Proteomics analysis of deep fascia in acute compartment syndrome.

Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS.

Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

Fragment distance-guided dual-stream learning for automatic pelvic fracture segmentation.

Pelvic fracture is a complex and severe injury. Accurate diagnosis and treatment planning require the segmentation of the pelvic structure and the fractured fragments from preoperative CT scans. However, this segmentation is a challenging task, as the fragments from a pelvic fracture typically exhibit considerable variability and irregularity in the morphologies, locations, and quantities. In this study, we propose a novel dual-stream learning framework for the automatic segmentation and category labeling of pelvic fractures. Our method uniquely identifies pelvic fracture fragments in various quantities and locations using a dual-branch architecture that leverages distance learning from bone fragments. Moreover, we develop a multi-size feature fusion module that adaptively aggregates features from diverse receptive fields tailored to targets of different sizes and shapes, thus boosting segmentation performance. Extensive experiments on three pelvic fracture datasets from different medical centers demonstrated the accuracy and generalizability of the proposed method. It achieves a mean Dice coefficient and mean Sensitivity of 0.935±0.068 and 0.929±0.058 in the dataset FracCLINIC, and 0.955±0.072 and 0.912±0.125 in the dataset FracSegData, which are superior than other comparing methods. Our method optimizes the process of pelvic fracture segmentation, potentially serving as an effective tool for preoperative planning in the clinical management of pelvic fractures.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Video-based Soft Tissue Deformation Tracking for Laparoscopic Augmented Reality-based Navigation in Kidney Surgery.

Minimally invasive surgery (MIS) remains technically demanding due to the difficulty of tracking hidden critical structures within the moving anatomy of the patient. In this study, we propose a soft tissue deformation tracking augmented reality (AR) navigation pipeline for laparoscopic surgery of the kidneys. The proposed navigation pipeline addresses two main sub-problems: the initial registration and deformation tracking. Our method utilizes preoperative MR or CT data and binocular laparoscopes without any additional interventional hardware. The initial registration is resolved through a probabilistic rigid registration algorithm and elastic compensation based on dense point cloud reconstruction. For deformation tracking, the sparse feature point displacement vector field continuously provides temporal boundary conditions for the biomechanical model. To enhance the accuracy of the displacement vector field, a novel feature points selection strategy based on deep learning is proposed. Moreover, an ex-vivo experimental method for internal structures error assessment is presented. The ex-vivo experiments indicate an external surface reprojection error of 4.07 ± 2.17mm and a maximum mean absolutely error for internal structures of 2.98mm. In-vivo experiments indicate mean absolutely error of 3.28 ± 0.40mm and 1.90±0.24mm, respectively. The combined qualitative and quantitative findings indicated the potential of our AR-assisted navigation system in improving the clinical application of laparoscopic kidney surgery.

Influence of COVID-19 infection on early pregnancy outcomes in different periods around frozen embryo transfer.

PURPOSE: The study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET. METHODS: A retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days, < 60 days before FET, 0-14 days, 15-28 days, and 29-70 days after FET. Clinical outcomes were compared across these groups. RESULTS: The infection rate among the total of 709 cases was 78.28%. Infected individuals exhibited either asymptomatic or mild symptoms. The ongoing pregnancy rates for the first four groups were 40.7%, 44.4%, 40.5%, and 34.2% (P = 0.709) respectively, biochemical pregnancy rates (59.1% vs. 61.1% vs. 67.6% vs. 55.7%, P = 0.471) and clinical pregnancy rates (49.6% vs. 55.6% vs. 55.4% vs. 48.1%, P = 0.749), all showed no significant differences. Early spontaneous abortion rates across all six groups were 18.3%, 20.0%, 25.0%, 28.9%, 5.4%, and 19.0% respectively, with no significant differences (P = 0.113). Multivariable logistic analysis revealed no significant correlation between the infection and ongoing pregnancy. CONCLUSION: Asymptomatic or mild COVID-19 infections occurring around FET do not appear to have a significant adverse impact on early pregnancy outcomes.

Evaluation of spine disorders using high contrast imaging of the cartilaginous endplate.

Introduction: Many spine disorders are caused by disc degeneration or endplate defects. Because nutrients entering the avascular disc are channeled through the cartilaginous endplate (CEP), structural and compositional changes in the CEP may block this solute channel, thereby hindering disc cell function. Therefore, imaging the CEP region is important to improve the diagnostic accuracy of spine disorders. Methods: A clinically available T1-weighted and fat-suppressed spoiled gradient recalled-echo (FS-SPGR) sequence was optimized for high-contrast CEP imaging, which utilizes the short T1 property of the CEP. The FS-SPGR scans with and without breath-hold were performed for comparison on healthy subjects. Then, the FS-SPGR sequence which produced optimal image quality was employed for patient scans. In this study, seven asymptomatic volunteers and eight patients with lower back pain were recruited and scanned on a 3T whole-body MRI scanner. Clinical T2-weighted fast spin-echo (T2w-FSE) and T1-weighted FSE (T1w-FSE) sequences were also scanned for comparison. Results: For the asymptomatic volunteers, the FS-SPGR scans under free breathing conditions with NEX = 4 showed much higher contrast-to-noise ratio values between the CEP and bone marrow fat (BMF) (CNRCEP-BMF) (i.e., 7.8 ± 1.6) and between the CEP and nucleus pulposus (NP) (CNRCEP-NP) (i.e., 6.1 ± 1.2) compared to free breathing with NEX = 1 (CNRCEP-BMF: 4.0 ± 1.1 and CNRCEP-NP: 2.5 ± 0.9) and breath-hold condition with NEX = 1 (CNRCEP-BMF: 4.2 ± 1.3 and CNRCEP-NP: 2.8 ± 1.3). The CEP regions showed bright linear signals with high contrast in the T1-weighted FS-SPGR images in the controls, while irregularities of the CEP were found in the patients. Discussion: We have developed a T1-weighted 3D FS-SPGR sequence to image the CEP that is readily translatable to clinical settings. The proposed sequence can be used to highlight the CEP region and shows promise for the detection of intervertebral disc abnormalities.

Production of Coal Fines in Deep Coal Seam via Morphologic, Flow-Channel, Mineral Analyses: Evidence from Coalbed Methane Wells in the Qinshui Basin.

During the development of deep coalbed methane (CBM), the production of coal fines is common and suppresses the yield of CBM. This work takes the deep CBM wells in the Qinshui Basin as a case study, and the output, composition, morphology, and sources of coal fines were investigated through scanning electron microscopy, X-ray diffraction, proximate analysis, and particle size measurement including image analysis, laser diffraction, and dynamic light scattering. The results indicate that, in comparison with shallow CBM wells, deep wells produce a greater quantity of coal fines which are darker in color and have smaller particle sizes, with the majority being less than 10 µm. The coal fines exist predominantly as aggregates that contained the iron-bearing and clay minerals. Based on the Liddinger particle settling model, the water production volume required for the coal fines to return to the surface in the Wuxiang block was calculated to be 8.55 m3/d. This work can provide a scientific basis for the prevention and control of coal fines in deep CBM wells.

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice.

Premature ovarian insufficiency (POI) is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40. It represents a significant detriment to female fertility. However, the known POI-causative genes currently account for only a fraction of cases. To elucidate the genetic factors underlying POI, we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111. In a subsequent replication study involving 1,030 POI patients, this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants. These variants collectively account for eight cases, representing 0.78% of the study cohort. A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants. Notably, RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-ß/BMP signaling pathway. Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice, monkeys, and humans. To further investigate the functional implications of RNF111 variants, we generated two mouse models: one with a heterozygous missense mutation (Rnf111+/M) and another with a heterozygous null mutation (Rnf111+/-). Both mouse models exhibited impaired female fertility, characterized by reduced litter sizes and small ovarian reserve. Additionally, RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries. In conclusion, our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

Diffusion-based deep learning method for augmenting ultrastructural imaging and volume electron microscopy.

Electron microscopy (EM) revolutionized the way to visualize cellular ultrastructure. Volume EM (vEM) has further broadened its three-dimensional nanoscale imaging capacity. However, intrinsic trade-offs between imaging speed and quality of EM restrict the attainable imaging area and volume. Isotropic imaging with vEM for large biological volumes remains unachievable. Here, we developed EMDiffuse, a suite of algorithms designed to enhance EM and vEM capabilities, leveraging the cutting-edge image generation diffusion model. EMDiffuse generates realistic predictions with high resolution ultrastructural details and exhibits robust transferability by taking only one pair of images of 3 megapixels to fine-tune in denoising and super-resolution tasks. EMDiffuse also demonstrated proficiency in the isotropic vEM reconstruction task, generating isotropic volume even in the absence of isotropic training data. We demonstrated the robustness of EMDiffuse by generating isotropic volumes from seven public datasets obtained from different vEM techniques and instruments. The generated isotropic volume enables accurate three-dimensional nanoscale ultrastructure analysis. EMDiffuse also features self-assessment functionalities on predictions' reliability. We envision EMDiffuse to pave the way for investigations of the intricate subcellular nanoscale ultrastructure within large volumes of biological systems.

Germline Mutational Landscape and Novel Targetable RAD51D Variant in Chinese Patients With Ovarian Cancer.

PURPOSE: Genetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant. METHODS: Between 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2, other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays. RESULTS: Overall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin. CONCLUSION: Our study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.

[The Research Progress in the Diagnosis and Treatment of Primary Intestinal Diffuse Large B-cell Lymphoma--Review].

Primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is clinically rare, but in recent years, with the gradual maturity of pathology and molecular biology technology, its incidence rate and diagnosis rate have also increased. Due to the lack of specificity of the clinical symptoms of PI-DLBCL, it is easy to misdiagnose and miss the diagnosis, and there is no consensus on the best treatment of PI-DLBCL in clinical practice. Therefore, by retrieving the latest literature at home and abroad, this review systematically discusses the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of PI-DLBCL, in order to improve the understanding of rare PI-DLBCL in hematology and oncology, and provide reference for basic research and clinical diagnosis and treatment of PI-DLBCL.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Objective: Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. Methods: This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Conclusion: Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Comprehensive assessment of ocular parameters for identifying diagnostic indicators of diabetic peripheral neuropathy.

PURPOSE: To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis. METHODS: Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM). RESULT: Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8. CONCLUSION: The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management.

Low serum apolipoprotein A1 impairs antitumor immunity of CD8+ T cells via the HIF-1α-glycolysis pathway.

An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer tissues, the low serum ApoA1 group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing ApoA1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T cell-dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α-mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing ApoA1 transgenic mice showed an increased response to anti-PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α-mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti-PD-1 therapy for treating cancer.

hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring anti-apoptotic miRNAs.

Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods including mesenchymal stem cell (MSC) transplant and hormone replacement therapy have limited clinical application due to their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line. The results showed that hUCMSC-EVs significantly attenuated body weight loss, ovarian weight loss, ovary atrophy, and follicle loss in moderate-dose (1.5 mg/kg) CDDP-induced POI mice, similar to the effects observed with hUCMSCs. We further discovered that the hUCMSC-EVs might inhibit CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic miRNA levels in GCs, thereby downregulating the mRNA levels of multiple pro-apoptotic genes. In general, our findings indicate that moderate-dose chemotherapy may be a better choice for clinical oncotherapy considering the effective rescue of oncotherapy-induced ovarian damage with hUCMSC-EVs. Additionally, multiple miRNAs in hUCMSC-EVs may potentially be used to inhibit chemotherapy-induced ovarian GC apoptosis, thereby restoring ovarian function and improving the life quality of female cancer patients.

Heart and great vessels segmentation in congenital heart disease via CNN and conditioned energy function postprocessing.

PURPOSE: The segmentation of the heart and great vessels in CT images of congenital heart disease (CHD) is critical for the clinical assessment of cardiac anomalies and the diagnosis of CHD. However, the diverse types and abnormalities inherent in CHD present significant challenges to comprehensive heart segmentation. METHODS: We proposed a novel two-stage segmentation approach, integrating a Convolutional Neural Network (CNN) with a postprocessing method with conditioned energy function for pulmonary and aorta. The initial stage employs a CNN enhanced by a gated self-attention mechanism for the segmentation of five primary heart structures and two major vessels. Subsequently, the second stage utilizes a conditioned energy function specifically tailored to refine the segmentation of the pulmonary artery and aorta, ensuring vascular continuity. RESULTS: Our method was evaluated on a public dataset including 110 3D CT volumes, encompassing 16 CHD variants. Compared to prevailing segmentation techniques (U-Net, V-Net, Unetr, dynUnet), our approach demonstrated improvements of 1.02, 1.04, and 1.41% in Dice Coefficient (DSC), Intersection over Union (IOU), and the 95th percentile Hausdorff Distance (HD95), respectively, for heart structure segmentation. For the two great vessels, the enhancements were 1.05, 1.07, and 1.42% in these metrics. CONCLUSION: The outcomes on the public dataset affirm the efficacy of our proposed segmentation method. Precise segmentation of the entire heart and great vessels can significantly aid in the diagnosis and treatment of CHD, underscoring the clinical relevance of our findings.

PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. METHODS: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. RESULTS: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). CONCLUSIONS: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

Development and psychometric evaluation of beliefs about the orthokeratology lens compliance scale (BOLCS): Based on the theory of planned behavior.

PURPOSE: Non-adherence to standard wear, care, and follow-up procedures is a major risk factor for contact lens-related complications. The effectiveness of orthokeratology largely depends on the wearer's adherence. However, a deficiency in scales capturing adherence beliefs pertinent to orthokeratology exacerbates the lack of guidance for effective intervention strategies. The purpose of this study is to develop and evaluate the psychometric properties of a new scale based on the Theory of Planned Behavior that assesses the level of adherence among ortho-k wearers. METHODS: This study involved three stages following the STROBE checklist: (1) developing initial scale items based on the Theory of Planned Behavior, a literature review, and a qualitative study; (2) evaluation of content and face validity; (3) psychometric testing on 296 participants. Item analysis, based on Classical Test Theory, assessed the overall consistency, reliability, and validity of the scale. RESULTS: The final 37-item Beliefs about the Orthokeratology Lens Compliance Scale (BOLCS) comprises 11 dimensions. The Cronbach's alpha coefficients for each dimension ranged from 0.560 to 0.798. The folded half reliabilities were 0.845, and the combined reliabilities ranged from 0.676 to 0.793, indicating strong reliability. Item-level CVI (I-CVI) and scale-level CVI/average (S-CVI/Ave) values, assessed by the panel, ranged from 0.71 to 1 and 0.954, respectively. Exploratory and confirmatory factor analyses supported a factor structure consistent with the theoretical model. CONCLUSIONS: The scale's construction adhered to a standardized process, yielding preliminary validation results with satisfactory reliability and validity.