Partial order relation-based gene ontology embedding improves protein function prediction.

Protein annotation has long been a challenging task in computational biology. Gene Ontology (GO) has become one of the most popular frameworks to describe protein functions and their relationships. Prediction of a protein annotation with proper GO terms demands high-quality GO term representation learning, which aims to learn a low-dimensional dense vector representation with accompanying semantic meaning for each functional label, also known as embedding. However, existing GO term embedding methods, which mainly take into account ancestral co-occurrence information, have yet to capture the full topological information in the GO-directed acyclic graph (DAG). In this study, we propose a novel GO term representation learning method, PO2Vec, to utilize the partial order relationships to improve the GO term representations. Extensive evaluations show that PO2Vec achieves better outcomes than existing embedding methods in a variety of downstream biological tasks. Based on PO2Vec, we further developed a new protein function prediction method PO2GO, which demonstrates superior performance measured in multiple metrics and annotation specificity as well as few-shot prediction capability in the benchmarks. These results suggest that the high-quality representation of GO structure is critical for diverse biological tasks including computational protein annotation.

Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

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.

CD1d protects against hepatocyte apoptosis in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.

On-Demand 3D Spatial Distribution of Magnetic Permeability Based on Fe3 O4 Nanoparticle Liquid Toward Micro-Cavity Detectors.

The change of 3D spatial distribution of magnetic permeability can lead to the generation of introduced electrical signals. However, present studies can only achieve rough regulation by simple shape deformation of magnetic elastomers such as compression, bending, or stretching. Accurate control of the 3D spatial distribution of magnetic permeability is still an open question. In this study, an on-demand 3D spatial distribution of magnetic permeability by controlled flowing of Fe3 O4 nanoparticle liquid (FNL) is demonstrated. The flowing routes of FNL are tuned by a 3D-printed cage with pre-designed hollow structure, thus changing the 3D spatial distribution of magnetic permeability. Then, eight symmetrically distributed coils under cage are used to receive characteristic induction voltage signals. Maxwell numerical simulation reveals the working mechanism of signal generation. Notably, those eight coils can detect FNL flowing status in eight directions, allowing recognition of up to 255 different FNL flowing combinations. By introducing machine learning, the micro-cavity detector based on FNL can distinguish nine kinds of micro-cavity structures with an accuracy of 98.77%. This work provides a new strategy for the adjustment of the 3D spatial distribution of the magnetic permeability and expands the application of FNL in the field of space exploration.

TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.

Ovarian cancer is a major cause of death among cancer patients. Recent research has shown that the transmembrane emp24 domain (TMED) protein family plays a role in the progression of various types of cancer. In this study, we investigated the expression of TMED3 in ovarian cancer tumors compared to nontumor tissues using immunohistochemical staining. We found that TMED3 was overexpressed in ovarian cancer tumors, and its high expression was associated with poor disease-free and overall survival. To understand the functional implications of TMED3 overexpression in ovarian cancer, we conducted experiments to knockdown TMED3 using short hairpin RNA (shRNA). We observed that TMED3 knockdown resulted in reduced cell viability and migration, as well as increased cell apoptosis. Additionally, in subcutaneous xenograft models in BALB-c nude mice, TMED3 knockdown inhibited tumor growth. Further investigation revealed that SMAD family member 2 (SMAD2) was a downstream target of TMED3, driving ovarian cancer progression. TMED3 stabilized SMAD2 by inhibiting the E3 ligase NEDD4-mediated ubiquitination of SMAD2. To confirm the importance of SMAD2 in TMED3-mediated ovarian cancer, we performed functional rescue experiments and found that SMAD2 played a critical role in this process. Moreover, we discovered that the PI3K-AKT pathway was involved in the promoting effects of TMED3 overexpression on ovarian cancer cells. Overall, our study identifies TMED3 as a prognostic indicator and tumor promoter in ovarian cancer. Its function is likely mediated through the regulation of the SMAD2 and PI3K-AKT signaling pathway. These findings contribute to our understanding of the molecular mechanisms underlying ovarian cancer progression and provide potential targets for therapeutic intervention.

R-loops act as regulatory switches modulating transcription of COLD-responsive genes in rice.

COLD is a major naturally occurring stress that usually causes complex symptoms and severe yield loss in crops. R-loops function in various cellular processes, including development and stress responses, in plants. However, how R-loops function in COLD responses is largely unknown in COLD susceptible crops like rice (Oryza sativa L.). We conducted DRIP-Seq along with other omics data (RNA-Seq, DNase-Seq and ChIP-Seq) in rice with or without COLD treatment. COLD treatment caused R-loop reprogramming across the genome. COLD-biased R-loops had higher GC content and novel motifs for the binding of distinct transcription factors (TFs). Moreover, R-loops can directly/indirectly modulate the transcription of a subset of COLD-responsive genes, which can be mediated by R-loop overlapping TF-centered or cis-regulatory element-related regulatory networks and lncRNAs, accounting for c. 60% of COLD-induced expression of differential genes in rice, which is different from the findings in Arabidopsis. We validated two R-loop loci with contrasting (negative/positive) roles in the regulation of two individual COLD-responsive gene expression, as potential targets for enhanced COLD resistance. Our study provides detailed evidence showing functions of R-loop reprogramming during COLD responses and provides some potential R-loop loci for genetic and epigenetic manipulation toward breeding of rice varieties with enhanced COLD tolerance.

Prognostic factors and the role of primary debulking in operable stage IVB ovarian cancer with supraclavicular lymph node metastasis: a retrospective study in Chinese patients.

BACKGROUND: Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. METHODS: We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). RESULTS: In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as "continuous-metastasis type", while the other 7 (13.7%) defined as "skip-metastasis type". Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3-63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that "continuous-metastasis type" had longer OS and PFS than "skip-metastasis type" (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among "continuous-metastasis type" patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. CONCLUSIONS: In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

BACKGROUND: Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. PURPOSE: To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. STUDY TYPE: Retrospective. POPULATION: Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. ASSESSMENT: EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. STATISTICAL TESTS: Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. RESULTS: EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). DATA CONCLUSION: The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Unique three-dimensional ordered macroporous dealloyed gold-silver electrochemical sensing platforms for ultrasensitive mercury(II) monitoring.

To address the requirement of ultra-sensitive detection of trace mercury(II) (Hg2+) ions in the environment and food, we developed an electrochemical biosensor with super-sensitivity, extremely high selectivity, and reusability. This biosensor comprised two signal amplification components: a three-dimensional macroporous dealloyed (3DOMD) Au-Ag thin-film electrode and a multifunctional encoded Au@Pt nanocage (APNC). As a platform for immobilized capture DNA (cDNA), a 3DOMD Au-Ag thin film prepared by a dealloying method with an active surface area 4.8 times higher than that of 3D macroporous gold films generated by cyclic voltammetry (CV) with sulfuric acid was capable of increasing the sensing surface area while also strengthening the electron transport capacity of the sensing substrate due to its multilayered multi-porous framework. In the presence of Hg2+, probe DNA (pDNA) could be hybridized with the mismatched capture DNA (cDNA) through stable thymine-Hg2+-thymine (T-Hg2+-T) linkages, connecting thionine-APNC to the electrode surface and utilizing the large specific surface area to accomplish highly sensitive detection of Hg2+. With an extremely low Hg2+ detection limit of 2 pM and a detection range from 0.01 to 1000 nM, this technique opened up a new avenue for the ultrasensitive detection of a wider range of heavy metal ions or biomolecules.

Restoration of the Mucosal IgA Response by Improving CD4+ T Pyroptosis Fails to Attenuate Gut Bacterial Translocation and Organ Damage After LPS Attack.

BACKGROUND: Currently, the mechanisms of impaired gut mucosal immunity in sepsis remain unclear. Gut immunoglobulin A (IgA) is an important defense mechanism against invasive pathogens, and CD4+ T cells regulate the IgA response. AIM: We aimed to verify the hypothesis indicating that CD4+ T pyroptosis induced by lipopolysaccharide (LPS) leads to an impaired gut IgA response and subsequent bacterial translocation and organ damage. METHODS: Cultured CD4+ T cells and mice were manipulated with LPS, and pyroptosis was improved by A438079 or adoptive CD4+ T cell transfer. The changes demonstrated in pyroptosis-related molecules, cytotoxicity and CD4+ T cells were examined to determine CD4+ T pyroptosis. The changes demonstrated in IgA+ B cells, AID (key enzyme for immunoglobulins) and IgA production and function were examined to evaluate the IgA response. Serum biomarkers, bacterial colonies and survival analysis were detected for bacterial translocation and organ damage. RESULTS: LPS attack induced CD4+ T pyroptosis, as evidenced by increased expression of P2X7, Caspase-11 and cleaved GSDMD, which elevated cytotoxicity and decreased CD4+ T cells. Decreased CD4+ T subsets (Foxp3+ T and Tfh cells) influenced the IgA response, as evidenced by lower AID expression, which decreased IgA+ B cells and IgA production and function. A438079 or cell transfer improved the IgA response but failed to reduce the translocation of gut pathogens, damage to the liver and kidney, and mortality of mice. CONCLUSION: LPS attack results in CD4+ T pyroptosis. Improvement of pyroptosis restores the mucosal IgA response but fails to ameliorate bacterial translocation and organ damage.

Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.

Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.

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.

Endometrioid carcinomas with sex cord-like formations and hyalinization: spontaneous pregnancy after conservative treatment.

Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient's postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes.

Pharmacokinetics and bioequivalence of two metoprolol succinate extended release tablets in healthy Chinese subjects under fasting and fed conditions.

AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release (ER) tablets in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 47.5-mg dose of the test or reference metoprolol ER tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 48 hours after dosing. Plasma concentrations of metoprolol were determined by liquid chromatography. The safety of both ER tablets was monitored throughout the study. RESULTS: 60 subjects were enrolled and all completed the study, with 30 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC0-48h, AUC0-inf, and Cmax were within the acceptable bioequivalence range (80 - 125%). There were no significant differences in adverse event (AE) reporting between the subjects receiving test or reference ER tablet. No serious AEs occurred during the study period. CONCLUSION: The test metoprolol ER tablet was bioequivalent to the reference metoprolol ER tablet (Betaloc ZOK) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

High contrast cartilaginous endplate imaging in spine using three dimensional dual-inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence.

PURPOSE: To investigate the feasibility and application of a novel imaging technique, a three-dimensional dual adiabatic inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence, for high contrast assessment of cartilaginous endplate (CEP) imaging with head-to-head comparisons between other UTE imaging techniques. METHOD: The DIR-UTE sequence employs two narrow-band adiabatic full passage (AFP) pulses to suppress signals from long T2 water (e.g., nucleus pulposus (NP)) and bone marrow fat (BMF) independently, followed by multispoke UTE acquisition to detect signals from the CEP with short T2 relaxation times. The DIR-UTE sequence, in addition to three other UTE sequences namely, an IR-prepared and fat-saturated UTE (IR-FS-UTE), a T1-weighted and fat-saturated UTE sequence (T1w-FS-UTE), and a fat-saturated UTE (FS-UTE) was used for MR imaging on a 3 T scanner to image six asymptomatic volunteers, six patients with low back pain, as well as a human cadaveric specimen. The contrast-to-noise ratio of the CEP relative to the adjacent structures-specifically the NP and BMF-was then compared from the acquired images across the different UTE sequences. RESULTS: For asymptomatic volunteers, the DIR-UTE sequence showed significantly higher contrast-to-noise ratio values between the CEP and BMF (CNRCEP-BMF) (19.9 ± 3.0) and between the CEP and NP (CNRCEP-NP) (23.1 ± 1.7) compared to IR-FS-UTE (CNRCEP-BMF: 17.3 ± 1.2 and CNRCEP-NP: 19.1 ± 1.8), T1w-FS-UTE (CNRCEP-BMF: 9.0 ± 2.7 and CNRCEP-NP: 10.4 ± 3.5), and FS-UTE (CNRCEP-BMF: 7.7 ± 2.2 and CNRCEP-NP: 5.8 ± 2.4) for asymptomatic volunteers (all P-values < 0.001). For the spine sample and patients with low back pain, the DIR-UTE technique detected abnormalities such as irregularities and focal defects in the CEP regions. CONCLUSION: The 3D DIR-UTE sequence is able to provide high-contrast volumetric CEP imaging for human spines on a clinical 3 T scanner.

High-frequency Quantitative Ultrasound Imaging of Human Rotator Cuff Muscles: Assessment of Repeatability and Reproducibility.

This study evaluated the repeatability and reproducibility of using high-frequency quantitative ultrasound (QUS) measurement of backscatter coefficient (BSC), grayscale analysis, and gray-level co-occurrence matrix (GLCM) textural analysis, to characterize human rotator cuff muscles. The effects of varying scanner settings across two different operators and two US systems were investigated in a healthy volunteer with normal rotator cuff muscles and a patient with chronic massive rotator cuff injury and substantial muscle degeneration. The results suggest that BSC is a promising method for assessing rotator cuff muscles in both control and pathological subjects, even when operators were free to adjust system settings (depth, level of focus, and time-gain compensation). Measurements were repeatable and reproducible across the different operators and ultrasound imaging platforms. In contrast, grayscale and GLCM analyses were found to be less reliable in this setting, with significant measurement variability. Overall, the repeatability and reproducibility measurements of BSC indicate its potential as a diagnostic tool for rotator cuff muscle evaluation.

Deep learning in the diagnosis of maxillary sinus diseases: A systematic review.

OBJECTIVES: To assess the performance of deep learning (DL) in the detection, classification, and segmentation of maxillary sinus diseases. MATERIALS AND METHODS: An electronic search was conducted by two reviewers on databases including PubMed, Scopus, Cochrane, and IEEE. All English papers published no later than February 7, 2024, were evaluated. Studies related to DL for diagnosing maxillary sinus diseases were also searched in journals manually. RESULTS: 14 of 1167 studies were eligible according to the inclusion criteria. All studies trained DL models based on radiographic images. Six studies applied to detection tasks, one focused on classification, two segmented lesions, and five studies made a combination of 2 types of DL models. The accuracy of the DL algorithms ranged from 75.7% to 99.7%, and the area under curves (AUC) varied between 0.7 and 0.997. CONCLUSION: DL can accurately deal with the tasks of diagnosing maxillary sinus diseases. Students, residents, and dentists could be assisted by DL algorithms to diagnose and make rational decisions on implant treatment related to maxillary sinuses.

The comparison of fluidized positioners and traditional gel pads for skin protection in neurosurgical patients undergoing lateral and prone positions: A retrospective analysis with propensity score matching method.

To compare fluidized positioners and gel pads for skin protection in neurosurgery patients placed in lateral and prone positions. It is one of the major challenges that operating room nurses face in protecting the skin during the long duration of neurosurgery. Currently, there are increasing tools available to protect the skin under pressure, and various tools practice well in the clinic. Fluidized positioners are newly emerging protective pads that have been clinically effective in protecting the skin, but no studies have compared them to previous pads. This is a retrospective cohort study. Data from 706 patients who underwent neurosurgery between January 2018 and December 2021 were systemically reviewed. Patients undergoing long-term neurosurgery in the neurosurgical lateral and prone positions were divided into two groups: fluidized positioners or gel pads. Propensity score matching (PSM) was performed for group balance (1:1 ratio) using the following baseline characteristics: age, gender, ASA (American Society of Anesthesiologists) classification, duration of surgery, surgical position and underlying disease. The incidence of decubitus, and length of stay (LOS) in the hospital were compared between the two groups. The results were obtained for 394 patients in the fluidized positioner group with a 3.8% incidence of pressure ulcers and 312 patients in the gel pad group with an 8% incidence of pressure ulcers, which were unbalanced in terms of gender, ASA, hypertension and diabetes data. After a PSM, patients were compared in terms of pressure ulcer incidence (3.7% vs. 7.8%, p = 0.034) and LOS (22.35 vs. 25.65 days, p < 0.001). Fluidized positioners can effectively reduce the incidence of pressure injury in lateral and prone positions of neurosurgery. The results of this study may contribute to the development of policies to prevent the development of pressure ulcers during neurosurgical procedures.

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3. / C3沉积为主的肾小球肾炎52ä¾‹ä¸´åºŠä¸Žç— ç†ç‰¹å¾.

OBJECTIVES: With the in-depth study of complement dysregulation, glomerulonephritis with dominant C3 has received increasing attention, with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types. This study analyzes the clinical, pathological, and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3, aiming to avoid misdiagnosis and missed diagnoses. METHODS: The clinical, pathological, and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed. According to the clinical feature and results of pathology, 15 patients with post-infectious glomerulonephritis (PIGN) and 37 patients with of non-infectious glomerulonephritis (N-PIGN) were classified. N-PIGN subgroup analysis was performed, and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group, or 27 in a C3 glomerulopathy (C3G) group and 10 in a non-C3 nephropathy (N-C3G) group. RESULTS: The PIGN group had lower creatinine values (84.60 µmol/L vs179.62 µmol/L, P=0.001), lower complement C3 values (0.36 g/L vs0.74 g/L, P<0.001) at biopsy, and less severe pathological chronic lesions compared with the N-PIGN group. In the N-PIGN subgroup analysis, the C3-dominant-deposition group had higher creatinine values (235.30 µmol/L vs106.70 µmol/L, P=0.004) and higher 24-hour urine protein values (4 025.62 mg vs1 981.11 mg, P=0.037) than the C3-alone-deposition group. The prognosis of kidney in the PIGN group (P=0.049), the C3-alone-deposition group (P=0.017), and the C3G group (P=0.018) was better than that in the N-PIGN group, the C3-dominant-deposition group, and the N-C3G group, respectively. CONCLUSIONS: Glomerulonephritis with dominant C3 covers a variety of pathological types, and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G; in addition, the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis, and relevant diagnosis, treatment, and follow-up should be strengthened.