Bound-Extended Mode Transition in Type-II Synthetic Photonic Weyl Heterostructures.

Photonic structures with Weyl points (WPs), including type I and type II, promise nontrivial surface modes and intriguing light manipulations for their three-dimensional topological bands. While previous studies mainly focus on exploring WPs in a uniform Weyl structure, here we establish Weyl heterostructures (i.e., a nonuniform Weyl lattice) with different rotational orientations in the synthetic dimension by nanostructured photonic waveguides. In this work, we unveil a transition between bound and extended modes on the interface of type-II Weyl heterostructures by tuning their rotational phases, despite the reversed topological order across the interface. This mode transition is also manifested from the total transmission to total reflection at the interface. All of these unconventional effects are attributed to the tilted dispersion of type-II Weyl band structure that can lead to mismatched bands and gaps across the interface. As a comparison, the type-I Weyl heterostructures lack the phase transition due to the untilted band structure. This work establishes a flexible scheme of artificial Weyl heterostructures that opens a new avenue toward high-dimensional topological effects and significantly enhances our capabilities in on-chip light manipulations.

Multidimensional features of sporadic Creutzfeldt-Jakob disease in the elderly: a case report and systematic review.

Background: As a rare neurodegenerative disease, sporadic Creutzfeldt-Jakob disease (sCJD) is poorly understood in the elderly populace. This study aims to enunciate the multidimensional features of sCJD in this group. Methods: A case of probable sCJD was reported in a 90-year-old Chinese man with initial dizziness. Then, available English literature of the elderly sCJD cases (aged 80 years and over) was reviewed and analyzed. Patients (15 cases) were subdivided and compared geographically. Results: In the elderly sCJD cohort, the onset age was 84.9 ± 4.5 years and the median disease duration was 6.8 months, with respiratory infection/failure as the commonest death cause. Various clinical symptoms were identified, with cognitive disorder (86.7%) as the commonest typical symptom and speech impairment (66.7%) as the most atypical one. Restricted hyperintensities were reported in 60.0% cases on DWI, periodic sharp wave complexes in 73.3% cases on electroencephalogram, and cerebral hypoperfusion/hypometabolism in 26.7% cases on molecular imaging. The sensitive cerebrospinal fluid biomarkers were total tau (83.3%), 14-3-3 protein (75.0%), and PrP RT-QuIC (75.0%). Neuropathological profiles in the cerebral cortex revealed vacuolar spongiosis, neuronal loss, gliosis, and aging-related markers, with synaptic deposit as the commonest PrP pattern (60.0%). The polymorphic PRNP analysis at codon 129 was M/M (90.9%), with MM1 and MM2C as the primary molecular phenotypes. Latency to first clinic visit, hyperintense signals on DWI, and disease duration were significantly different between the patient subgroups. Conclusion: The characteristics of sCJD are multidimensional in the elderly, deepening our understanding of the disease and facilitating an earlier recognition and better care for this group.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study.

STUDY QUESTION: Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage? SUMMARY ANSWER: In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages. WHAT IS KNOWN ALREADY: Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear. STUDY DESIGN SIZE DURATION: The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417 580), vitamin D deficiency (426 cases and 354 812 controls), miscarriage (16 906 cases and 149 622 controls), and the number of miscarriages (n = 78 700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis. PARTICIPANTS/MATERIALS SETTING METHODS: This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P = 0.927), or the number of miscarriages (ß = -0.004, 95% CI: -0.040 to 0.032, P = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P = 0.624), or the number of miscarriages (ß = 0.001, 95% CI: -0.009 to 0.011, P = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found. LIMITATIONS REASONS FOR CAUTION: This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS: These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage. STUDY FUNDING/COMPETING INTERESTS: This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research & Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure.

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8+ T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4+ T cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4+ T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. Inhibiting TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The anti-tumoral effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes an anti-tumoral role of the Tfh-dependent TLS in the development of LUAD.

Comparative efficacy and safety between endoscopic submucosal dissection, surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.

Platelet Membrane Biomimetic Manganese Carbonate Nanoparticles Promote Breast Cancer Stem Cell Clearance for Sensitized Radiotherapy.

Introduction: The presence of cancer stem cells (CSCs) significantly limits the therapeutic efficacy of radiotherapy (RT). Efficient elimination of potential CSCs is crucial for enhancing the effectiveness of RT. Methods: In this study, we developed a biomimetic hybrid nano-system (PMC) composed of MnCO3 as the inner core and platelet membrane (PM) as the outer shell. By exploiting the specific recognition properties of membrane surface proteins, PMC enables precise targeting of CSCs. Sonodynamic therapy (SDT) was employed using manganese carbonate nanoparticles (MnCO3 NPs), which generate abundant reactive oxygen species (ROS) upon ultrasound (US) irradiation, thereby impairing CSC self-renewal capacity and eradicating CSCs. Subsequent RT effectively eliminates common tumor cells. Results: Both in vitro cell experiments and in vivo animal studies demonstrate that SDT mediated by PMC synergistically enhances RT to selectively combat CSCs while inhibiting tumor growth without noticeable side effects. Discussion: Our findings offer novel insights for enhancing the efficacy and safety profiles of RT.

Perfect Excitation of Topological States by Supersymmetric Waveguides.

Topological photonic states provide intriguing strategies for robust light manipulations, however, it remains challenging to perfectly excite these topological eigenstates due to their complicated mode profiles. In this work, we propose to realize the exact eigenmode of the topological edge states by supersymmetric (SUSY) structures. By adiabatically transforming the SUSY partner to its main topological structure, the edge modes can be perfectly excited with simple single-site input. We experimentally verify our strategy in integrated silicon waveguides in telecommunication wavelength, showing a broad working bandwidth. Moreover, a shortcut-to-adiabaticity strategy is further applied to speed up the adiabatic pump process by inverse-design approaches, thus enabling fast mode evolutions and leading to reduced device size. Our method is universal and beneficial to the topology-based or complex eigenmodes systems, ranging from photonics and microwaves to cold atoms and acoustics.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

A pyroptosis-related gene expression signature predicts immune microenvironment and prognosis in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive malignancy with a poor prognosis. Pyroptosis triggered by gasdermins family proteins is reported vital for tumor microenvironment and cancer progression. However, pyroptosis-related gene expression and its relationship with immune infiltration and prognosis of HNSCC have not been fully defined. MATERIAL AND METHODS: RNA-sequencing data of HNSCC patients were acquired from The Cancer Genome Atlas (TCGA) database. A pyroptosis-related gene expression signature and infiltrated immune cells were analyzed. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and nomogram analyses were used to construct a clinical-molecular risk model for survival prognosis. RESULTS: HNSCC was classified into three different molecular subtypes based on the expression information of pyroptosis-related genes. Immune cell infiltration was demonstrated to be distinct between the three subtypes. The segregation of patients into the high-risk group and low-risk group, were carried out using the signature of differential expression genes (DEGs) signature among the three molecular subtypes. The precision of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the 3-year area under time-dependent ROC curve (AUC) reaching 0.711. The risk model was validated in another dataset from the Gene Expression Omnibus (GEO) database. Subsequently we established a clinical-molecular nomogram which combined the risk score with age and stage. The calibration plots for predicting the overall survival rate of 1-, 3-, and 5-years indicated that the nomogram performs well. CONCLUSION: The expression signature that encompasses pyroptosis-related genes could be used as molecular classification for HNSCC and pyroptosis might be a promising therapeutic target in HNSCC.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

A novel and independent survival prognostic model for OSCC: the functions and prognostic values of RNA-binding proteins.

BACKGROUND: Oral squamous cell carcinoma (OSCC), exhibiting high morbidity and malignancy, is the most common type of oral cancer. The abnormal expression of RNA-binding proteins (RBPs) plays important roles in the occurrence and progression of cancer. The objective of the present study was to establish a prognostic assessment model of RBPs and to evaluate the prognosis of OSCC patients. METHODS: Gene expression data in The Cancer Genome Atlas (TCGA) were analyzed by univariate Cox regression analysis model that established a novel nine RBPs, which were used to build a prognostic risk model. A multivariate Cox proportional regression model and the survival analysis were used to evaluate the prognostic risk model. Moreover, the receive operator curve (ROC) analysis was tested further the efficiency of prognostic risk model based on data from TCGA database and Gene Expression Omnibus (GEO). RESULTS: Nine RBPs' signatures (ACO1, G3BP1, NMD3, RNGTT, ZNF385A, SARS, CARS2, YARS and SMAD6) with prognostic value were identified in OSCC patients. Subsequently, the patients were further categorized into high-risk group and low-risk in the overall survival (OS) and disease-free survival (DFS), and external validation dataset. ROC analysis was significant for both the TCGA and GEO. Moreover, GSEA revealed that patients in the high-risk group significantly enriched in many critical pathways correlated with tumorigenesis than the low, including cell cycle, adheres junctions, oocyte meiosis, spliceosome, ERBB signaling pathway and ubiquitin-mediated proteolysis. CONCLUSIONS: Collectively, we developed and validated a novel robust nine RBPs for OSCC prognosis prediction. The nine RBPs could serve as an independent and reliable prognostic biomarker and guiding clinical therapy for OSCC patients.

Effects of Cold Rolling or Precipitation Hardening Treatment on the Microstructure, Mechanical Properties, and Corrosion Resistance of Ti-Rich Metastable Medium-Entropy Alloys.

Titanium-rich metastable medium-entropy alloys, designed for low elastic moduli, sacrifice strength. However, enhancing their mechanical strength is crucial for bio-implant applications. This study aims to enhance the mechanical properties and corrosion resistance of a metastable Ti80-Nb10-Mo5-Sn5 medium-entropy alloy using various treatments, including cold rolling (at 50% and 75% reduction) and precipitation hardening (at room temperature, 150 °C, 350 °C, 550 °C, and 750 °C). The results showed that the alloy underwent a stress-induced martensitic transformation during the rolling process. Notably, the α phase was precipitated in the ß grain boundaries after 30 days of precipitation hardening at room temperature. The yield strengths of the alloy increased by 51% and 281.9% after room-temperature precipitation and 75% cold rolling, respectively. In potentiodynamic corrosion tests conducted in phosphate-buffered saline solution, the pitting potentials of the alloy treated using various conditions were higher than 1.8 V, and no pitting holes were observed on the surface of the alloys. The surface oxide layer of the alloy was primarily composed of TiO2, Nb2O5, MoO3, and SnO2, contributing to the alloy's exceptional corrosion and pitting resistance. The 75% rolled Ti80-Nb10-Mo5-Sn5 demonstrates exceptional mechanical properties and high corrosion resistance, positioning it as a promising bio-implant candidate.

Intrauterine perfusion of dexamethasone improves pregnancy outcomes in recurrent reproductive failure patients with elevated uterine natural killer cells. A retrospective cohort study.

OBJECTIVE: To determine the effect of intrauterine perfusion of dexamethasone (DXM) on pregnancy outcomes in recurrent reproductive failure (RRF) patients with elevated uNK cells. METHODS: This retrospective cohort study included 132 RRF patients with elevated uNK cells: 56 patients received DXM treatment and 76 patients refused it in the frozen-thawed embryo transfer cycles. To determine the efficacy of intrauterine perfusion of DXM, multivariate logistic regression models and diagnosis-based subgroup analysis were performed. We also compared the pregnancy outcomes of patients with different responsiveness to DXM treatment. RESULTS: Intrauterine perfusion of DXM significantly improved clinical pregnancy rate (aOR: 3.188, 95% CI: 1.395-7.282, P = .006) and live birth rate (aOR: 3.176, 95% CI: 1.318-7.656, P = .010) in RRF patients with elevated uNK cells, but there was no significant association with miscarriage rate. Subgroup analysis revealed that intrauterine perfusion of DXM in patients with recurrent implantation failure (RIF) showed significant improvement in clinical pregnancy rate (aOR: 6.110, 95% CI: 1.511-24.713, P = .011) and live birth rate (aOR: 9.904, 95% CI: 1.963-49.968, P = .005), but there was insufficient evidence of benefit in recurrent pregnancy loss (RPL) patients. Additionally, uNK cell levels dropped to normal range was achieved in only 35.90% of RRF patients after DXM treatment, no significant difference was found in pregnancy outcomes among patients with different responsiveness to DXM treatment (all P > .05). CONCLUSION: Intrauterine perfusion of DXM was a promising and effective treatment to enhance clinical pregnancy rate and live birth rate in RRF women with abnormally elevated uNK cells, and RIF patients are more likely to benefit than RPL patients.

Platform for Quantitative Detection of Endometrial Immune Cells Based on Immunohistochemistry and Digital Image Analysis.

To evaluate the endometrial immune microenvironment of patients with recurrent miscarriage (RM), a digital immunohistochemistry image analysis platform was developed and validated to quantitatively analyze endometrial immune cells during the mid-luteal phase. All endometrium samples were collected during the mid-luteal phase of the menstrual cycle. Paraffin-embedded endometrial tissues were sectioned into 4 µm thick slides, and immunohistochemistry (IHC)staining was carried out for detecting endometrial immune cells, including CD56+ uNK cells, Foxp3+ Tregs, CD163+ M2 macrophages, CD1a+ DCs, and CD8+ T cells. The panoramic slides were scanned using a digital slide scanner and a commercial image analysis system was used for quantitative analysis. The percentage of endometrial immune cells was calculated by dividing the number of immune cells in the total endometrial cells. Using the commercial image analysis system, quantitative evaluation of endometrial immune cells, which are difficult or impossible to analyze with conventional image analysis, could be easily, and accurately analyzed. This methodology can be applied to quantitatively characterize the endometrium microenvironment, including interaction between immune cells, and its heterogeneity for different reproductive failure patients. The platform for quantitative evaluation of endometrial immune cells may be of important clinical significance for the diagnosis and treatment of RM patients.

A tumor cell exosome-mimicking multifunctional nanozyme for targeted breast cancer radiotherapy.

Radiotherapy (RT) has been extensively used for the treatment of breast cancer. However, the efficacy of RT is reduced by the high content of reducing species within cells (such as glutathione (GSH)). In addition, high-dose radiotherapy is often accompanied by serious side effects. In an attempt to resolve these issues, a tumor cell exosome-mimicking multifunctional nanozyme system (CuPy-Au@EM) was developed as a radiosensitizer, which consists of an internal AuNP-embedded CuPy nanozyme core and an external tumor cell exosome membrane. The exosome membrane protein on the surface of CuPy-Au@EM leads to the accurate localization of nano-materials in the tumor site; simultaneously, the level of H2O2 will be enhanced because of the GOx-like activity of AuNPs. Then CuPy-Au@EM would continue to trigger a rapid decline in cellular GSH content and the production of a large number of hydroxyl radicals (˙OH) through its glutathione peroxidase (GPx) and peroxidase (POD) activities allows for the extension of the radiotherapeutic cascade. Studies conducted in vivo and in vitro demonstrated that the combination of CuPy-Au@EM and moderate dose RT (4 Gy) can significantly reduce tumor proliferation. These findings indicated that CuPy-Au@EM nanospheres could be plausibly developed into promising radio-sensitizers on tumors.

Association between immunity and different clinical symptoms in patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a disease with endocrine and metabolic disorders. The main symptoms are hyperandrogenemia (HA), insulin resistance (IR), and ovulation disorder. However, the pathogenesis and pathophysiological process of these major symptoms in PCOS are still not well defined. In recent studies, the chronic low-grade inflammatory state has become one of the factors affecting PCOS. Some alterable immune factors in PCOS, such as interleukin-15 and interleukin-1, have been identified to be related to androgen synthesis and insulin resistance in PCOS. In addition, a disturbed immune microenvironment in the ovary leads to impaired follicular growth and ovulation. Previous studies have roughly reviewed the relationship between immunity and PCOS. However, the link between the different clinical manifestations of PCOS and immunity has not been well explored and analyzed. The clinical presentation of each patient is diverse, and symptomatic treatment is mainly used. Therefore, this article reviews several representative immunological factors that affect these three symptoms to explore the underlying mechanism, which will be beneficial for developing new treatment strategies.

Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response.

Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15+CD8+ T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15+CD8+ T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15+CD8+ T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15+CD8+ T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy.

The effectiveness and safety of intrauterine infusion of autologous regulatory T cells (Tregs) in patients with recurrent pregnancy loss and low levels of endometrial FoxP3+ cells: A retrospective cohort study.

PROBLEM: Regulatory T cells (Tregs) are a specialized type of T cells that help maintain immune tolerance and homeostasis. The potential of Tregs cell-based therapies in treating diseases has been demonstrated in several clinical trials, which have shown promising outcomes and high safety in autoimmune diseases, transplant rejection, and graft-versus-host disease. However, their effectiveness and safety in improving endometrial receptivity and reducing pregnancy loss in human reproduction are unknown. METHOD OF STUDY: The study used a retrospective design and included patients with recurrent pregnancy loss (RPL) and lower levels of endometrial FoxP3+ Tregs. Patients in the Tregs group (n = 33) received intrauterine Tregs infusion three times during the follicular phase, while the control group (n = 28) did not receive any intrauterine infusion. RESULTS: The intrauterine infusion of autologous Tregs increased the levels of FoxP3+ Tregs and CD56+ NK cells. Patients in the Treg group had higher live birth rates and lower miscarriage rates, especially early miscarriage rates. However, the two groups had no differences in the implantation rate, clinical pregnancy rate, and percentage of preterm delivery. CONCLUSIONS: The findings suggest that intrauterine Tregs infusion may be a potential therapeutic approach for RPL. Further research in larger clinical trials is needed to confirm these findings.

γδ-T cell with high toxic potential was associated with recurrent miscarriage.

PROBLEM: RM is a common clinical disease in reproduction, affecting approximately 1%-3% of women worldwide. Previous studies have shown the role of peripheral blood γδ-T cells during physiological pregnancy. However, the relationship between the immune status of peripheral blood γδ-T cells and RM is still not well defined. METHOD OF STUDY: In this study, mid-luteal peripheral blood from 51 RM patients and 40 healthy women was collected to determine the immune status of γδ-T cells. The percentage of peripheral blood γδ-T cells, and the molecules mediating their toxic potential, including cytotoxic granules (perforin, granzyme B, and granulysin) and receptors (NKG2D, CD158a, and CD158b), were detected by flow cytometry. RESULTS: Compared to healthy control, an increase in the proportion of total CD3+ T cells in lymphocytes and a decrease in the ratio of γδ-T cells to CD3+ T cells were observed in patients with RM. The percentages of granzyme B+ γδ-T cells and CD158a+ γδ-T cells in total γδ-T cells or lymphocytes were significantly increased in patients with RM, compared with healthy control. Conversely, CD158b+ γδ-T cells in total γδ-T cells or lymphocytes were significantly decreased in the RM group. CONCLUSION: Increased peripheral blood γδ-T cell with high toxic potential was associated with RM.