 0.05 in all cases) and prevented DSS-induced mortality (62.5% in DSS group; 100% in G098 group). The mortality rate and symptom improvement by G098 administration was accompanied by a healthier serum cytokine balance (significant decreases in serum pro-inflammatory factors, interleukin (IL)-6 [p < 0.05], IL-1ß [p < 0.01], and tumor necrosis factor (TNF)-α [p < 0.001], and significant increase in the serum anti-inflammatory factor IL-13 [p < 0.01], compared with DSS group) and gut microbiome modulation (characterized by a higher gut microbiota diversity [p < 0.05], significantly more Firmicutes and Lachnoclostridium [p < 0.05], significantly fewer Bacteroidetes [p < 0.05], and significant higher gene abundances of sugar degradation-related pathways [p < 0.05], compared with DSS-treated group). Taken altogether, our results suggested that G098 intake could mitigate DSS-induced colitis through modulating host immunity and gut microbiome, and strain treatment is a promising strategy for managing IBD.

Comparing donor site morbidity between radial and ulnar forearm free flaps: a meta-analysis.

The vascularised forearm free flap is a workhorse flap for the reconstruction of many types of soft tissue defects. However, the difference in donor-site morbidity between the radial forearm free flap (RFFF) and ulnar forearm free flap (UFFF) remains controversial. This study aimed to compare the donor-site outcomes of RFFF and UFFF. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, Cochrane Library, and Chinese Biomedical Literature Database up to August 10, 2021, to identify studies on donor-site outcomes of RFFF versus UFFF in patients undergoing reconstructive surgery. Two authors individually extracted data and performed quality assessments of the selected articles. The overall morbidity and overall effect of individual complications of the donor site were analysed. In total, 288 cases from five studies were included in our analysis. The UFFF group was significantly superior to the RFFF group regarding overall morbidity and overall effect of individual complications of the donor site. The morbidity of UFFF donor sites was significantly lower than that of RFFF, and UFFF may be an ideal substitute for RFFF in reconstructive surgery. However, additional large-scale studies are necessary to confirm this finding.

Accuracy and Challenges in the Vesical Imaging-Reporting and Data System for Staging Bladder Cancer.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) scoring system has been widely used to stage bladder cancer (BCa) since 2018. PURPOSE: To describe the characteristics of cases with discordant T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) scores in patients with BCa and further verify the accuracy of the VI-RADS scoring system and the necessity of dynamic contrast-enhanced (DCE) sequence. STUDY TYPE: Retrospective. SUBJECTS: A total of 106 patients (include 16.5% female) with bladder cancer. SEQUENCE: T2WI (fast spin echo), DWI (echo planer imaging), and DCE (gradient echo). ASSESSMENT: Some cases are difficult to score according to the system, mainly when the T2WI (category 4) and DWI (category 2) sequence scores are discordant, termed the discordant group below. The complementary group will be termed concordant group. Each MRI sequence was reviewed respectively according to the 5-point VI-RADS scoring system by three observers. The diagnostic ability of sequences for evaluating muscle invasion by BCa was calculated using histopathology as the reference standards. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, DeLong test, intraclass correlation coefficient. A P value of 0.05 or less was considered statistically significant. RESULTS: Fourteen cases (13.2%) had discordant VI-RADS scoring system. In the discordant group, the area under the ROC curve (AUC) of DCE was 0.875, while the T2WI and DWI showed limited diagnostic performance (AUCs = 0.50). In the concordant group, there was no significant difference in diagnostic efficacy between the overall VI-RADS (AUC: 0.950) and the combination of T2WI and DWI (AUC: 0.946) (P = 0.56). Among all patients, the AUC of overall VIRADS was 0.939 with a 3 or greater cutoff value. DATA CONCLUSION: The DCE was crucial in the discordant group for evaluating muscle-invasiveness, while DCE may not be necessary for the concordant group. The VI-RADS scoring system performed with overall good diagnostic performance in evaluating muscle-invasiveness in BCa patients. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Evaluation of a fractional-order calculus diffusion model and bi-parametric VI-RADS for staging and grading bladder urothelial carcinoma.

OBJECTIVES: To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS). METHODS: Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0-3600 s/mm2), were analyzed using the FROC model. Three FROC parameters, D, ß, and µ, were used for delineating NMIBC from MIBC and for tumor grading. A receiver operating characteristic (ROC) analysis was performed based on the individual FROC parameters and their combinations, followed by comparisons with apparent diffusion coefficient (ADC) and bi-parametric VI-RADS based on T2-weighted images and DWI. RESULTS: D and µ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, ß, and µ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, ß, and µ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931. CONCLUSIONS: High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors. KEY POINTS: • Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and µ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.

Clinical and Radiological Features of Urachal Carcinoma and Infection.

PURPOSE: To explore the clinical and radiological differences between urachal carcinoma and urachal infection. METHODS: Clinical and imaging information for 13 cases of urachal carcinoma and 14 cases of urachal infection confirmed by pathology were retrospectively analyzed. The size, location, shape, margin, lesion composition, calcification, T1 and T2 signal intensity, peripheral lymph nodes, degree of enhancement, adjacent bladder wall, and apparent diffusion coefficient (ADC) value were examined in both groups, and distinguish features were determined. The student t-test or Mann-Whitney U test was used for quantitative data, and Fisher's exact test was used for qualitative data. Kappa coefficient consistency test was used to evaluate the interobserver agreement. RESULTS: Sex, hematuria, abdominal pain, calcification, and thickening of adjacent bladder wall can distinguish between urachal carcinoma and urachal infection (p < 0.05). There were no statistical differences in age (p = 0.076), size (p = 0.797), location (p = 0.440), shape (p = 0.449), margin (p = 0.449), lesion composition (p = 0.459), T1 signal intensity (p = 0.196), T2 signal intensity (p = 0.555), peripheral lymph nodes (p = 0.236), degree of enhancements (p = 0.184) and ADC value (p = 0.780) between two groups. CONCLUSION: The following clinical and imaging features help distinguish urachal carcinoma from urachal infection: sex, hematuria, abdominal pain, calcification, and thickening of the adjacent bladder wall.

Glucosamine Ameliorates Symptoms of High-Fat Diet-Fed Mice by Reversing Imbalanced Gut Microbiota.

Glucosamine (GlcN) is used as a supplement for arthritis and joint pain and has been proved to have effects on inflammation, cancer, and cardiovascular diseases. However, there are limited studies on the regulatory mechanism of GlcN against glucose and lipid metabolism disorder. In this study, we treated high-fat diet (HFD)-induced diabetic mice with GlcN (1 mg/ml, in drinking water) for five months. The results show that GlcN significantly reduced the fasting blood glucose of HFD-fed mice and improved glucose tolerance. The feces of intestinal contents in mice were analyzed using 16s rDNA sequencing. It was indicated that GlcN reversed the imbalanced gut microbiota in HFD-fed mice. Based on the PICRUSt assay, the signaling pathways of glucolipid metabolism and biosynthesis were changed in mice with HFD feeding. By quantitative real-time PCR (qPCR) and hematoxylin and eosin (H&E) staining, it was demonstrated that GlcN not only inhibited the inflammatory responses of colon and white adipose tissues, but also improved the intestinal barrier damage of HFD-fed mice. Finally, the correlation analysis suggests the most significantly changed intestinal bacteria were positively or negatively related to the occurrence of inflammation in the colon and fat tissues of HFD-fed mice. In summary, our studies provide a theoretical basis for the potential application of GlcN to glucolipid metabolism disorder through the regulation of gut microbiota.