IFI16 promotes the progression of clear cell renal cell carcinoma through the IL6/PI3K/AKT axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. METHODS: We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. RESULTS: IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). CONCLUSION: IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.

Disulfidptosis-Related LncRNA Signatures for Prognostic Prediction in Kidney Renal Clear Cell Carcinoma.

INTRODUCTION BACKGROUND: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC. MATERIALS AND METHODS: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model. RESULTS: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints. CONCLUSION: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC.

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

Short-term variation of the fetal heart rate as a marker of intraamniotic infection in pregnancies with preterm prelabor rupture of membranes: a historical cohort study.

INTRODUCTION: Intraamniotic infection (IAI) and subsequent early-onset neonatal sepsis (EONS) are among the main complications associated with preterm prelabor rupture of membranes (PPROM). Currently used diagnostic tools have been shown to have poor diagnostic performance for IAI. This study aimed to investigate whether the exposure to IAI before delivery is associated with short-term variation of the fetal heart rate in pregnancies with PPROM. METHODS: Observational cohort study of 678 pregnancies with PPROM, delivering between 24 + 0 and 33 + 6 gestational weeks from 2012 to 2019 in five labor units in Stockholm County, Sweden. Electronic medical records were examined to obtain background and exposure data. For the exposure IAI, we used the later diagnosis of EONS in the offspring as a proxy. EONS is strongly associated to IAI and was considered a better proxy for IAI than the histological diagnosis of acute chorioamnionitis, since acute chorioamnionitis can be observed in the absence of both positive microbiology and biochemical markers for inflammation. Cardiotocography traces were analyzed by a computerized algorithm for short-term variation of the fetal heart rate, which was the main outcome measure. RESULTS: Twenty-seven pregnancies were categorized as having an IAI, based on the proxy diagnosis of EONS after birth. Fetuses exposed to IAI had significantly lower short-term variation values in the last cardiotocography trace before birth than fetuses who were not exposed (5.25 vs 6.62 ms; unadjusted difference: -1.37, p = 0.009). After adjustment for smoking and diabetes, this difference remained significant. IAI with a later positive blood culture in the neonate (n = 12) showed an even larger absolute difference in STV (-1.65; p = 0.034), with a relative decrease of 23.5%. CONCLUSION: In pregnancies with PPROM, fetuses exposed to IAI with EONS as a proxy have lower short-term variation of the fetal heart rate than fetuses who are not exposed. Short-term variation might be useful as adjunct surveillance in pregnancies with PPROM.

Development and validation of a prognostic nomogram for 3-year all-cause mortality risk among elderly patients undergoing surgery for osteoporotic fractures.

Introduction: To develop and validate a comprehensive prognostic model for the mid-to-long term mortality risk among ≥50-year-old osteoporotic fracture (OPF) surgical patients. Methods: Our retrospective investigation included data from the Osteoporotic Fracture Registration System established by the Affiliated Kunshan Hospital of Jiangsu University, and involved 1,656 patients in the development set and 675 patients in the validation set. Subsequently, we employed a multivariable Cox regression model to establish a 3-year mortality predicting nomogram, and the model performance was further evaluated using C-index and calibration plots. Decision curve analysis (DCA) was employed to assess feasibility of the clinical application of this model. Results: Using six prognostic indexes, namely, patient age, gender, the American Society of Anesthesiologists (ASA) score, the Charlson comorbidity index (CCI), fracture site, and fracture liaison service (FLS), we generated a simple nomogram. The nomogram demonstrated satisfactory discrimination within the development (C-index = 0.8416) and validation (C-index = 0.8084) sets. Using calibration plots, we also revealed good calibration. The model successfully classified patients into different risk categories and the results were comparable in both the development and validation sets. Finally, a 1-70% probability threshold, according to DCA, suggested that the model has promise in clinical settings. Conclusion: Herein, we offer a robust tool to estimating the 3-year all-cause mortality risk among elderly OPF surgical patients. However, we recommend further assessments of the proposed model prior to widespread clinical implementation.

CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer.

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.

Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.

A novel fracture liaison service using digital health: impact on mortality in hospitalized elderly osteoporotic fracture patients.

We examined the performance of an intelligent fracture liaison service (FLS) assisted by digital health (DH) to reduce all-cause mortality (ACM) risk. According to our findings, the new FLS reduced ACM by 36%. INTRODUCTION: A well-designed secondary prevention program known as FLS enhances the bone densitometry-based assessment rate as well as osteoporosis (OP) medication usage following a fracture. However, there are only a few reports on FLS incorporating DH, and it remains unclear whether this integration has influenced patient ACM, which refers to the overall death rate from any cause during the study period. METHODS: This retrospective observational study was conducted on data from the Fragility Fracture Registration System database linked to the Regional Health Registration Platform of Kunshan City and the Population Death Registration System of Jiangsu Province for one tertiary-level A hospital in China. Patients aged ≥ 50 years, who experienced an OP fracture between January 1, 2017, and July 27, 2022, requiring hospitalization, were selected for analysis. We compared the outcomes of patients who received routine fragility fracture management (the no-FLS group) or FLS (the FLS group). We employed multivariable Cox regression with inverse probability weighting based on the propensity score (PS). RESULTS: Of 2317 patients, 756 (32.6%) received FLS and 1561 (67.4%) did not. Using PS matching, we minimized the baseline characteristic differences between the two groups in the propensity score-matched samples, relative to the unmatched samples. Based on our analysis, the new FLS reduced ACM by 36% (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; P-value = 0.004). Moreover, FLS patients experienced further reductions in fall-related mortality, refracture rate, and total refracture-related hospital costs, and had increased dual-energy X-ray absorptiometry (DXA) testing and treatment initiation rates, relative to the no-FLS patients. CONCLUSIONS: A new FLS model implementation assisted by DH can effectively reduce ACM among elderly patients with OP fractures requiring surgery. In future investigations, we recommend examining the scalability of this model.

Bidirectional Confined Redox Catalysis Manipulated Quasi-Solid Iodine Conversion for Shuttle-Free Solid-State Zn-I2 Battery.

Electrochemically reversible conversion of I2/I- redox couple in a controllable iodine speciation manner is the eternal target for practical metal-iodine batteries. This contribution demonstrates an advanced polyiodide-free Zn-I2 battery achieved by the bidirectional confined redox catalysis-directed quasi-solid iodine conversion. A core-shell structured iodine cathode is fabricated by integrating multiporous Prussian blue nanocubes as a catalytic mediator, and the polypyrrole sheath afforded a confinement environment that favored the iodine redox. The zincate Znx+1FeIII/II[Fe(CN)6]y has substantially faster zinc-ion intercalation kinetics and overlapping kinetic voltage profiles compared with the I2/ZnI2 redox, and behave as a redox mediator that catalyze reduction of polyiodides via chemical redox reactions during battery discharging and an exemplary reaction is Zn(I3)2+2Znx+1FeII[Fe(CN)6]y=3ZnI2+2ZnxFeIII[Fe(CN)6]y,ΔG=-19.3 kJ mol-1). During the following recharging process, the electrodeposited ZnI2 can be facially activated by iron redox hotspots, and the ZnxFe[FeIII/II(CN)6]y served as a cation-transfer mediator and spontaneously catalyze polyiodides oxidation (Zn(I3)2+2ZnxFe[FeIII(CN)6]y=3I2+2Znx+1Fe[FeII(CN)6]y,ΔG = -7.72 kJ mol-1), manipulating the reversible one-step conversion of ZnI2 back to I2. Accordingly, a flexible solid-state battery employing the designed cathode can deliver an energy density of 215 Wh kgiodine -1.

Analysis of the Risk Factors for Massive Hemorrhage after PCNL in the Oblique Supine Position.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is a proven and efficient treatment method; Nevertheless, it is essential to note that there is still a risk of significant bleeding. The purpose of this paper is to explore the risk factors for massive hemorrhage after PCNL in the oblique supine position and provide a basis for the development of measures to prevent massive hemorrhage. METHODS: The clinical data of 97 patients who underwent PCNL in the oblique supine position at Changshu No. 2 People's Hospital from January 2019 to December 2020 were retrospectively analyzed. Patients were placed in the massive hemorrhage group if their hemoglobin levels decreased by ≥20 g/L 24 h after the operation, and the other patients were placed in the nonmassive hemorrhage group. Differences in sex, age, body mass index (BMI), hypertension, diabetes, surgical side, perirenal fat stranding (PFS), calculus long diameter, surgical access, and operation time were compared between the two groups to determine the risk factors for massive bleeding. Multivariable logistic regression analysis was used to determine the risk factors for massive hemorrhage after PCNL. RESULTS: There were no significant differences in sex, BMI, hypertension, diabetes, surgical side, or calculus long diameter between the two groups (p > 0.05), and there were statistically significant differences in age, PFS, surgical access, and operation time (p < 0.05). Multivariate logistic regression analysis indicated that PFS and extensive surgical access were independent risk factors (p < 0.05). CONCLUSIONS: PFS and extensive surgical access were independent risk factors. Carefully reading computed tomography (CT) films before surgery and reducing the size of the surgical access area are important measures for reducing the risk of massive hemorrhages.

Multiple cullin-associated E3 ligases regulate cyclin D1 protein stability.

Cyclin D1 is a key regulator of cell cycle progression, which forms a complex with CDK4/6 to regulate G1/S transition during cell cycle progression. Cyclin D1 has been recognized as an oncogene since it was upregulated in several different types of cancers. It is known that the post-translational regulation of cyclin D1 is controlled by ubiquitination/proteasome degradation system in a phosphorylation-dependent manner. Several cullin-associated F-box E3 ligases have been shown to regulate cyclin D1 degradation; however, it is not known if additional cullin-associated E3 ligases participate in the regulation of cyclin D1 protein stability. In this study, we have screened an siRNA library containing siRNAs specific for 154 ligase subunits, including F-box, SOCS, BTB-containing proteins, and DDB proteins. We found that multiple cullin-associated E3 ligases regulate cyclin D1 activity, including Keap1, DDB2, and WSB2. We found that these E3 ligases interact with cyclin D1, regulate cyclin D1 ubiquitination and proteasome degradation in a phosphorylation-dependent manner. These E3 ligases also control cell cycle progression and cell proliferation through regulation of cyclin D1 protein stability. Our study provides novel insights into the regulatory mechanisms of cyclin D1 protein stability and function.

Time - sensitive effects of Zhuang medicated thread moxibustion on estrogen level in female perimenopausal model rats / Efectos sensibles al tiempo de la moxibustión con hilo medicado de Zhuang sobre el nivel de estrógeno en ratas modelo perimenopáusicas hembras

The present study was conducted to ascertain the estrogenic effect of Zhuang Medicated Thread Moxibustion (ZMTM) and explore its time - sensitive impact on estradiol (E2) in female perimenopausal rats. 40 female rats were randomized into four gr oups: the control, model, ZMTM, and acupuncture groups. The perimenopausal syndrome was induced in the last three groups with a daily subcutaneous dose of 80 mg/kg of 4 - vinylcyclohexene diepoxide for 15 days. Afterward, rats in the model and control group s were fed routinely, while rats in the ZMTM and acupuncture groups were treated with six ZMTM and acupuncture courses, respectively. Results of the study suggested that following the six courses of treatment, the E2 level in the model group was significan tly the lowest, while the regular group was the highest (P < 0.05). There was also a gradual increase in the E2 level of the ZMTM group compared to the model and acupuncture groups, e.g. after the 5th and 6th courses of treatment, their E2 level was signif icantly higher than the model and acupuncture groups. The ZMTM group was better than the model and acupuncture groups. In summary, ZMTM can improve perimenopausal induced rats' estrogen level.

El presen te estudio se llevó a cabo para determinar el efecto estrogénico de la moxibustión con hilo medicado Zhuang (ZMTM) y explorar su impacto sensible al tiempo en el estradiol (E2) en ratas hembras perimenopáusicas. Se dividió al azar una muestra de 40 ratas h embras en cuatro grupos: control, modelo, ZMTM y acupuntura. El síndrome perimenopáusico se indujo en los últimos tres grupos con una dosis subcutánea diaria de 80 mg/kg de diepóxido de 4 - vinilciclohexeno durante 15 días. Después, las ratas en los grupos m odelo y control fueron alimentadas rutinariamente, mientras que las ratas en los grupos ZMTM y acupuntura recibieron seis cursos de ZMTM y acupuntura, respectivamente. Los resultados del estudio sugieren que después de los seis cursos de tratamiento, el ni vel de E2 en el grupo modelo fue significativamente más bajo, mientras que el grupo regular fue más alto ( p < 0,05). También hubo un aumento gradual en el nivel de E2 del grupo ZMTM en comparación con los grupos modelo y acupuntura, por ejemplo, desp ués del quinto y sexto cursos de tratamiento, su nivel de E2 fue significativamente más alto que los grupos modelo y acupuntura. El grupo ZMTM fue mejor que los grupos modelo y acupuntura. En resumen, el ZMTM puede mejorar el nivel de estrógeno de las rata s inducidas por la perimenopausia.

Novel COL4A3 synonymous mutation causes Alport syndrome coexistent with immunoglobulin A nephropathy in a woman: A case report.

BACKGROUND: Alport syndrome (AS) is an inherited disease of the glomerular basement membrane caused by mutations in genes encoding α3, α4, or α5 chains of type IV collagen. It manifests with hematuria or proteinuria, which is often accompanied by hearing impairments and ocular abnormalities. Histopathologically, AS shows mesangial proliferation and sometimes incidental immunoglobulin A (IgA) deposition. Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features. CASE SUMMARY: Herein, we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for > 2 years. This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS (ADAS) and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing, which suggested that the patient carried a novel heterozygous variation (c.888G>A:p.Gln296Gln) in the COL4A3 gene that enriches the mutation spectrum of ADAS. The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established. After one year of therapy, a significant reduction in proteinuria was observed. The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels. Renal function also maintained well during the follow-up. CONCLUSION: Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.

Association of 25-hydroxyvitamin D levels with lipid profiles in osteoporosis patients: a retrospective cross-sectional study.

BACKGROUND: In the literature, scarce data investigate the link between 25-hydroxyvitamin D (25[OH]D) and blood lipids in the osteoporosis (OP) population. 25(OH)D, as a calcium-regulating hormone, can inhibit the rise of parathyroid hormone, increase bone mineralization to prevent bone loss, enhance muscle strength, improve balance, and prevent falls in the elderly. This retrospective cross-sectional study aimed to investigate the association between serum 25(OH)D levels and lipid profiles in patients with osteoporosis, with the objective of providing insight for appropriate vitamin D supplementation in clinical settings to potentially reduce the incidence of cardiovascular disease, which is known to be a major health concern for individuals with osteoporosis. METHODS: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, including 2063 OP patients who received biochemical blood analysis of lipids during hospitalization from January 2015 to March 2022. The associations between serum lipids and 25(OH)D levels were examined by multiple linear regression. The dependent variables in the analysis were the concentrations of serum lipoprotein, total cholesterol (TC), triglycerides (TGs), apolipoprotein-A, lipoprotein A, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C). The independent variable was the concentration of blood serum 25(OH)D. At the same time, age, body mass index, sex, time and year of serum analysis, primary diagnosis, hypertension, diabetes, statins usage, beta-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide were covariates. Blood samples were collected in the early morning after the overnight fasting and were analyzed using an automated electrochemiluminescence immunoassay on the LABOSPECT 008AS platform (Hitachi Hi-Tech Co., Ltd., Tokyo, Japan). The generalized additive model was further applied for nonlinear associations. The inception result for smoothing the curve was evaluated by two-piecewise linear regression exemplary. RESULTS: Our results proved that in the OP patients, the serum 25(OH)D levels were inversely connected with blood TGs concentration, whereas they were positively associated with the HDL, apolipoprotein-A, and lipoprotein A levels. In the meantime, this research also found a nonlinear relationship and threshold effect between serum 25(OH)D and TC, LDL-C. Furthermore, there were positive correlations between the blood serum 25(OH)D levels and the levels of TC and LDL-C when 25(OH)D concentrations ranged from 0 to 10.04 ng/mL. However, this relationship was not present when 25(OH)D levels were higher than 10.04 ng/mL. CONCLUSIONS: Our results demonstrated an independent relationship between blood lipids and vitamin D levels in osteoporosis patients. While we cannot establish a causal relationship between the two, our findings suggest that vitamin D may have beneficial effects on both bone health and blood lipid levels, providing a reference for improved protection against cardiovascular disease in this population. Further research, particularly interventional studies, is needed to confirm these associations and investigate their underlying mechanisms.

Deep learning and ultrasound feature fusion model predicts the malignancy of complex cystic and solid breast nodules with color Doppler images.

This study aimed to evaluate the performance of traditional-deep learning combination model based on Doppler ultrasound for diagnosing malignant complex cystic and solid breast nodules. A conventional statistical prediction model based on the ultrasound features and basic clinical information was established. A deep learning prediction model was used to train the training group images and derive the deep learning prediction model. The two models were validated, and their accuracy rates were compared using the data and images of the test group, respectively. A logistic regression method was used to combine the two models to derive a combination diagnostic model and validate it in the test group. The diagnostic performance of each model was represented by the receiver operating characteristic curve and the area under the curve. In the test cohort, the diagnostic efficacy of the deep learning model was better than traditional statistical model, and the combined diagnostic model was better and outperformed the other two models (combination model vs traditional statistical model: AUC: 0.95 > 0.70, P = 0.001; combination model vs deep learning model: AUC: 0.95 > 0.87, P = 0.04). A combination model based on deep learning and ultrasound features has good diagnostic value.

Predictive Model for the Diagnosis of Benign/Malignant Complex Cystic and Solid Breast Nodules.

PURPOSE: To develop an ultrasound predictive model to differentiate between benign and malignant complex cystic and solid nodules (C-SNs). METHODS: A total of 211 patients with complex C-SNs rated as American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) category 4 or 5 on the ultrasound reports were included in the study, from June 2018-2021. Multivariate stepwise logistic regression analysis was used to establish a predictive model, based on clinical and ultrasound features. The diagnostic performance of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A total of 109 breast nodules, including 74 benign nodules (67.89%) and 35 malignant nodules (32.11%), were detected by surgical pathology or puncture biopsy. Multivariate analysis showed that the blood flow (BF) of complex C-SNs (p = 0.03), cystic fluid transmission (p = 0.02), longitudinal diameter (p < 0.001), and age (p = 0.03) were independent risk factors for malignant complex cystic and solid breast nodules. The ultrasound model equation was Z=-12.14+2.24×X12+1.97×X20+0.40×X7+0.11×X0; M=ez1+ez (M is the malignancy score, e = 2.72). The area under the curve (AUC) was 0.89, which indicated good predictive utility for the model. CONCLUSIONS: A prediction model incorporating major risk factors can predict the malignant C-SNs with accuracy.

Systematic review and meta-analysis of completely retroperitoneoscopic nephroureterectomy versus traditional retroperitoneoscopic nephroureterectomy in upper tract urothelial carcinoma.

BACKGROUND: This systematic review and meta-analysis aim to evaluate the efficacy and safety of completely retroperitoneoscopic nephroureterectomy (CRNU) for the treatment of upper urinary tract urothelial carcinoma (UTUC). METHODS: A systematic review of PubMed and Web of Science databases was conducted to identify trials comparing the outcomes of CRNU and other surgical procedures. A total of 6 case-control studies were selected for analysis. The efficacy and safety of CRNU were evaluated using mean difference or hazard ratio (HR) with 95% CIs, employing continuous or dichotomous method with a random or fixed-effect model. Meta-analysis was performed using STATA 11.0 software. RESULTS: The meta-analysis indicated that CRNU in subjects with UTUC was significantly associated with a shorter operation time (standardized mean difference, -1.36; 95% CI, -1.61 to -1.11, P < .001) and lower blood loss (standardized mean difference, -0.54; 95% CI, -0.77 to -0.31, P < .001) when compared to traditionally retroperitoneoscopic nephroureterectomy (TRNU). No significant difference was observed in the occurrence of grade I & II complications (HR, 1.04; 95% CI, 0.49-2.2, P = .915) and total complications (HR, 0.69; 95% CI, 0.38-1.27, P = .238) between CRNU and TRNU. CONCLUSION: The findings suggest that CRNU is an advanced surgical technique that is safe and effective for the treatment of UTUC. We recommend that CRNU be further employed for patients with UTUC. Further randomized, multicenter trials are needed to validate these results, given the limitations of this study.

Japanese medaka Olpax6.1 mutant as a potential model for spondylo-ocular syndrome.

pax6 is a canonic master gene for eye formation. Knockout of pax6 affects the development of craniofacial skeleton and eye in mice. Whether pax6 affects the development of spinal bone has not been reported yet. In the present study, we used CRISPR/Cas9 system to generate Olpax6.1 mutant in Japanese medaka. Phenotype analysis showed that ocular mutation caused by the Olpax6.1 mutation occurred in the homozygous mutant. The phenotype of heterozygotes is not significantly different from that of wild-type. In addition, knockout Olpax6.1 resulted in severe curvature of the spine in the homozygous F2 generation. Comparative transcriptome analysis and qRT-PCR revealed that the defective Olpax6.1 protein caused a decrease in the expression level of sp7, col10a1a, and bglap, while the expression level of xylt2 did not change significantly. The functional enrichment of differentially expressed genes (DEGs) using the Kyoto Encyclopedia of Genes and Genomes database showed that the DEGs between Olpax6.1 mutation and wild-type were enriched in p53 signaling pathway, extracellular matrix (ECM) -receptor interaction, et al. Our results indicated that the defective Olpax6.1 protein results in the reduction of sp7 expression level and the activation of p53 signaling pathway, which leads to a decrease in the expression of genes encoding ECM protein, such as collagen protein family and bone gamma-carboxyglutamate protein, which further inhibits bone development. Based on the phenotype and molecular mechanism of ocular mutation and spinal curvature induced by Olpax6.1 knockout, we believe that the Olpax6.1-/- mutant could be a potential model for the study of spondylo-ocular syndrome.