Gut complement induced by the microbiota combats pathogens and spares commensals.

Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

naRNA-LL37 composite DAMPs define sterile NETs as self-propagating drivers of inflammation.

Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs). NETs counteract microbes but are also linked to inflammation in atherosclerosis, arthritis, or psoriasis by unknown mechanisms. Here, we report that NET-associated RNA (naRNA) stimulates further NET formation in naive PMNs via a unique TLR8-NLRP3 inflammasome-dependent pathway. Keratinocytes respond to naRNA with expression of psoriasis-related genes (e.g., IL17, IL36) via atypical NOD2-RIPK signaling. In vivo, naRNA drives temporary skin inflammation, which is drastically ameliorated by genetic ablation of RNA sensing. Unexpectedly, the naRNA-LL37 'composite damage-associated molecular pattern (DAMP)' is pre-stored in resting neutrophil granules, defining sterile NETs as inflammatory webs that amplify neutrophil activation. However, the activity of the naRNA-LL37 DAMP is transient and hence supposedly self-limiting under physiological conditions. Collectively, upon dysregulated NET release like in psoriasis, naRNA sensing may represent both a potential cause of disease and a new intervention target.

Endothelial Chromatin-Remodeling Enzymes Regulate the Production of Critical ECM Components During Murine Lung Development.

BACKGROUND: The chromatin-remodeling enzymes BRG1 (brahma-related gene 1) and CHD4 (chromodomain helicase DNA-binding protein 4) independently regulate the transcription of genes critical for vascular development, but their coordinated impact on vessels in late-stage embryos has not been explored. METHODS: In this study, we genetically deleted endothelial Brg1 and Chd4 in mixed background mice (Brg1fl/fl;Chd4fl/fl;VE-Cadherin-Cre), and littermates that were negative for Cre recombinase were used as controls. Tissues were analyzed by immunostaining, immunoblot, and flow cytometry. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression, and chromatin immunoprecipitation revealed gene targets of BRG1 and CHD4 in cultured endothelial cells. RESULTS: We found Brg1/Chd4 double mutants grew normally but died soon after birth with small and compact lungs. Despite having normal cellular composition, distal air sacs of the mutant lungs displayed diminished ECM (extracellular matrix) components and TGFß (transforming growth factor-ß) signaling, which typically promotes ECM synthesis. Transcripts for collagen- and elastin-related genes and the TGFß ligand Tgfb1 were decreased in mutant lung endothelial cells, but genetic deletion of endothelial Tgfb1 failed to recapitulate the small lungs and ECM defects seen in Brg1/Chd4 mutants. We instead found several ECM genes to be direct targets of BRG1 and CHD4 in cultured endothelial cells. CONCLUSIONS: Collectively, our data highlight essential roles for endothelial chromatin-remodeling enzymes in promoting ECM deposition in the distal lung tissue during the saccular stage of embryonic lung development.

Regulating Second Coordination Shell of Ce Atom Site and Reshaping of Carrier Enable Single-Atom Nanozyme to Efficiently Express Oxidase-like Activity.

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.

A radiomics and genomics-derived model for predicting metastasis and prognosis in colorectal cancer.

Approximately 50% of colorectal cancer (CRC) patients would develop metastasis with poor prognosis, therefore, it is necessary to effectively predict metastasis in clinical treatment. In this study, we aimed to establish a machine-learning model for predicting metastasis in CRC patients by considering radiomics and transcriptomics simultaneously. Here, 1023 patients with CRC from three centers were collected and divided into five queues (Dazhou Central Hospital n = 517, Nanchong Central Hospital n = 120 and the Cancer Genome Atlas (TCGA) n = 386). A total of 854 radiomics features were extracted from tumor lesions on CT images, and 217 differentially expressed genes were obtained from non-metastasis and metastasis tumor tissues using RNA sequencing. Based on radiotranscriptomic (RT) analysis, a novel RT model was developed and verified through genetic algorithms (GA). Interleukin (IL)-26, a biomarker in RT model, was verified for its biological function in CRC metastasis. Furthermore, 15 radiomics variables were screened through stepwise regression, which was highly correlated with the IL26 expression level. Finally, a radiomics model (RA) was established by combining GA and stepwise regression analysis with radiomics features. The RA model exhibited favorable discriminatory ability and accuracy for metastasis prediction in two independent verification cohorts. We designed multicenter, multi-scale cohorts to construct and verify novel combined radiomics and genomics models for predicting metastasis in CRC. Overall, RT model and RA model might help clinicians in directing personalized diagnosis and therapeutic regimen selection for patients with CRC.

Quantification of Binding of Small Molecules to Native Proteins Overexpressed in Living Cells.

The affinity and selectivity of small molecules for proteins drive drug discovery and development. We report a fluorescent probe cellular binding assay (FPCBA) for determination of these values for native (untagged) proteins overexpressed in living cells. This method uses fluorophores such as Pacific Blue (PB) linked to cell-permeable protein ligands to generate probes that rapidly and reversibly equilibrate with intracellular targets, as established by kinetic assays of cellular uptake and efflux. To analyze binding to untagged proteins, an internal ribosomal entry site (IRES) vector was employed that allows a single mRNA to encode both the protein target and a separate orthogonal fluorescent protein (mVenus). This enabled cellular uptake of the probe to be correlated with protein expression by flow cytometry, allowing measurement of cellular dissociation constants (Kd) of the probe. This approach was validated by studies of the binding of allosteric activators to eight different Protein Kinase C (PKC) isozymes. Full-length PKCs expressed in transiently transfected HEK293T cells were used to measure cellular Kd values of a probe comprising PB linked to the natural product phorbol via a carbamate. These values were further used to determine competitive binding constants (cellular Ki values) of the nonfluorescent phorbol ester PDBu and the anticancer agent bryostatin 1 for each isozyme. For some PKC-small molecule pairs, these cellular Ki values matched known biochemical Ki values, but for others, altered selectivity was observed in cells. This approach can facilitate quantification of interactions of small molecules with physiologically relevant native proteins.

Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway.

Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.

A novel model for predicting prognosis and response to immunotherapy in nasopharyngeal carcinoma patients.

Blood-based biomarkers of immune checkpoint inhibitors (ICIs) response in patients with nasopharyngeal carcinoma (NPC) are lacking, so it is necessary to identify biomarkers to select NPC patients who will benefit most or least from ICIs. The absolute values of lymphocyte subpopulations, biochemical indexes, and blood routine tests were determined before ICIs-based treatments in the training cohort (n = 130). Then, the least absolute shrinkage and selection operator (Lasso) Cox regression analysis was developed to construct a prediction model. The performances of the prediction model were compared to TNM stage, treatment, and Epstein-Barr virus (EBV) DNA using the concordance index (C-index). Progression-free survival (PFS) was estimated by Kaplan-Meier (K-M) survival curve. Other 63 patients were used for validation cohort. The novel model composed of histologic subtypes, CD19+ B cells, natural killer (NK) cells, regulatory T cells, red blood cells (RBC), AST/ALT ratio (SLR), apolipoprotein B (Apo B), and lactic dehydrogenase (LDH). The C-index of this model was 0.784 in the training cohort and 0.735 in the validation cohort. K-M survival curve showed patients with high-risk scores had shorter PFS compared to the low-risk groups. For predicting immune therapy responses, the receiver operating characteristic (ROC), decision curve analysis (DCA), net reclassifcation improvement index (NRI) and integrated discrimination improvement index (IDI) of this model showed better predictive ability compared to EBV DNA. In this study, we constructed a novel model for prognostic prediction and immunotherapeutic response prediction in NPC patients, which may provide clinical assistance in selecting those patients who are likely to gain long-lasting clinical benefits to anti-PD-1 therapy.

Camrelizumab plus gemcitabine and oxaliplatin for relapsed or refractory classical Hodgkin lymphoma: a phase II trial.

BACKGROUND: Classical Hodgkin lymphoma (cHL) is a highly curable disease, while novel therapy is needed for refractory or relapsed (R/R) patients. This phase II trial aimed to evaluate the role of camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in R/R cHL patients. METHODS: Transplant-eligible patients with R/R cHL were enrolled and received two 14-day cycles of camrelizumab 200 mg intravenously (IV) and two 28-day cycles of camrelizumab 200 mg IV, gemcitabine 1000 mg/m2 IV, and oxaliplatin 100 mg/m2 IV on days 1 and 15. Patients with partial response (PR) or stable disease received an additional cycle of combination therapy. Those who achieved complete response (CR) or PR proceeded to autologous stem cell transplantation (ASCT). The primary endpoint was the CR rate at the end of protocol therapy before ASCT. RESULTS: Forty-two patients were enrolled. At the end of protocol therapy, the objective response rate and CR rate were 94.9% (37/39) and 69.2% (27/39) in the evaluable set, and 88.1% (37/42) and 64.3% (27/42) in the full analysis set, respectively. Twenty-nine patients (69.0%) proceeded to ASCT, and 4 of 5 patients with PR achieved CR after ASCT. After a median follow-up of 20.7 months, the 12-month progression-free survival rate was 96.6% and the 12-month overall survival rate was 100%. Grade 3 or higher treatment emergent adverse events occurred in 28.6% of patients (12/42), mainly hematological toxicity. CONCLUSIONS: Camrelizumab combined with GEMOX constitutes an effective salvage therapy for R/R cHL, proving to be relatively well-tolerated and facilitating ASCT in most patients, thus promoting sustained remission. TRIAL REGISTRATION: ClinicalTrials.gov NCT04239170. Registered on January 1, 2020.

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field.

The prevalence of obstructive sleep apnea syndrome after COVID-19 infection.

Obstructive sleep apnea is a well-known risk factor regarding the severity of COVID-19 infection. However, to date, relatively little research performed on the prevalence of obstructive sleep apnea in COVID-19 survivors. The purpose of this study was to investigate the risk of obstructive sleep apnea after COVID-19 infection. This study was based on data collected from the US Collaborative Network in TriNetX. From January 1, 2020 to June 30, 2022, participants who underwent the SARS-CoV-2 test were included in the study. Based on their positive or negative results of the COVID-19 test results (the polymerase chain reaction [PCR] test), we divided the study population into two groups. The duration of follow-up began when the PCR test was administered and continued for 12 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) for newly recorded COVID-19 positive subjects for obstructive sleep apnea were calculated using the Cox proportional hazards model and compared to those without COVID-19 infection. Subgroup analyses were performed for the age, sex, and race, groups. The COVID-19 group was associated with an increased risk of obstructive sleep apnea, at both 3 months of follow-up (HR: 1.51, 95% CI: 1.48-1.54), and 1 year of follow-up (HR: 1.57, 95% CI: 1.55-1.60). Kaplan-Meier curves regarding the risk of obstructive sleep apnea revealed a significant difference of probability between the two cohorts in the follow-up periods of 3 months and 1 year (Log-Rank test, p < 0.001). The risks of obstructive sleep apnea among COVID-19 patients were significant in the less than 65 year of age group (HR: 1.50, 95% CI: 1.47-1.52), as well as in the group older than or equal to 65 years (HR:1.69, 95% CI: 1.64-1.73). Furthermore, the risks of obstructive sleep apnea were evident in both the male and female COVID-19 groups. Compared to the control group, the risks of obstructive sleep apnea in the COVID-19 participants increased in the subgroups of White (HR: 1.62, 95% CI: 1.59-1.64), Blacks/African Americans (HR: 1.50, 95% CI: 1.45-1.55), Asian (HR: 1.46, 95% CI: 1.32-1.62) and American Indian/Alaska Native (HR: 1.36, 95% CI: 1.07-1.74). In conclusion, the incidence of new diagnosis obstructive sleep apnea could be substantially higher after COVID-19 infection than non-COVID-19 comparison group. Physicians should evaluate obstructive sleep apnea in patients after COVID-19 infection to help prevent future long-term adverse effects from occurring in the future, including cardiovascular and neurovascular disease.

Population structure in Mixornis tit-babblers across Sunda Shelf matches interfluvia of paleo-rivers.

Rivers constitute an important biogeographic divide in vast areas of tropical rainforest, such as the Amazon and Congo Basins. Southeast Asia's rainforests are currently fragmented across islands divided by sea, which has long obscured their extensive history of terrestrial connectivity as part of a vast (but now submerged) subcontinent - Sundaland - during most of the Quaternary. The role of paleo-rivers in determining population structure in Sundaic rainforests at a time when these forests were connected remains little understood. We examined the coloration of museum skins and used the genomic DNA of museum samples and freshly-collected blood tissue of a pair of Sundaic songbird species, the pin-striped and bold-striped tit-babblers (Mixornis gularis and M. bornensis, respectively), to assess the genetic affinity of populations on small Sundaic islands that have largely been ignored by modern research. Our genomic and morphological results place the populations from the Anambas and Natuna Islands firmly within M. gularis from the Malay Peninsula in western Sundaland, even though some of these islands are geographically much closer to Borneo, where M. bornensis resides. Our results reveal genetic structure consistent with the course of Sundaic paleo-rivers and the location of the interfluvia they formed, and add to a small but growing body of evidence that rivers would have been of equal biogeographic importance in Sundaland's former connected forest landscape as they are in Amazonia and the Congo Basin today.

Surface-engineered erythrocyte membrane-camouflage fluorescent bioprobe for precision ovarian cancer surgery.

PURPOSE: Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P). METHODS: AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh3 (P), with functional erythrocyte membrane modified by a modular peptide (AR). Interestingly, AR was composed of an asymmetric tripodal pentapeptide scaffold (GGKGG) with three appended modulars: KPSSPPEE (A6) peptide, RRRR (R4) peptide and cholesterol. To verify the specificity of the probe in vitro, SKOV3 cells with overexpression of CD44 were used as the positive group, and HLF cells with low expression of CD44 were devoted as the control group. The AR-M@HMSN@P fluorescence imaging was utilized to provide surgical guidance for the removal of micro-metastatic lesions. RESULTS: In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance. CONCLUSION: We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.

The residual cancer burden index as a valid prognostic indicator in breast cancer after neoadjuvant chemotherapy.

PURPOSE: The residual cancer burden index (RCB) was proposed as a response evaluation criterion in breast cancer patients treated with Neoadjuvant Chemotherapy (NAC). This study evaluated the relevance of RCB with replase-free survival (RFS). METHODS: The clinical data of 254 breast cancer patients who received NAC between 2016 and 2020 were retrospectively collected. The relationship between clinicopathologic factors and RFS was evaluated using Cox proportional hazards regression models. RFS estimates were determined by Kaplan-Meier(K-M) analysis and compared using the log-rank test. Multivariate logistic regression analysis was used to evaluate the risk factors associated with RCB. Receiver operating characteristic (ROC) curves showed the potential of the RCB and MP grading systems as biomarkers for RFS. RESULTS: At a median follow-up of 52 months, 59 patients(23.23%) developed relapse. Multivariate Cox regression showed that older age (P = 0.022), high Pathologic T stage after NAC (P = 0.023) and a high RCB score(P = 0.003) were risk factors for relapse. The outcomes of the multivariate logistic analysis indicated that RCB 0 (pathologic complete response [pCR]) was associated with HER2-positive patients (P = 0.002) and triple-negative breast cancer (TNBC) patients (P = 0.013). In addition, the RCB and MP scoring systems served as prognostic markers for patients who received NAC, and their area under curves (AUCs) were 0.691 and 0.342, respectively. CONCLUSION: These data suggest that RCB can be equally applied to predict RFS in Chinese patients with NAC. The application of RCB may help guide the selection of treatment strategies.

Immunotyping of peripheral blood lymphocytes by flow cytometry reveals Th cell as a potential prognostic biomarker for extranodal NK/T-cell lymphoma.

This study aimed to explore the distribution, characteristics and prognostic value of baseline peripheral blood lymphocyte subsets in patients with extranodal NK/T-cell lymphoma (NKTCL). We conducted this cross-sectional study of 205 newly-diagnosed NKTCL patients receiving first-line chemotherapy and radiation at our institute between 2010 and 2020. Baseline peripheral blood lymphocytes were detected using flow cytometry, and the clinical value was analyzed. Compared with healthy controls, patients with NKTCL presented with a distinct peripheral immunity with higher levels of cytotoxic CD8+ T cells (33.230 ± 12.090% vs. 27.060 ± 4.010%, p < 0.001) and NKT cells (7.697 ± 7.219% vs. 3.550 ± 2.088%, p < 0.001) but lower proportions of suppressive regulatory T cells (Treg, 2.999 ± 1.949% vs. 3.420 ± 1.051%, p = 0.003) and CD4+ helper T cells (Th, 33.084 ± 11.361% vs. 37.650 ± 3.153%, p < 0.001). Peripheral lymphocytes were differentially distributed according to age, stage, and primary site in patients with NKTCL. The proportion of Th cells/lymphocytes was associated with tumor burden reflected by stage (p = 0.037), serum lactate dehydrogenase (p = 0.0420), primary tumor invasion (p = 0.025), and prognostic index for NK/T-cell lymphoma (PINK) score (p = 0.041). Furthermore, elevated proportions of T cells (58.9% vs. 76.4%, p = 0.005), Th cells (56.3% vs. 68.8%, p = 0.047), or Treg cells (49.5% vs. 68.9%, p = 0.040) were associated with inferior 5-year progression-free survivals (PFS) via univariable survival analysis. Multivariate cox regression revealed elevated Th cells as an independent predictor for unfavorable PFS (HR = 2.333, 95% CI, 1.030-5.288, p = 0.042) in NKTCL. These results suggested the proportion of Th cells positively correlated with tumor burden and was a potential non-invasive biomarker for inferior survival for patients with NKTCL.

IVF and obstetric outcomes among women of advanced maternal age (≥45 years) using donor eggs.

RESEARCH QUESTION: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? DESIGN: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. RESULTS: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. CONCLUSIONS: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

The effect of reward expectation on working memory of emotional faces under different levels of cognitive load: an ERP study.

Using event-related potentials (ERPs), this study examined the impact of reward expectations on working memory of emotional faces under different levels of cognitive load in a task combining the N-back paradigm and the reward expectation paradigm. The experiment involved presenting high- or low-reward cues followed by an N-back task for emotional faces with different loads. The accuracy results showed that under a high task load, both reward and emotion effects were significantly observed. However, these effects disappeared under a low task load. Analysis of the ERP data revealed that the early P2 and VPP components exhibited greater responses to fearful faces than to neutral faces. In the later stages, the P3 and LPP components showed greater reactions to high rewards than to low rewards. Additionally, the P2 component was found to be modulated by task load in relation to rewards, the EPN component demonstrated task load modulation with respect to emotions, and the N170 component showed an interaction effect between rewards and emotions. These findings imply that load regulates the reward effect and the emotional superiority effect in the process of working memory for emotional faces. In the cognitive processing of working memory, motivation and emotion jointly influence processing. Emotional factors have a greater impact in the early stage of processing, while motivation factors have a greater impact in the late stage of processing.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.