Analysis of the Clinical Predictive Value of the Novel Inflammatory Indices SII, SIRI, MHR and NHR in Patients with Acute Myocardial Infarction and Their Extent of Coronary Artery Disease.

Background: This study aims to observe the relationship between novel inflammatory markers and AMI, and analyze its correlation with the degree of coronary artery disease. Methods: Clinical data were collected from the control (510 cases) and AMI (406 cases) groups. The AMI group was classified into mild, moderate and severe according to the Gensini score. Correlation of SII, SIRI, MHR and NHR with Gensini score in AMI patients was analysed using Spearman rank correlation analysis. Factors influencing the degree of coronary lesion in AMI were analysed by multi-factor ordinal logistic regression. The predictive value of the novel inflammatory markers for AMI and its coronary severity was assessed using ROC curves. Risk prediction of the extent of coronary artery disease in AMI using the Nomogram for novel inflammatory indices. Results: The levels of SII, SIRI, MHR and NHR were significantly higher in the AMI group than in the control group. With increasing Gensini score, all four novel inflammatory indices showed an increasing trend. And four novel inflammatory indices were positively correlated with Gensini scores. Meanwhile, SII, SIRI and MHR were independent risk factors for the extent of coronary artery disease in AMI. SII, SIRI, MHR and NHR have good predictive value for AMI, and have predictive value for mild and severe AMI, but have no predictive value for moderate AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI. Conclusion: The elevated levels of SIRI, SII, MHR, NHR in AMI patients are independent risk factors for the severity of coronary artery disease in AMI patients, and have predictive value to a certain extent.

Novel Colorimetric and Near-Infrared Ratiometric Fluorescent Probe for Sensing Cysteine in Food Samples, Plants, and Living Cells.

Cysteine (Cys) is a crucial biothiol that acts a significant function in food samples and biological systems, including plant roots and living cells. Hence, we developed a novel colorimetric and near-infrared ratiometric fluorescent probe (CT), composed of coumarin and tetrahydroacridine-conjugated indole salt, for the detection of Cys. Upon reaction with Cys, the probe undergoes a specific N-substitution reaction, resulting in a notable colorimetric change and a significant ratiometric fluorescent response in both visible and near-infrared emission channels. These dual-channel ratiometric fluorescence changes are completely independent, enabling the probe to obtain great selectivity, sensitivity, and exceptional detection accuracy. Leveraging these attributes, the probe was employed to provide accurate quantitative analysis of Cys in food samples. Furthermore, confocal imaging demonstrated that the probe could monitor both exogenous and endogenous Cys levels in living cells and track Cys changes in plant roots under heavy metal stress. This work presents a dependable and accurate imaging solution for tracking and identifying Cys of real food, plants, and living cells.

Near-Infrared Ratiometric Hemicyanine Fluorescent Probes for Monitoring Mitochondrial pH Dynamics in Live Cells during Oxidative Stress and Hypoxia.

Novel near-infrared ratiometric molecules (probes A and B) produced by linking formyl-functionalized xanthene and methoxybenzene moieties, respectively, onto a xanthene-hemicyanine framework are detailed. Probe A exhibited a primary absorption peak at 780 nm and a shoulder peak at 730 nm and exhibited fluorescence at 740 nm↓ (signifies a downward shift in intensity upon acidification) in a pH 9.3 buffer and 780 nm↑ at pH 2.8 under excitation at 700 nm. Probe B featured absorptions at 618 and 668 nm at pH 3.2 and at 717 nm at pH 8.6, and fluorescence at 693 nm↑ at pH 3.2 and at 739 nm↓ at pH 8.6, in mostly the red to near-IR region. The ratiometric changes in the intensity of the fluorescent absorptions were reversed between A and B upon acidification as indicated by the arrows. Theoretical calculations confirmed that there were slight changes in conformation between probes and the protonated molecules, suggesting that the changes in emission spectra were due mostly to conjugation effects. Calculations at the APFD/6-311+g(d,p) level with a solvent described by the polarizable continuum model resulted in pK a values for A at 6.33 and B at 6.41, in good agreement with the experimentally determined value of 6.97 and an average of 6.40, respectively. The versatilities of the probes were demonstrated in various experimental contexts, including the effective detection of mitochondrial pH fluctuations. Live cell experiments involving exposure to different pH buffers in the presence of H+ ionophores, monitoring mitophagy processes during cell starvation, studying hypoxia induced by CoCl2 treatment, and investigating responses to various oxidative stresses are detailed. Our findings highlight the potential of attaching xanthene and methoxybenzaldehyde groups onto xanthene-hemicyanine structures as versatile tools for monitoring pH changes in a variety of cellular environments and processes.

Predictive models for breast cancer-related lymphedema after mastectomy.

OBJECTIVES: To establish a nomogram incorporating clinical characteristics to predict the risk of breast cancer-related lymphedema (BCRL). METHODS: In this retrospective study, we included 200 consecutive patients with breast cancer undergoing radical mastectomy from January 2022 to December 2023. Of these, 98 patients diagnosed with BCRL were designated as the experimental group, while 102 patients served as the control group. Logistic regression analyses were conducted to explore factors associated with clinical prognosis and to construct and validate a nomogram for predicting the risk of BCRL using R language version 4.1.2. RESULTS: Univariate and multivariate logistic regression analyses identified six independent risk factors: the number of lymph node dissections (95% CI: 1.425-8.956, P < 0.01), radiotherapy (95% CI: 1.134-2.341, P < 0.01), lack of functional exercise (95% CI: 4.908-19.064, P = 0.001), adjuvant and neoadjuvant chemotherapy (95% CI: 1.763-4.287, P = 0.001), BMI (95% CI: 1.075-2.897, P < 0.05), and hypertension (95% CI: 1.077-2.999, P < 0.05). Using these variables, we developed a nomogram to predict the incidence of BCRL. The AUC value for the model was 0.74 (95% CI: 0.675-0.887), indicating acceptable agreement between predicted and observed outcomes. Decision curve analysis demonstrated good positive net benefits for the model. CONCLUSION: The number of lymph node dissections, radiotherapy, lack of functional exercise, adjuvant and neoadjuvant chemotherapy, BMI, and hypertension are independent risk factors for BCRL. Moreover, the nomogram prediction model showed good predictive performance, high accuracy, and clinical applicability.

Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis.

In this study, we prepared four derivatives of fucosylated chondroitin sulfate (FCS): full-length FCS (flFCS) from Holothuria leucospilota, low molecular weight FCS (lmFCS) derived from flFCS, and their de-branched counterparts, de-branched flFCS (d-flFCS) and de-branched lmFCS (d-lmFCS) via controlled acid treatment. Following structural verification using various analytical techniques, we applied targeted metabolomics to examine the impact of FCS on nutritional efficacy and its structure-activity relationship. Analysis of 225 plasma and feces samples from 75 mice revealed a positive correlation between metabolomic shifts and increased weight gain, underscoring FCS's potential to enhance nutrient absorption and promote growth. The observed linear relationship between the levels of short-chain fatty acids in plasma and feces suggests that FCS may facilitate catabolic activities in the gastrointestinal tract. The comparative study of different FCS derivatives on mouse growth and metabolic homeostasis regulation led to the conclusion that FCS exhibits greater biological activity with a higher degree of branching and larger molecular weight.

Improved reproductive outcomes in normogonadotropic oligomenorrheic women undergoing ovarian stimulation with intrauterine insemination: a retrospective cohort analysis of real-world data.

Purpose: This study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner's sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women. Method: A retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics. Results: Prior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P<0.001). Multivariate regression analyses revealed that menstrual status was a significant independent predictor of both CPR (adjusted odds ratio [OR]=1.83 before PSM, 2.24 after PSM) and LBR (adjusted OR=1.90 before PSM, 2.46 after PSM). In the subgroup analysis, female age was identified as the sole predictor of reproductive outcomes in oligomenorrheic women undergoing OS-IUI. Conversely, in eumenorrheic women, factors such as age, duration of infertility, body mass index (BMI), ovarian stimulation agents, and the number of dominant follicles were significant influencers of CPR and LBR. Conclusion: Normogonadotropic oligomenorrheic women demonstrated improved reproductive outcomes with OS-IUI, suggesting that tailored treatment strategies based on menstrual regularity could optimize success rates in infertility management.

The impact of halo-pelvic traction on sagittal kyphosis in the treatment of severe scoliosis and kyphoscoliosis.

BACKGROUND: Halo-pelvic traction (HPT) is acknowledged for enhancing pulmonary function and reducing neurological complications in severe and rigid scoliosis and kyphoscoliosis. While its role in improving coronal balance is established, its impact on sagittal kyphosis remains under-researched. This study aims to assess HPT's effects on sagittal alignment in these conditions. METHODS: A retrospective review of 37 patients with severe and rigid scoliosis or kyphoscoliosis was conducted to evaluate HPT's efficacy. The analysis focused on the impact of HPT on coronal and sagittal parameters, pulmonary function tests (PFTs) and complications. Radiographic assessments included main cobb angle in coronal, sagittal major kyphosis. RESULTS: HPT was applied for an average of 2.9 months, significantly reducing the primary coronal curve from 127.7°±30.3° to 74.9°±28.3° (P < 0.05), achieving a 41.3% correction rate. Sagittal kyphosis correction was more pronounced, with angles decreasing from 80.4°±26.4° to 41.3°±24.4° (P < 0.05), resulting in a 48.6% correction rate. Pulmonary function tests showed improvements in forced vital capacity (FVC) (from 1.32 ± 0.91 to 1.55 ± 0.83) and forced expiratory volume in 1 s (FEV1) (from 1.03 ± 0.76 to 1.28 ± 0.72), with percentage predicted values also increasing (FVC%: 40.4%±24.3-51.4%±23.1%; FEV1%: 37.8%±25.2-48.1%±22.7%; all P < 0.05). CONCLUSION: HPT effectively reduces spinal deformity severity and improves pulmonary function in patients with severe and rigid scoliosis and kyphoscoliosis. Sagittal kyphosis correction was notably greater than coronal scoliosis correction. The correlation between PFT improvements and coronal curve adjustments suggests that correcting the coronal Cobb angle is pivotal for pulmonary function enhancement.

Novel near-infrared fluorescent probe with large stokes shift for detection of cysteine in food sample and living cells.

Cysteine (Cys) plays a pivotal role in numerous physiological processes and holds significant importance in food analysis. In this study, we designed a novel near-infrared (NIR) fluorescent probe TF for specifically detecting Cys, derived from benzo[e]indole-conjugated tetrahydro-acridine salt. Leveraging the electron-withdrawing properties of the 3,5-bis(trifluoromethyl)benzenethiol group, the probe exhibits a distinctive colorimetric response and a notable enhancement in NIR emission, featuring a substantial Stokes shift of 135 nm, facilitating precise Cys detection. The detection mechanism was elucidated through comprehensive analyses including NMR, MS spectral, and quantum theory calculations. Moreover, the probe demonstrates exceptional attributes such as rapid response (8 min), exceptional selectivity, and sensitivity (with a detection limit as low as 74 nM). The probe's NIR fluorescent response, coupled with its large Stokes shift, enables accurate quantification of Cys in real food samples and facilitates imaging for monitoring both exogenous and endogenous Cys levels in living cells.

Irisin Protects Musculoskeletal Homeostasis via a Mitochondrial Quality Control Mechanism.

Irisin, a myokine derived from fibronectin type III domain-containing 5 (FNDC5), is increasingly recognized for its protective role in musculoskeletal health through the modulation of mitochondrial quality control. This review synthesizes the current understanding of irisin's impact on mitochondrial biogenesis, dynamics, and autophagy in skeletal muscle, elucidating its capacity to bolster muscle strength, endurance, and resilience against oxidative-stress-induced muscle atrophy. The multifunctional nature of irisin extends to bone metabolism, where it promotes osteoblast proliferation and differentiation, offering a potential intervention for osteoporosis and other musculoskeletal disorders. Mitochondrial quality control is vital for cellular metabolism, particularly in energy-demanding tissues. Irisin's influence on this process is highlighted, suggesting its integral role in maintaining cellular homeostasis. The review also touches upon the regulatory mechanisms of irisin secretion, predominantly induced by exercise, and its systemic effects as an endocrine factor. While the therapeutic potential of irisin is promising, the need for standardized measurement techniques and further elucidation of its mechanisms in humans is acknowledged. The collective findings underscore the burgeoning interest in irisin as a keystone in musculoskeletal health and a candidate for future therapeutic strategies.

Efficacy and Safety of C3 Laminectomy Combined with Open-Door Laminoplasty versus Open-Door Laminoplasty Alone: A Systematic Review and Meta-Analysis.

BACKGROUND: To evaluate efficacy and safety between C3 laminectomy + open-door laminoplasty and open-door laminoplasty alone. METHODS: Electronic databases were systematically searched up to January 2024. Review Manager 5.4 was applied to manage the data and perform the review. Cochrane Library, PubMed, OVID, and Web of Science were searched for studies comparing C3 laminectomy + open-door laminoplasty and open-door laminoplasty alone. Forest plots were constructed for each analysis group. RESULTS: After selection, 9 eligible articles included 10 comparison groups, with a combined 320 patients who underwent C3 laminectomy + open-door laminoplasty and 355 who underwent open-door laminoplasty alone. There was no difference in operative time, blood volume, Japanese Orthopaedic Association score, Japanese Orthopaedic Association recovery score, visual analog scale score, Neck Disability Index, complications, axial symptoms, T1 slope, range of motion, and cervical sagittal vertical axis. C3 laminectomy + open-door laminoplasty was superior in C2-C7 Cobb angle. CONCLUSIONS: Although C3 laminectomy + open-door laminoplasty has theoretic advantages, meta-analysis results show that the 2 surgical procedures are similar in terms of clinical symptoms improvement, sagittal balance, and complications. C3 laminectomy combined + open-door laminoplasty is superior only in the preservation of cervical lordosis. The limited number of studies may affect the reliability and generalizability of the results. Future high-quality, multicenter randomized controlled trials are needed to verify efficacy and safety.

21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer.

PURPOSE: To assess the predictive value of the 21-gene recurrence score (RS) on the survival outcomes of postoperative radiotherapy (PORT) in elderly patients with T1N0 luminal breast cancer after breast-conserving surgery. METHODS: We retrospectively included patients aged ≥ 70 years and diagnosed with T1N0 luminal BC between 2004 and 2015 using the data from the Surveillance, Epidemiology, and End Results. The RS groups were categorized using the TAILORx criteria as follows: low risk (RS < 11) (LR), intermediate risk (RS 11-25) (IR), and high risk (RS > 25) (HR). Kaplan-Meier analysis, propensity score matching (PSM), and Cox proportional hazards analysis were used for statistical analysis. RESULTS: We included 5901 patients in the analysis. Of the patients, 4492 (76.1%) underwent PORT, while 1409 (23.9%) did not receive PORT. There were 1588 (26.9%), 3613 (61.2%), and 700 (12.0%) patients classified as LR, IR, and HR, respectively. There were 1182 (74.4%), 2773 (76.8%), and 537 (76.7%) patients in the LR, IR, and HR groups receiving PORT, respectively (P = 0.182). A total of 1353 pairs of patients were completely matched using PSM. PORT was independently associated with better overall survival (OS) (P < 0.001) and breast cancer-specific survival (BCSS) (P = 0.015) in the entire cohort. The sensitivity analyses showed that the receipt of PORT was not associated with OS (P = 0.887) and BCSS (P = 0.861) in the LR group. However, the receipt of PORT was associated with OS (P < 0.001) and BCSS in the IRHR group (P = 0.026). CONCLUSION: Our study highlights the possible role of the 21-gene RS in predicting the survival outcomes of PORT following BCS in elderly patients with T1N0 luminal breast cancer.

Optimized personalized management approach for moderate/severe OHSS: development and prospective validation of an OHSS risk assessment index.

STUDY QUESTION: Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS? SUMMARY ANSWER: This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts. WHAT IS KNOWN ALREADY: An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required. STUDY DESIGN, SIZE, DURATION: This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled. MAIN RESULTS AND THE ROLE OF CHANCE: We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort. LIMITATIONS, REASONS FOR CAUTION: The influence from clinical interventions including cryopreservation of all embryos cannot be eliminated and thus certain risk factors like estrogen level on trigger day might be assigned with a lower risk score. Another weakness of the study is that several preventive treatments, for instance oral aspirin and letrozole, were not recorded and evaluated in the model. Despite the robust reliability of OHSS assessment index, this tool cannot be used directly for clinical decision-making or as a diagnostic tool. Its value lies in its capacity to evaluate the prognosis of various interventions and to facilitate clinician-patient communication. The combination of this tool and further symptoms and examinations should be all taken into consideration for accurate and personalized management of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: The OHSS risk assessment index can be implemented to facilitate personalized counseling and management of OHSS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by National Key R&D Program of China (2022YFC2702504), Medical Research Fund Guangdong Provincial (A2024003), and Xinjiang Support Rural Science and Technology (Special Correspondent) Program in Guangdong Province (KTPYJ 2023014). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Induced pluripotent stem cell-derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis.

Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue-derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

Effect and mechanism of Lycium barbarum polysaccharide on gastrointestinal motility in slow transit constipation.

Slow transit constipation (STC) seriously affects the physical and mental health of patients. While the active ingredients of traditional Chinese medicine (TCM) are widely used in the treatment of STC due to their low toxicity and side effects, the aim of this study was to investigate the effect of Lycium barbarum polysaccharide (LBP) on STC. The STC mouse model was induced by the compound diphenoxylate. Defecation, fecal moisture, and weight loss of the STC models were monitored. Gastrointestinal (GI) motility was assessed by intestinal propulsive rate, and enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the levels of substance P (SP) and vasoactive intestinal peptide (VIP). The expression levels of inflammatory cytokines (Tnf-α, Il-6, and Il-1ß), stem cell factor receptor (C-kit), stem cell factor (Scf), Bcl-2, Bax, and Caspase-3 were evaluated by qRT-PCR. The defecation, fecal moisture, and body weight of mice with STC were significantly improved by LBP, and LBP increased the intestinal propulsive rate of STC, increased the secretion of SP, and decreased the secretion of VIP. The intervention of LBP further suppressed the expression levels of Tnf-α, Il-6, and Il-1ß in STC. LBP promoted the expression of the C-kit, Scf, and Bcl-2 and inhibited the expression of Bax and Caspase-3. LBP may alleviate symptoms of slow transit constipation (STC) and enhance gastrointestinal motility by modulating gastrointestinal hormone levels, promoting proliferation, and inhibiting the apoptosis of interstitial cells of Cajal (ICCs).

PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation mediated gene expression.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (PDH, E1), leaving other post-translational modifications (PTMs) largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma (HCC), disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein (E3BP) in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (DLAT, E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during HCC progression and providing a potential biomarker and therapeutic target for further development.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Nsun2 is critical for mouse oocyte meiosis and early embryonic development.

Biallelic variants in the NSUN2 gene cause a rare intellectual disability and female infertility in humans. However, the function and mechanism of NSUN2 during mouse oocyte meiotic maturation and early embryonic development are unknown. Here, we show that NSUN2 is important for mouse oocyte meiotic maturation and early embryonic development. Specifically, NSUN2 is required for ovarian development and oocyte meiosis, and deletion of Nsun2 reduces oocyte maturation and increases the rates of misaligned chromosomes and aberrant spindles. In addition, Nsun2 deficiency results in a low blastocyst rate and impaired blastocyst quality. Strikingly, loss of Nsun2 leads to approximately 35% of embryos being blocked at the 2-cell stage, and Nsun2 knockdown impairs zygotic genome activation at the 2-cell stage. Taken together, these findings suggest that NSUN2 plays a critical role in mouse oocyte meiotic maturation and early embryonic development, and provide key resources for elucidating female infertility with NSUN2 mutations.

A clinical prognostic model related to T cells based on machine learning for predicting the prognosis and immune response of ovarian cancer.

Background: Ovarian cancer (OV) is regarded as one of the most lethal malignancies affecting the female reproductive system, with individuals diagnosed with OV often facing a dismal prognosis due to resistance to chemotherapy and the presence of an immunosuppressive environment. T cells serve as a crucial mediator for immune surveillance and cancer elimination. This study aims to analyze the mechanism of T cell-associated markers in OV and create a prognostic model for clinical use in enhancing outcomes for OV patients. Methods: Based on the single-cell dataset GSE184880, this study used single-cell data analysis to identify characteristic T cell subsets. Analysis of high dimensional weighted gene co-expression network analysis (hdWGCNA) is utilized to identify crucial gene modules along with their corresponding hub genes. A grand total of 113 predictive models were formed utilizing ten distinct machine learning algorithms along with the combination of the cancer genome atlas (TCGA)-OV dataset and the GSE140082 dataset. The most dependable clinical prognostic model was created utilizing the leave one out cross validation (LOOCV) framework. The validation process for the models was achieved by conducting survival curve analysis and receiver operating characteristic (ROC) analysis. The relationship between risk scores and immune cells was explored through the utilization of the Cibersort algorithm. Additionally, an analysis of drug sensitivity was carried out to anticipate chemotherapy responses across various risk groups. The genes implicated in the model were authenticated utilizing qRT-PCR, cell viability experiments, and EdU assay. Results: This study developed a clinical prognostic model that includes ten risk genes. The results obtained from the training set of the study indicate that patients classified in the low-risk group experience a significant survival advantage compared to those in the high-risk group. The ROC analysis demonstrates that the model holds significant clinical utility. These results were verified using an independent dataset, strengthening the model's precision and dependability. The risk assessment provided by the model also serves as an independent prognostic factor for OV patients. The study also unveiled a noteworthy relationship between the risk scores calculated by the model and various immune cells, suggesting that the model may potentially serve as a valuable tool in forecasting responses to both immune therapy and chemotherapy in ovarian cancer patients. Notably, experimental evidence suggests that PFN1, one of the genes included in the model, is upregulated in human OV cell lines and has the capacity to promote cancer progression in in vitro models. Conclusion: We have created an accurate and dependable clinical prognostic model for OV capable of predicting clinical outcomes and categorizing patients. This model effectively forecasts responses to both immune therapy and chemotherapy. By regulating the immune microenvironment and targeting the key gene PFN1, it may improve the prognosis for high-risk patients.

Global Tendencies and Frontier Topics in Cervical Laminoplasty: A Bibliometric Analysis from 1982 to 2023.

BACKGROUND: This bibliometric analysis aimed to map the knowledge network of laminoplasty research. METHODS: Studies on laminoplasty published from 1982 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). The contributions of countries, institutions, authors, and journals were identified using VOSviewer, Scimago Graphica, and Microsoft Excel. Tendencies, hotspots, and knowledge networks were analyzed and visualized using VOSviewer and CiteSpace. RESULTS: We identified 2577 publications on laminoplasty. The annual number of publications exhibited an overall increasing trend since 2004. Among these, Japan, China, and the United States were the 3 major contributing countries. Keio University, Nagoya University, and Tokyo Medical & Dental University were the 3 most productive institutions. Shiro Imagama ranked first among authors regarding the number of articles, while K Hirabayashi was first among co-cited authors. Spine was the top journal in terms of the number of publications, citations, and co-citations. In addition, the research topics can be divided into 3 clusters: (1) Comparison between laminoplasty and other surgery in outcomes and complications; (2) Axial symptoms in laminoplasty; (3) Sagittal alignment and sagittal balance in laminoplasty. Emerging topics sagittal alignment and sagittal balance in degenerative cervical spondylosis are identified as current research frontiers. CONCLUSIONS: This study drew a knowledge map of the top countries, institutions, authors, publications, and journals on laminoplasty over the past 4 decades. The current and future hotspots of laminoplasty focus on sagittal balance, comparison between other surgery in outcomes and complication, and axial symptoms in laminoplasty.

Niraparib plays synergistic antitumor effects with NRT in a mouse ovarian cancer model with HRP.

OBJECTIVE: PARPi offers less clinical benefit for HRP patients compared to HRD patients. PARPi has an immunomodulatory function. NRT therapy targets tumor neoantigens without off-target immune toxicity. We explored the synergy between Niraparib and NRT in enhancing antitumor activity in an HRP ovarian cancer mouse model. METHODS: In the C57BL/6 mouse ID8 ovarian cancer model, the effect of Niraparib on reshaping TIME was evaluated by immune cell infiltration analysis of transcriptomic data. The antitumor effects of Niraparib, NRT, and their combined use were systematically evaluated. To corroborate alterations in TILs, TAMs, and chemokine profiles within the TIME, we employed immunofluorescence imaging and transcriptome sequencing analysis. RESULTS: Niraparib increased the M1-TAMs and activated CD8+ T cells in tumor tissues of C57BL/6 mice with ID8 ovarian cancer. GSEA showed that gene set associated with immature DC and INFα, cytokines and chemokines were significantly enriched in immune feature, KEGG and GO gene sets, meanwhile CCL5, CXCL9 and CXCL10 play dominant roles together. In the animal trials, combined group had a tumor growth delay compared with Niraparib group (P < 0.01) and control group (P < 0.001), and longer survival compared with the single agent group (P<0.01) . CONCLUSIONS: Niraparib could exert immune-reshaping effects, then acts synergistic antitumor effects with NRT in HRP ovarian cancer model. Our findings provide new ideas and rationale for combined immunotherapy in HRP ovarian cancer.