Copy number amplification-induced overexpression of lncRNA LOC101927668 facilitates colorectal cancer progression by recruiting hnRNPD to disrupt RBM47/p53/p21 signaling.

BACKGROUND: Somatic copy number alterations (SCNAs) are pivotal in cancer progression and patient prognosis. Dysregulated long non-coding RNAs (lncRNAs), modulated by SCNAs, significantly impact tumorigenesis, including colorectal cancer (CRC). Nonetheless, the functional significance of lncRNAs induced by SCNAs in CRC remains largely unexplored. METHODS: The dysregulated lncRNA LOC101927668, induced by copy number amplification, was identified through comprehensive bioinformatic analyses utilizing multidimensional data. Subsequent in situ hybridization was employed to ascertain the subcellular localization of LOC101927668, and gain- and loss-of-function experiments were conducted to elucidate its role in CRC progression. The downstream targets and signaling pathway influenced by LOC101927668 were identified and validated through a comprehensive approach, encompassing RNA sequencing, RT-qPCR, Western blot analysis, dual-luciferase reporter assay, evaluation of mRNA and protein degradation, and rescue experiments. Analysis of AU-rich elements (AREs) within the mRNA 3' untranslated region (UTR) of the downstream target, along with exploration of putative ARE-binding proteins, was conducted. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and dual-luciferase reporter assays were employed to elucidate potential interacting proteins of LOC101927668 and further delineate the regulatory mechanism between LOC101927668 and its downstream target. Moreover, subcutaneous xenograft and orthotopic liver xenograft tumor models were utilized to evaluate the in vivo impact of LOC101927668 on CRC cells and investigate its correlation with downstream targets. RESULTS: Significantly overexpressed LOC101927668, driven by chr7p22.3-p14.3 amplification, was markedly correlated with unfavorable clinical outcomes in our CRC patient cohort, as well as in TCGA and GEO datasets. Moreover, we demonstrated that enforced expression of LOC101927668 significantly enhanced cell proliferation, migration, and invasion, while its depletion impeded these processes in a p53-dependent manner. Mechanistically, nucleus-localized LOC101927668 recruited hnRNPD and translocated to the cytoplasm, accelerating the destabilization of RBM47 mRNA, a transcription factor of p53. As a nucleocytoplasmic shuttling protein, hnRNPD mediated RBM47 destabilization by binding to the ARE motif within RBM47 3'UTR, thereby suppressing the p53 signaling pathway and facilitating CRC progression. CONCLUSIONS: The overexpression of LOC101927668, driven by SCNAs, facilitates CRC proliferation and metastasis by recruiting hnRNPD, thus perturbing the RBM47/p53/p21 signaling pathway. These findings underscore the pivotal roles of LOC101927668 and highlight its therapeutic potential in anti-CRC interventions.

Dissociation of Nicotine from Acetylcholine-Binding Protein under Terahertz Waves Radiation.

The binding of nicotine (NCT) to acetylcholine-binding protein (AChBP) plays an important role in synaptic transmission and neurotransmitter regulation. However, effectively regulating their binding or dissociation processes remains a challenging problem. In this study, we employed all-atom molecular dynamics (MD) simulations to systematically investigate the impact of external terahertz (THz) waves on the binding kinetics between AChBP and NCT. We first identified the key residues (i.e., W143) and the key interactions (i.e., hydrogen bonding and cation-π interaction) in AChBP-NCT binding without THz waves. We then investigated the binding and dissociation of charged NCT with AChBP at three different frequencies (i.e., 13.02, 21.44, 42.55 THz). Importantly, the predominant vibrational modes at 13.02 THz can drive the rotation of the pentagonal ring on NCT. This leads to the disruption of hydrogen bonds between NCT and W143 and a reduced likelihood of forming cation-π interactions, resulting in the dissociation of NCT from AChBP. Additionally, we further investigated the influence of electric field intensities on the dissociation kinetics and found that when the electric field intensity exceeds a critical value (∼0.60 V/nm), the probability of ligand dissociation gradually rises as the intensity increases. In general, this study contributes to a better understanding of the effects of THz waves on protein-ligand interactions, which might also shed some light on potential applications in nicotine addiction treatment and therapeutic strategies for neurodegenerative diseases.

[Thulium laser enucleation versus plasma kinetic resection of the prostate in the treatment of benign prostatic hyperplasia].

OBJECTIVE: To compare thulium laser enucleation of the prostate (ThuLEP) with plasma kinetic resection of the prostate (PKRP) in the treatment of BPH. METHODS: We retrospectively analyzed the medical records of 160 cases of BPH treated by ThuLEP (the observation group, n = 80) or PKRP (the control group, n = 80) in our hospital from January 2021 to December 2023. We recorded the operation time, bladder irrigation time, catheter retention time, hospitalization time, postoperative complications, and pre- and postoperative maximum urinary flow rate (Qmax), residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume, followed by comparison of the data obtained between the two groups of patients. RESULTS: Compared with the controls, the patients of the observation group showed significantly shorter operation time (ï¼»67.25 ± 7.24ï¼½ vs ï¼»60.10 ± 5.15ï¼½ min, P< 0.05), bladder irrigation time (ï¼»46.90 ± 10.77ï¼½ vs ï¼»43.24 ± 6.65ï¼½ h, P< 0.05), catheterization time (ï¼»5.60 ± 1.31ï¼½ vs ï¼»5.03 ± 1.24ï¼½ d, P< 0.05) and hospitalization time (ï¼»7.31 ± 2.00ï¼½ vs ï¼»6.55 ± 1.67ï¼½ d, P< 0.05), higher Qmax (ï¼»18.50 ± 1.24ï¼½ vs ï¼»20.68 ± 1.45ï¼½ ml/s, P< 0.05), lower PVR (ï¼»12.10 ± 3.53ï¼½ vs ï¼»10.82 ± 3.10ï¼½ ml, P< 0.05), PSA (ï¼»4.60 ± 0.78ï¼½ vs ï¼»3.38 ± 0.40ï¼½ µg/L, P< 0.05) and prostate volume (ï¼»25.35 ± 6.46ï¼½ vs ï¼»20.12 ± 5.13ï¼½ ml, P< 0.05) at 3 months after surgery, but no statistically significant difference in the total incidence of postoperative complications (7.50% ï¼»6/80ï¼½ vs 5.00% ï¼»4/80ï¼½, P > 0.05). CONCLUSION: ThuLEP, with its advantages of notable effect, short operation and hospitalization time, significant improvement of urinary flow dynamics and prostate function, deserves clinical promotion for the treatment of BPH.

Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer.

BACKGROUND: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC. METHODS: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR. RESULTS: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway. CONCLUSIONS: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

Controllable construction of ZIF-derived Co9S8 hollow polyporous polyhedrons with Ru-doping for enhanced hydrogen evolution reaction.

Ru-doped Co9S8 hollow porous polyhedrons (Ru-Co9S8 HPPs) derived from zeolitic-imidazolate-frameworks were synthesized through hydrothermal coprecipitation and thermal decomposition methods. The results indicate that Ru-Co9S8-500 HPPs possess a strong Ru-Co synergistic effect, large electrochemical surface area, and sufficient active sites, endowing them with excellent hydrogen evolution reaction performance.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

PURPOSE: To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). METHODS: This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. RESULT: We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. CONCLUSION: The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice.

We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

Quantitative analysis of pre-treatment dynamic contrast-enhanced ultrasound for assessing the response of colorectal liver metastases to chemotherapy plus targeted therapy: a dual-institutional study.

OBJECTIVES: To investigate the clinical value of pre-treatment quantitative contrast-enhanced ultrasound (CEUS) in assessing the response of colorectal liver metastases (CRLM) to chemotherapy plus targeted therapy. METHODS: This study retrospectively enrolled 50 CRLM patients from the Zhongshan Hospital, Fudan University as the training cohort and 14 patients from Shanghai Tenth People's Hospital as the testing cohort. Patients underwent the CEUS examination before receiving chemotherapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI) plus targeted therapy (Bevacizumab or Cetuximab). The therapy response was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 based on pre-treatment CT and 3-month follow-up CT after therapy. Dynamic analysis was performed by VueBox® software. Time-intensity curves with quantitative perfusion parameters were obtained. In the training cohort, univariable and multivariable logistic regression analyses were used to develop the predictive model of therapy response. The predictive performance of the developed model was validated in the testing cohort. RESULTS: After the logistic regression analyses, the peak enhancement (PE) (odds ratio = 1.640; 95% confidence intervals [CI] 1.022-2.633) and time to peak (TTP) (odds ratio = 0.495; 95% CI 0.246-0.996) were determined as independent predictive factors. PE and TTP generated from VueBox® were not affected by ultrasound instruments and contrast agent dosage in therapy response evaluation (P > 0.05). The logistic regression model achieved satisfactory prediction performance (area under the curve: 0.923 in the training cohort and 0.854 in the testing cohort). CONCLUSION: CEUS with dynamic quantitative perfusion analysis, which presents high consistency, has potential practical value in predicting the response of CRLM to chemotherapy plus targeted therapy.

Response Evaluation Using Contrast-Enhanced Ultrasound for Unresectable Advanced Hepatocellular Carcinoma Treated With Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy.

OBJECTIVE: The aim of the work described here was to evaluate the role of contrast-enhanced ultrasound (CEUS) in response evaluation for unresectable advanced hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors (TKIs) plus anti-programmed cell death protein-1 (PD-1) antibody therapy. METHODS: A prospective cohort of consecutive patients with HCC who received combined TKI/anti-PD-1 antibody treatment for unresectable HCC between January 2022 and October 2022 was included in this study. The patients underwent unenhanced ultrasound (US) and CEUS examinations before treatment and at follow-up. Changes in the largest diameters of the target tumor on unenhanced US and the largest diameters of the enhancing target tumors on CEUS were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with unenhanced US and magnetic resonance imaging/computed tomography (MRI/CT) and modified RECIST (mRECIST) with CEUS and CEMRI/CT were used to assess treatment response. RESULTS: A total of 24 HCC patients (23 men and 1 woman; mean age: 56.5 ± 8.5 y; Barcelona Clinic Liver Cancer stage C, 62.5%; 29 intrahepatic target tumors) were studied. Calculations of degree of necrosis in the target tumors revealed no significant differences between CEUS and CEMRI/CT (44.5 ± 36.2% vs. 45.3 ± 36.8%, p = 0.862). As for the differentiation of responders from non-responders, the agreement between RECIST version 1.1 of unenhanced US and mRECIST-CEUS was poor (κ coefficient = 0.233). Meanwhile, there was a high degree of concordance between mRECIST-CEUS and mRECIST-CEMRI/CT (κ coefficient = 0.812). CONCLUSION: CEUS proved to be superior to baseline US and is comparable to CEMRI/CT in defining treatment outcome for combined TKI/anti-PD-1 antibody therapy.

Tandem Mass Tag-Based Proteomic Profiling Identifies Biomarkers in Drainage Fluid for Early Detection of Anastomotic Leakage after Rectal Cancer Resection.

Anastomotic leakage (AL), one of the most severe complications in rectal surgery, is often diagnosed late because of the low specificity of the clinical symptoms and limitations of current clinical investigations. Identification of patients with early AL remains challenging. Here, we explored the protein expression profiles of AL patients to provide potential biomarkers to identify AL in patients who undergo surgery for rectal cancer. We screened differentially expressed proteins (DEPs) in drainage fluid from AL and non-AL patients using a tandem mass tag method. A total of 248 DEPs, including 98 upregulated and 150 downregulated proteins, were identified between AL and non-AL groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that DEPs were enriched in neutrophil degranulation, bacterial infection, proteolysis, hemostasis, and complement and coagulation cascades. The results of enzyme-linked immunosorbent assay validated that the expression of the top three upregulated DEPs, AMY2A, RETN, and CELA3A, was significantly increased in the drainage fluid of AL patients, compared with that of non-AL patients (AMY2A, P = 0.001; RETN, P < 0.0001; and CELA3A, P = 0.023). Thus, our findings provide several potential biomarkers for the early diagnosis of AL after rectal cancer resection.

Efficacy and safety of metformin in combination with chemotherapy in cancer patients without diabetes: systematic review and meta-analysis.

Background: The results of a meta-analysis of retrospective studies suggest that the use of metformin in cancer patients may prolong progression-free disease survival and overall survival. However, the studies included in the meta-analysis did not strictly distinguish between patients with or without type 2 diabetes mellitus. Therefore, further studies are needed to assess whether the use of adjuvant chemotherapy with metformin in cancer patients without diabetes improves prognosis. Method: Systematic searches of Embase, Pubmed, and The Cochrane library were performed for the subject terms metformin and neoplasm and for free words. Data related to PFS, OS were extracted according to inclusion exclusion criteria. The data were combined and meta-analysis was performed using Review Manager 5.4 to confirm the efficacy and safety of metformin administration. Results: There were 3228 publications retrieved from the database and a total of 13 publications with 955 patients were included in the meta-analysis after screening. All included studies were randomised controlled trials. Metformin combined with adjuvant chemotherapy did not improve progression-free survival (HR=1,95CI 0.79-1.25), overall survival (HR=0.91,95% CI 0.69-1.20) and did not improve objective disease response rates in patients. There was no significant difference in grade 3-4 adverse reactions compared to placebo. Conclusion: In this meta-analysis of randomised controlled trial studies, we found that chemotherapy in combination with metformin in cancer patients without diabetes did not prolong progression-free survival and overall survival and improved disease control in patients, although there was no significant difference in terms of safety. More high-quality randomised controlled trials are needed in the future to confirm the in vivo anti-tumour activity and survival benefit of metformin.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: • The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. • The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. • The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.

Bergenin ameliorates diabetic nephropathy in C57BL/6 J mice by TLR4/MyD88/NF-κB signalling pathway regulation.

Bergenin (BG) is a polyphenolic substance which has therapeutic potential in the treatment of diabetic nephropathy (DN), a common complication of type II diabetes. However, the mechanisms underlying these effects remain unclear. We studied the protective effects and mechanisms of BG in DN mice, focusing on the TLR4/MyD88/NF-κB signalling pathway. C57BL/6 J mice were used as experiments (n=60), and 10 animals were randomly selected as normal control. The DN model was developed by administering an intraperitoneal injection of streptozotocin (40 mg/kg BW for three days) and a high-fat diet (n=50). BG (20, 40, and 80 mg/kg BW, once a day) was administered orally for four weeks. After BG treatment, the food and water intake of DN mice decreased, blood glucose levels decreased, and insulin resistance reduced. As a result, serum LDL-C, TC, and TG levels decreased; HDL-C levels increased; SOD, CAT, and GSH-Px levels decreased; and MDA levels increased. BG administration reduced AST, ALT, BUN, and CRE levels and inflammatory factors (including TNF-α, MCP-1, IL-1ß, and IL-6). Histopathology revealed a significant improvement in pathological damage to the liver, kidney, and spleen of mice treated with BG, and TLR4, MyD88, and NF-κB p65 were down-regulated at both mRNA and protein levels in the BG-treated group. Based on these results, BG therapeutic type II DN by hypoglycaemia, improving liver and kidney function, and anti-oxidative stress; reducing inflammation; and inhibiting the TLR4/MyD88/NF-κB signalling pathway. The results of this study suggest that BG can be used as an effective treatment for type II DN.

Three-dimensional convolutional neural network model to identify clinically significant prostate cancer in transrectal ultrasound videos: a prospective, multi-institutional, diagnostic study.

Background: Identifying patients with clinically significant prostate cancer (csPCa) before biopsy helps reduce unnecessary biopsies and improve patient prognosis. The diagnostic performance of traditional transrectal ultrasound (TRUS) for csPCa is relatively limited. This study was aimed to develop a high-performance convolutional neural network (CNN) model (P-Net) based on a TRUS video of the entire prostate and investigate its efficacy in identifying csPCa. Methods: Between January 2021 and December 2022, this study prospectively evaluated 832 patients from four centres who underwent prostate biopsy and/or radical prostatectomy. All patients had a standardised TRUS video of the whole prostate. A two-dimensional CNN (2D P-Net) and three-dimensional CNN (3D P-Net) were constructed using the training cohort (559 patients) and tested on the internal validation cohort (140 patients) as well as on the external validation cohort (133 patients). The performance of 2D P-Net and 3D P-Net in predicting csPCa was assessed in terms of the area under the receiver operating characteristic curve (AUC), biopsy rate, and unnecessary biopsy rate, and compared with the TRUS 5-point Likert score system as well as multiparametric magnetic resonance imaging (mp-MRI) prostate imaging reporting and data system (PI-RADS) v2.1. Decision curve analyses (DCAs) were used to determine the net benefits associated with their use. The study is registered at https://www.chictr.org.cn with the unique identifier ChiCTR2200064545. Findings: The diagnostic performance of 3D P-Net (AUC: 0.85-0.89) was superior to TRUS 5-point Likert score system (AUC: 0.71-0.78, P = 0.003-0.040), and similar to mp-MRI PI-RADS v2.1 score system interpreted by experienced radiologists (AUC: 0.83-0.86, P = 0.460-0.732) and 2D P-Net (AUC: 0.79-0.86, P = 0.066-0.678) in the internal and external validation cohorts. The biopsy rate decreased from 40.3% (TRUS 5-point Likert score system) and 47.6% (mp-MRI PI-RADS v2.1 score system) to 35.5% (2D P-Net) and 34.0% (3D P-Net). The unnecessary biopsy rate decreased from 38.1% (TRUS 5-point Likert score system) and 35.2% (mp-MRI PI-RADS v2.1 score system) to 32.0% (2D P-Net) and 25.8% (3D P-Net). 3D P-Net yielded the highest net benefit according to the DCAs. Interpretation: 3D P-Net based on a prostate grayscale TRUS video achieved satisfactory performance in identifying csPCa and potentially reducing unnecessary biopsies. More studies to determine how AI models better integrate into routine practice and randomized controlled trials to show the values of these models in real clinical applications are warranted. Funding: The National Natural Science Foundation of China (Grants 82202174 and 82202153), the Science and Technology Commission of Shanghai Municipality (Grants 18441905500 and 19DZ2251100), Shanghai Municipal Health Commission (Grants 2019LJ21 and SHSLCZDZK03502), Shanghai Science and Technology Innovation Action Plan (21Y11911200), and Fundamental Research Funds for the Central Universities (ZD-11-202151), Scientific Research and Development Fund of Zhongshan Hospital of Fudan University (Grant 2022ZSQD07).

Effect of resveratrol in gestational diabetes mellitus and its complications.

The incidence rate of diabetes in pregnancy is about 20%, and diabetes in pregnancy will have a long-term impact on the metabolic health of mothers and their offspring. Mothers may have elevated blood glucose, which may lead to blood pressure disease, kidney disease, decreased resistance and secondary infection during pregnancy. The offspring may suffer from abnormal embryonic development, intrauterine growth restriction, obesity, autism, and other adverse consequences. Resveratrol (RSV) is a natural polyphenol compound, which is found in more than 70 plant species and their products, such as Polygonum cuspidatum, seeds of grapes, peanuts, blueberries, bilberries, and cranberries. Previous studies have shown that RSV has a potential beneficial effect on complex pregnancy, including improving the indicators of diabetes and pregnancy diabetes syndrome. This article has reviewed the molecular targets and signaling pathways of RSV, including AMP-activated protein kinase, mitogen-activated protein kinases, silent information regulator sirtuin 1, miR-23a-3p, reactive oxygen species, potassium channels and CX3C chemokine ligand 1, and the effect of RSV on gestational diabetes mellitus (GDM) and its complications. RSV improves the indicators of GDM by improving glucose metabolism and insulin tolerance, regulating blood lipids and plasma adipokines, and modulating embryonic oxidative stress and apoptosis. Furthermore, RSV can ameliorate the GDM complications by reducing oxidative stress, reducing the effects on placentation, reducing the adverse effects on embryonic development, reducing offspring's healthy risk, and so on. Thus, this review is of great significance for providing more options and possibilities for further research on medication of gestational diabetes.

Imaging characteristics and treatment strategies of traumatic diaphragmatic hernia with aortic dissection: a report of 3 cases.

BACKGROUND: Traumatic aortic dissection with traumatic diaphragmatic hernia is a rare traumatic disease. The purpose of this article is to investigate the imaging characteristics and treatment strategies for traumatic diaphragmatic hernia with aortic dissection. CASE PRESENTATION: The imaging and clinical data of 3 patients with traumatic diaphragmatic hernia combined with aortic dissection were analyzed retrospectively. Of the three cases, two were males, and one was female; their mean age was 52.7 years (range, 47-62 years). Plain chest CT scans revealed diaphragmatic hernia in 2 patients, but no traumatic aortic dissection was found. Diaphragmatic hernia repair was performed in all patients. Aortic dilatation was found during intraoperative exploration, and aortic dissection was confirmed by postoperative enhanced CT. One patient underwent stent implantation and recovered smoothly (Case 1). The other patient refused stent implantation and died of thoracic hemorrhage (Case 2). The third patient underwent preoperative enhanced CT to identify traumatic diaphragmatic hernia with aortic dissection (Case 3). Aortic covered stent implantation was performed immediately, and diaphragmatic hernia repair was performed at a selected time. The patient's postoperative recovery was good. CONCLUSION: A preoperative plain chest CT scan indicated diaphragmatic hernia in major blunt thoracic trauma patients with a history of trauma and blurred periaortic spaces accompanied by hematocele and other imaging manifestations. Chest-enhanced CT should be performed to improve the diagnostic accuracy of aortic dissection.

A two-dimensional analytical model for heavy metal contaminants transport in permeable reactive barrier.

Permeable reactive barrier (PRB) remediation technology has been widely used in the remediation of groundwater contamination. In numerical simulations, neglecting the non-uniform distribution of heavy metal contamination along the depth may lead to deviations between simulation results and reality. The distribution of heavy metals in the soil layer around a non-ferrous mining area in Hezhou, Guangxi, southern China was investigated, and it was found that the standard Gaussian function could well describe the non-uniform distribution of heavy metals in the soil layer. A two-dimensional analytical model solved by the finite element method was used to simulate the migration process of heavy metal contamination in the aquifer and PRB. The results show that the uniform distribution of contaminants along the depth ignores the dilution effect, which may underestimate the service life of the PRB and lead to an overly conservative design of the PRB. The breakthrough time of the PRB decreases with the increase of the maximum initial concentration (Cin,max) and the high concentration range (σ), and increases almost linearly with the barrier thickness (Lw). An optimal design method for PRB location and thickness is proposed, which can provide a reference for the engineering application of PRB.