Elucidating the molecular mechanisms behind the therapeutic impact of median nerve stimulation on cognitive dysfunction post-traumatic brain injury.

OBJECTIVE: Ferroptosis represents a form of regulated cellular death dependent upon iron and lipid peroxidation derivatives, holding considerable implications for cerebral and neurologic pathologies. In the present study, we endeavored to elucidate the molecular mechanisms governing ferroptosis and appraise the therapeutic value of electrical stimulation of median nerve in addressing cognitive impairments following traumatic brain injury (TBI), employing a rodent model. METHODS: In this study, we established a rat model to investigate the cognitive impairments resulting from TBI, followed by the application of median nerve stimulation (MNS). Initially, rats received an intraperitoneal injection of Erastin (2 mg/kg) prior to undergoing MNS. After 24 h of MNS treatment, the rats were subjected to an open field test to evaluate their cognitive and motor functions. Subsequently, we conducted biochemical assays to measure the serum levels of GSH, MDA and SOD. The structural integrity and cellular morphology of hippocampal tissue were examined through H&E staining, Nissl staining and transmission electron microscopy. Additionally, we assessed the expression levels of proteins crucial for neuronal health and function in the hippocampus, including VEGF, SLC7A11, GPX4, Nrf2, α-syn, NEUN and PSD95. RESULTS: Compared to the control group, rats in the stimulation group demonstrated enhanced mobility, reduced levels of tissue damage, a decrease in MDA concentration, and increased levels of GSH and SOD. Additionally, there was a significant upregulation in the expression of proteins critical for cellular defense and neuronal health, including GPX4, SLC7A11, Nrf2, VEGF, α-syn, NEUN, and PSD95 proteins. Conversely, rats in the Erastin group demonstrated decreased mobility, exacerbated pathological tissue damage, elevated MDA concentration, and decreased levels of GSH and SOD. There was also a notable decrease in the expression of GPX4, SLC7CA11, Nrf2, and VEGF proteins. The expression levels of α-syn, NEUN, and PSD95 were similarly diminished in the Erastin group. Each of these findings was statistically significant, indicating that MNS exerts neuroprotective effect in the hippocampal tissue of rats with TBI by inhibiting the ferroptosis pathway. CONCLUSION: (1) MNS may enhance the cognitive and behavioral performance of rats after TBI; (2) MNS can play a neuroprotective role by promoting the expression of nerve injury-related proteins, alleviating oxidative stress and ferroptosis process; (3) MNS may inhibit ferroptosis of neuronal cells by activating Nrf2/ GPX4 signaling pathway, thereby improving cognitive impairment in TBI rats.

Light-induced ß-hydroxy sulfone synthesis in DNA-encoded libraries.

We here describe a visible-light photooxidation of sulfinate salts with common alkenes to yield ß-hydroxy sulfones on DNA. This process demonstrates a broad substrate compatibility and achieves conversion rates ranging from moderate to excellent. Most importantly, it presents a straightforward, efficient, and metal-free approach for synthesizing Csp3-rich DNA-encoded libraries.

Co-occurrence of ST412 Klebsiella pneumoniae isolates with hypermucoviscous and non-mucoviscous phenotypes in a short-term hospitalized patient.

Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism. IMPORTANCE: K. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

An Unexpected Synthesis of 2-Sulfonylquinolines via Deoxygenative C2-Sulfonylation of Quinoline N-Oxides with Sulfonyl Chlorides.

A mild, efficient and practical protocol for the preparation of 2-sulfonylquinolines through CS2/Et2NH-induced deoxygenative C2-H sulfonylation of quinoline N-oxides with readily available RSO2Cl was developed. The reaction proceeded well under transition-metal-free conditions and exhibited a wide substrate scope and functional group tolerance. The preliminary studies suggested that the nucleophilic sulfonyl sources were generated in situ via the reaction of CS2, Et2NH and sulfonyl chlorides.

Ts2O mediated deoxygenative C2-dithiocarbamation of quinoline N-oxides with CS2 and amines.

A general, efficient and practical protocol for Ts2O promoted deoxygenative dithiocarbamation of quinoline N-oxides with in situ generated dithiocarbamic acids from CS2 and amines is reported. The reaction proceeded well under transition-metal free conditions to obtain a variety of novel quinoline-dithiocarbamate compounds with wide functional group tolerance and good to high yields.

The Impact of Comprehensive Nursing and Warming Measures on Emergence Agitation and Maternal-Neonatal Safety in Women Undergoing General Anesthesia for Cesarean Section.

Objective: To explore the effects of comprehensive nursing combined with thermal insulation measures on the awakening agitation (EA) of cesarean section parturient under general anesthesia and maternal and infant safety. Methods: A total of 136 cesarean section parturients under general anesthesia admitted in our hospital from May 2020 to November 2023 were picked as the research objects following the random, double-blind method. All patients have no mental illness and can clearly reflect their physical state. The subjects were randomized into the study group and the control group in accordance with the random number table method, with 68 cases in each group. The control group was intervened with thermal insulation measures, while the study group was intervened with comprehensive nursing combined with thermal insulation measures. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) at different time points were compared. The Ramsay score (RASS), the incidence of EA, and the incidence of shivering were compared. The influence of comprehensive nursing combined with thermal insulation measures on maternal and infant safety and their recovery after the operation was analyzed. The adverse psychological status and postoperative satisfaction of the two groups were statistically analyzed. Results: SBP, DBP, and MAP in the study group were much higher than those in the control group at the time of skin incision, fetal delivery, and the end of operation (P < .05). Compared with the control group, the study group had much higher RASS, and sharply reduced incidence of EA and shivering (P < .05). The incidence of fetal distress, postpartum hemorrhage, neonatal asphyxia, etc., was significantly lower in the study group than in the control group P < .05). Parturient of the study group had a shorter duration of hospitalization, shorter detention time in the anesthesia monitoring room, and awakening time than the parturient in the control group (P < .05). The SAS and SDS scores of parturient were significantly decreased in the two groups at discharge than before the operation, and a more obvious decrease was found in the study group (P < .01). Postoperative satisfaction of the study group and the control group was 98.53% and 80.88%, respectively, which was markedly higher in the study group than in the control group (P < .05). Conclusion: Comprehensive nursing combined with thermal insulation measures vastly improved the sedation degree of parturient, reduced the incidence of EA and chills, ensured maternal and infant safety, reduced adverse pregnancy outcomes, promoted early recovery of parturient, and enhanced maternal satisfaction. This conclusion provides important guidance for improving clinical practice, emphasizing the key role of comprehensive care in improving surgical outcomes and patient comfort, thereby improving the quality and efficiency of medical services.

Impact of Comorbidities and Drug Interactions in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Androgen Receptor Pathway Inhibitors.

PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described. METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley's databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed. RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P = .04) and poorer overall survival (28 v 45 months, P = .04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences. CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes.

Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.

Gliomas are highly vascularized malignancies, but current anti-angiogenic treatments have not demonstrated practical improvements in patient survival. Studies have suggested that glioma-derived endothelial cell (GdEC) formed by glioma stem cell (GSC) differentiation may contribute to the failure of this treatment. However, the molecular mechanisms involved in GSC endothelial differentiation remain poorly understood. We previously reported that vasorin (VASN) is highly expressed in glioma and promotes angiogenesis. Here, we show that VASN expression positively correlates with GdEC signatures in glioma patients. VASN promotes the endothelial differentiation capacity of GSC in vitro and participates in the formation of GSC-derived vessels in vivo. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) is a critical factor that mediates the regulation of VASN on GSC endothelial differentiation. Separation of cell chromatin fractionation and chromatin immunoprecipitation-sequencing analysis show that VASN interacts with Notch1 and co-translocates into the cell nuclei, where VASN binds to the VEGFR2 gene promoter to stimulate its transcription during the progression of GSC differentiation into GdEC. Together, these findings elucidate the role and mechanisms of VASN in promoting the endothelial differentiation of GSC and suggest VASN as a potential target for anti-angiogenic therapy based on intervention in GdEC formation in gliomas.

Innovative On-DNA Synthesis of Sulfides and Sulfoximines: Enriching the DEL Synthesis Toolbox.

DNA-encoded library (DEL) technologies enable the fast exploration of gigantic chemical space to identify ligands for the target protein of interest and have become a powerful hit finding tool for drug discovery projects. However, amenable DEL chemistry is restricted to a handful of reactions, limiting the creativity of drug hunters. Here, we describe a new on-DNA synthetic pathway to access sulfides and sulfoximines. These moieties, usually contemplated as challenging to achieve through alkylation and oxidation, can now be leveraged in routine DEL selection campaigns.

Can serum progesterone concentration direct a fresh or freeze-all transfer strategy in the first in vitro fertilisation cycle?

PURPOSE: To examine the interaction between serum progesterone concentration on the trigger day and choice of freeze-all and fresh transfer strategies on live birth in an unselected population as well as in patients over 35 years old. METHODS: We performed a retrospective cohort study of 26,661 patients commencing their first IVF cycle in a large fertility centre between 2015 and 2019, including 4687 patients over 35 years old. We performed a multivariable fractional polynomial interaction analysis within a logistic regression model to investigate the interaction between serum progesterone concentration and the choice of freeze-all or fresh transfer strategy following the first transfer. RESULTS: 15,539 patients underwent a fresh embryo transfer and 11,122 underwent a freeze-all strategy in their first IVF cycle. The freeze-all group had a higher live birth rate compared to the fresh group (43.9% vs 40.3%). After adjusting for confounding factors, there was a positive interaction between serum progesterone concentrations and the choice of a freeze-all versus fresh embryo transfer on live birth (p for interaction 0.0001), with a larger magnitude of effect when progesterone concentration was higher. Such an interaction was also observed in patients over 35 years old (p for interaction 0.01), but the treatment effect curve over progesterone concentrations was almost flat. CONCLUSIONS: In an unselected population, frozen transfer is associated with greater chances of live birth, especially in patients with higher serum progesterone concentration. In patients over 35 years old, the benefit of a freeze-all policy appears small across all serum progesterone concentrations.

Exploring efficient strategies for air quality improvement in China based on its regional characteristics and interannual evolution of PM2.5 pollution.

Fine particulate matter (PM2.5) harms human health and hinders normal human life. Considering the serious complexity and obvious regional characteristics of PM2.5 pollution, it is urgent to fill in the comprehensive overview of regional characteristics and interannual evolution of PM2.5. This review studied the PM2.5 pollution in six typical areas between 2014 and 2022 based on the data published by the Chinese government and nearly 120 relevant literature. We analyzed and compared the characteristics of interannual and quarterly changes of PM2.5 concentration. The Beijing-Tianjin-Hebei region (BTH), Yangtze River Delta (YRD) and Pearl River Delta (PRD) made remarkable progress in improving PM2.5 pollution, while Fenwei Plain (FWP), Sichuan Basin (SCB) and Northeast Plain (NEP) were slightly inferior mainly due to the relatively lower level of economic development. It was found that the annual average PM2.5 concentration change versus year curves in the three areas with better pollution control conditions can be merged into a smooth curve. Importantly, this can be fitted for the accurate evaluation of each area and provide reliable prediction of its future evolution. In addition, we analyzed the factors affecting the PM2.5 in each area and summarize the causes of air pollution in China. They included primary emission, secondary generation, regional transmission, as well as unfavorable air dispersion conditions. We also suggested that the PM2.5 pollution control should target specific industries and periods, and further research need to be carried out on the process of secondary production. The results provided useful assistance such as effect prediction and strategy guidance for PM2.5 pollution control in Chinese backward areas.

Impact of frailty on pneumonia outcomes in older patients: a systematic review and meta-analysis.

PURPOSE: The ideal method for identifying frailty remains unclear, but the condition is associated with poor prognoses in many illnesses. Despite the availability of studies, the prognostic implications of frailty on older patients with pneumonia remains unexplored. To determine the burden and effect of frailty on selected clinical outcomes among older patients with pneumonia. METHODS: We searched Medline, Google Scholar, and Science Direct databases for articles published in English following the PRISMA framework to guide our review. We included studies conducted on patients (> 60 years) with frailty and pneumonia, and reporting the effect of frailty on mortality, hospital stay, length readmission, and ICU admission. We performed a meta-analysis using STATA 14.2, calculating pooled odds ratios and 95% confidence intervals. RESULTS: We analysed data from 16 studies and calculated a pooled frailty prevalence of 49% (95% CI 37-60%) in older patients with pneumonia. Unadjusted analyses revealed an odds ratio (OR) of 2.50 (95% CI 1.88-3.32) for the intermediate risk group, and an OR of 3.51 (95% CI 3.05-4.05) for the high risk group regarding mortality. The high risk frailty group also exhibited significant elevations in the risk of readmissions and extended hospital stay lengths. Substantial heterogeneity was observed in both adjusted and unadjusted analyses. CONCLUSIONS: Our systematic review and meta-analysis results show that one in every two older individuals with pneumonia present frailty, a condition that significantly influences their rates of mortality and readmission, and their hospital stay length.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

A comprehensive review of bupleuri radix and its bioactive components： with a major focus on treating chronic liver diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

Efficient synthesis of SCF3-containing 3-alkenylquinoxalinones via three-component radical cascade reaction.

An efficient and practical method for the synthesis of 3-alkenylquinoxalinones containing the SCF3 group has been readily developed through a three-component radical cascade reaction involving quinoxalinones, alkynes and AgSCF3. The reaction was found to be compatible with a variety of substrates and exhibited a high functional group tolerance and complete E-selectivity. The preliminary study suggests the involvement of a SCF3 radical in the transformation.

Ts2O Promoted Deoxygenative C-H Dithiocarbonation of Quinoline N-Oxides with Potassium O-Alkyl Xanthates.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Efficient method for modeling large-scale arrays of optical nanoresonators based on the coupling theory of quasinormal mode.

We propose an efficient method for calculating the electromagnetic field of a large-scale array of optical nanoresonators based on the coupling theory of quasinormal mode (QNM). In this method, two approaches of the scattered-field reconstruction and stationary-phase-principle calculated plane-wave expansion are developed to obtain the regularized QNM (RQNM) in different regions. This accurate and efficient calculation of RQNM resolves the far-field divergence issue of QNMs in the QNM-coupling theory, thus enabling a rapid computation of the electromagnetic field of a large-scale array of optical nanoresonators, which is a challenging task for full-wave numerical methods. Using this method, we consider the numerical example of the radiation problem of a single point source in a large-scale periodic array of optical nanoantennas. In comparison to full-wave numerical methods, this method significantly reduces the computation time by 1∼2 orders of magnitude while maintaining accuracy. The high computational efficiency and physical intuitiveness of the method enables to clarify the impact of array size (exceeding 50 × 50 wavelengths), period and field-coupling range (far beyond the tight-binding approximation) on the optical response. The proposed method and results can provide an efficient tool and guidance for the design of large-scale arrays of optical nanoresonators.

Evaluation the relationship between myocardial fibrosis and left ventricular torsion measured by cardiac magnetic resonance feature-tracking in hypertrophic cardiomyopathy patients with preserved ejection fraction.

The relationship between left ventricular (LV) torsion and myocardial fibrosis (MF) in hypertrophic cardiomyopathy (HCM) patients with preserved ejection fraction was still not well understood. New developments in cardiac magnetic resonance (CMR) enable a much fuller assessment of cardiac characteristics. This study sought to assess the impact of HCM on myocardial function as assessed by LV torsion and its relationship with MF. HCM (n = 79) and healthy controls (n = 40) underwent CMR. According to whether there was late gadolinium enhancement (LGE), patients were divided into LGE+ group and LGE- group. LV torsion and torsion rate were measured by CMR feature-tracking (CMR-FT). MF was quantitatively evaluated through LGE imaging. LGE was present in 44 patients (56%). Compared with healthy controls, torsion increased in the LGE- group (P < 0.001). Compared with LGE+ group, torsion was higher in the LGE- group (P < 0.001). There was no significant difference in torsion between LGE+ group and healthy controls. Correlation analysis showed that torsion was correlated with LGE% (r = - 0.443) and LGE mass (r = - 0.435) respectively. On multivariable logistic regression analysis, LV torsion was the only feature that was independently associated with the presence of LGE (OR 0.130; 95% CI 0.040 to 0.420, P = 0.01). The best torsion value associated with MF was 1.91 (sensitivity 60.0%, specificity 77.3%, AUC = 0.733). In HCM patients with preserved ejection fraction, CMR-FT derived LV torsion analysis holds promise for myocardial fibrosis detection.

Immediate Effect of Electro-acupuncture on Endometrial Blood Flow in Patients with Recurrent Implantation Failure: A Randomized Controlled Trial.

OBJECTIVE: To investigate the immediate effects of electro-acupuncture (EA) on endometrial blood flow among recurrent implantation failure (RIF) patients. METHODS: Eighty RIF patients, enrolled from March 2022 to December 2022, were randomly allocated into either the EA group (40 cases) or the waiting-list (WL) group (40 cases) by using a random number table. The EA group underwent acupuncture at points of Shenting (GV 24), Baihui (GV 4), Benshen (GB 13), bilateral Zigong (EX-CA 1), Huangshu (KI 16), Sanyinjiao (SP 6) and Xuehai (SP10), and electric acupuncture apparatus was connected to EX-CA 1, KI 16, SP 6, and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound, while the WL group received no intervention. The primary outcome measured was the endometrial volume blood flow. The secondary outcomes included the bilateral uterine artery index, endometrial volume, endometrial blood flow type, vascular distribution index (VIMV) for endometrial and ovary, clinical pregnancy rate, and embryo implantation rate. RESULTS: In the EA group, there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA (P<0.05). Both the endometrial blood flow type and VIMV for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment (P<0.05). Conversely, no significant disparities were observed in vascular index, flow index, vascular blood flow index, uterine arterial blood flow indices, endometrial volume, clinical pregnancy rate and embryo implantation rate between the two groups after treatment (P>0.05). Besides, no adverse events related to EA were observed. CONCLUSIONS: EA can promptly ameliorate VIMV for the endometrial and right ovary, and endometrial blood flow type. Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes. (Trial registration No. ChiCTR2200057377).

Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hEC) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. IMPLICATIONS: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.