Mosunetuzumab for the treatment of follicular lymphoma.

INTRODUCTION: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that shows a progressive increase in relapses and refractory in its natural history and a median survival of approximately 18-20 years. The advent of anti-CD20 monoclonal antibodies has changed the FL therapeutic algorithm, with an increase in progression-free survival. T-cell-dependent bispecific antibodies (BsAbs) represent an emerging drug class against FL. AREAS COVERED: In this review, we selected papers from the principal databases (PubMed, Medline, Medscape, ASCO, ESMO) between January 2021 and June 2024, using the keywords 'mosunetuzumab' and 'follicular lymphoma' to provide an overview of mosunetuzumab-axgb, a pioneering BsAb. Its mechanism of action, efficacy, safety, and future perspectives were analyzed. EXPERT OPINION: Mosunetuzumab grants a directing T-cell mediated cytotoxicity and allows a step-up dosing that reduces adverse events, such as cytokine release syndrome, with promising tolerability. At the same time, it improves outcomes in the evolving landscape of FL management, even in post-CAR-T FL patients. Prognostic factors and targetable mechanisms of resistance need to be explored.

Long non-coding ribonucleic acid SNHG18 induced human granulosa cell apoptosis via disruption of glycolysis in ovarian aging.

BACKGROUND: In-depth understanding of dynamic expression profiles of human granulosa cells (GCs) during follicular development will contribute to the diagnostic and targeted interventions for female infertility. However, genome-scale analysis of long non-coding ribonucleic acid (lncRNA) in GCs across diverse developmental stages is challenging. Meanwhile, further research is needed to determine how aberrant lncRNA expression participates in ovarian diseases. METHODS: Granulosa cell-related lncRNAs data spanning five follicular development stages were retrieved and filtered from the NCBI dataset (GSE107746). Stage-specific lncRNA expression patterns and mRNA-lncRNA co-expression networks were identified with bioinformatic approaches. Subsequently, the expression pattern of SNHG18 was detected in GCs during ovarian aging. And SNHG18 siRNA or overexpression plasmids were transfected to SVOG cells in examining the regulatory roles of SNHG18 in GC proliferation and apoptosis. Moreover, whether PKCɛ/SNHG18 signaling take part in GC glycolysis via ENO1 were verified in SVOG cells. RESULTS: We demonstrated that GC-related lncRNAs were specifically expressed across different developmental stages, and coordinated crucial biological functions like mitotic cell cycle and metabolic processes in the folliculogenesis. Thereafter, we noticed a strong correlation of PRKCE and SNHG18 expression in our analysis. With downregulated SNHG18 of GCs identified in the context of ovarian aging, SNHG18 knockdown could further induce cell apoptosis, retard cell proliferation and exacerbate DNA damage in SVOG cell. Moreover, downregulated PKCɛ/SNHG18 pathway interrupted the SVOG cell glycolysis by lowering the ENO1 expression. CONCLUSIONS: Altogether, our results revealed that folliculogenesis-related lncRNA SNHG18 participated in the pathogenesis of ovarian aging, which may provide novel biomarkers for ovarian function and new insights for the infertility treatment.

Thyroid lesions in a population of domestic cats submitted to necropsy without clinical suspicion of thyroid disease.

Although hyperthyroidism is the most common endocrine disorder in elderly cats, systematic studies investigating the prevalence of thyroid lesions in feline animals are scarce. Our objective was to evaluate morphological changes in the thyroid glands of 61 cats submitted to necropsy without clinical suspicion of hyperthyroidism. Thirteen (13/61 [21.3%]) cats had thyroid enlargement and 54/61 (88.5%) had some histological thyroid changes. Proliferative lesions were histologically seen in 33/61 (54%) cats while non-proliferative lesions were observed in 48/61 (78.7%) cats. Thyroid hyperplasia (18/33 [54.5%]) and cystic adenoma (6/33 [18.2%]) were the most prevalent proliferative changes and lesions with little or no clinical significance (37/61 [60.6%]), degenerative (31/61 [50.8%]) and inflammatory changes (12/61 [19.7%]) were the most common non-proliferative changes. Among cats with proliferative lesions, 16/33 (48.4%) had a proliferation grade ≥A4, a grade previously associated with clinical hyperthyroidism. Although the cats from this study did not have any clinical diagnosis of thyroid disease, it is possible that one or more had some degree of clinically unnoticed thyroid dysfunction. The high prevalence of follicular lesions in this study highlights the importance of a more careful clinical and pathological investigation regarding thyroid diseases in mature and elderly cats.

Multi-Omics Reveals the Role of Arachidonic Acid Metabolism in the Gut-Follicle Axis for the Antral Follicular Development of Holstein Cows.

In vitro embryonic technology is crucial for improving farm animal reproduction but is hampered by the poor quality of oocytes and insufficient development potential. This study investigated the relationships among changes in the gut microbiota and metabolism, serum features, and the follicular fluid metabolome atlas. Correlation network maps were constructed to reveal how the metabolites affect follicular development by regulating gene expression in granulosa cells. The superovulation synchronization results showed that the number of follicle diameters from 4 to 8 mm, qualified oocyte number, cleavage, and blastocyst rates were improved in the dairy heifers (DH) compared with the non-lactating multiparous dairy cows (NDC) groups. The gut microbiota was decreased in Rikenellaceae_RC9_gut_group, Alistipes, and Bifidobacterium, but increased in Firmicutes, Cyanobacteria, Fibrobacterota, Desulfobacterota, and Verrucomicrobiota in the NDC group, which was highly associated with phospholipid-related metabolites of gut microbiota and serum. Metabolomic profiling of the gut microbiota, serum, and follicular fluid further demonstrated that the co-metabolites were phosphocholine and linoleic acid. Moreover, the expression of genes related to arachidonic acid metabolism in granulosa cells was significantly correlated with phosphocholine and linoleic acid. The results in granulosa cells showed that the levels of PLCB1 and COX2, participating in arachidonic acid metabolism, were increased in the DH group, which improved the concentrations of PGD2 and PGF2α in the follicular fluid. Finally, the expression levels of apoptosis-related proteins, cytokines, and steroidogenesis-related genes in granulosa cells and the concentrations of steroid hormones in follicular fluid were determinants of follicular development. According to our results, gut microbiota-related phosphocholine and linoleic acid participate in arachidonic acid metabolism in granulosa cells through the gut-follicle axis, which regulates follicular development. These findings hold promise for enhancing follicular development and optimizing oocyte quality in subfertile dairy cows.

The Most Influential Publications Regarding Hair Transplantation: A Bibliometric Review.

INTRODUCTION: This bibliometric review aims to assess the impact of significant publications within the field of hair transplantation. Citation counts will serve as a primary influence indicator. METHODS: An exhaustive search was conducted using Clarivate's Web of Science database, yielding 260 publications related to hair transplantation. These were evaluated and sorted based on citations, narrowing down to the 50 most highly cited works for analysis. Parameters including citation density, authorship, institutional affiliations, country of origin, year of publication, article topic, and the level of evidence for each publication were obtained. RESULTS: Analyzed publications were cited a total of 1341 times. Authorship analysis revealed that the most significant contributors regarding hair transplantation were Bernstein and Rassman. We also identified the leading institutions affiliated with these works, highlighting the primary academic and research centers driving the field. Geographical analysis exhibited the US' dominance in producing impactful publications. Most publications were also classified within Level IV and Level V according to the Oxford Levels of Evidence system. CONCLUSION: This review provides a comprehensive snapshot of the pivotal publications shaping hair transplantation. Our findings underscore significant contributions within this field and may assist researchers and clinicians in understanding the evolution and the current state of the hair transplantation literature. This bibliometric analysis can serve as a roadmap for those seeking to delve into this rapidly evolving field, facilitating the identification of research gaps and formulating future research directions. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Up-regulated mitochondrial biogenesis associated with GH/IGF axis in the ovaries of muskrats (Ondatra zibethicus).

Mitochondria play a critical role in follicular development and ovulation, at least in part through the actions of growth hormone (GH)/insulin-like growth factor-1 (IGF-1) on mitochondrial biogenesis. This study aimed to identify seasonal alterations in the GH/IGF-1 system and mitochondrial biogenesis in muskrat (Ondatra zibethicus) ovaries. We utilized the muskrat, a typical seasonal breeder, to clarify the potential impact of the GH/IGF-1 system on mitochondrial biogenesis across different breeding seasons using immunohistochemistry, gene expression and high-throughput sequencing. Alterations in follicular development existed in muskrat ovaries between the breeding season (BS) and non-breeding season (NBS), accompanied by a striking decrease in circulating and ovarian GH and IGF-1 concentrations. GH, GHR, IGF-1, IGF-1R, and mitochondrial biogenesis markers were localized in the ovarian cells of muskrats during both seasons. In contrast, Gh, Ghr, Igf-1, Igf-1r, Ppargc1a, Ppargc1b, Tfam, and Nrf1/2 mRNA levels were higher in BS. The relative levels of GH and IGF-1 in circulation and ovaries were positively associated with mitochondrial biogenesis markers. Additionally, RNA-seq analysis demonstrated that differentially expressed genes might be associated with insulin and PI3K/Akt signaling pathways, as well as mitochondrial function-related pathways. These findings suggest that the intra-ovarian GH/IGF-1 system, which is associated with seasonal changes in mitochondrial biogenesis, is activated in muskrat ovaries in BS.

Activation of circulating TFH17 cells associated with activated naive and double negative 2 B cell expansion, and disease activity in systemic lupus erythematosus patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. METHODS: Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. RESULTS: In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. CONCLUSION: SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.

Ectopic Follicular Variant of Papillary Thyroid Carcinoma in Anterior Neck Region with a Normal Thyroid Gland-A Rare Entity.

Ectopic thyroid tissue is defined as thyroid tissue that is present at a location other than its normal anatomical location. It can have any pathological condition that could impact the orthotopic thyroid gland. However, ectopic thyroid tissue seldom becomes malignant, and the occurrence of a follicular variant of papillary carcinoma in ectopic thyroid is much more unusual. We report a rare case of ectopic follicular variant of papillary carcinoma in a 73-year-old female with a normal orthotopic thyroid gland. Despite a few reports on ectopic papillary carcinoma thyroid (PTC) in submental, thyroglossal duct cysts, and bronchial cleft cysts with normal pathologic examinations of orthotopic thyroid, only one case of PTC in the anterior neck region without any neoplastic involvement of the orthotopic thyroid gland has been reported. Ectopic thyroid carcinoma should be taken into account in the differential diagnosis of a mass lesion in the front of the neck even in the presence of a normal thyroid gland which will aid in early diagnosis and treatment of such cases.

Predictive value of serum HIF-1α/HIF-2α and YKL-40 levels for vascular invasion and prognosis of follicular thyroid cancer.

OBJECTIVE: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). METHODS: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. RESULTS: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. CONCLUSION: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.

A Novel Treatment of Acne Vulgaris Using a 1927 nm Fractional Thulium Laser: A Case Series.

Background and Aims: Acne vulgaris remains one of the most common and problematic dermatological conditions. Recently, a fractional 1927 nm thulium laser has been developed with specific water absorption characteristics which may be of interest in the treatment of acne. Subjects and Methods: Nine consecutive Korean subjects, 6 females and 3 males, ages ranging from 13 to 33 yr, presented with a mixture of inflammatory and noninflammatory acne. Baseline clinical photography, image analysis and lesion counts were performed. A fractional 1927 nm thulium laser (FTL) delivered 6 treatment sessions in 5 subjects and 5 sessions in 4 subjects, 4 weeks between sessions. Pain during treatment was assessed. At 32 weeks after the last treatment session, an independent Investigator Global Assessment (IGA) performed lesion counts and graded the severity of the acne at baseline and the final assessment on a quintile scale. Data were analyzed statistically. Results: All 9 subjects completed the study with significant reductions in the inflammatory and noninflammatory lesions (P values 0.0012 and 0.0081, respectively) with overall lesion counts at the final assessment ranging from 60% to 97.1%, and acne grades in the IGA dropping by an average of 1.67 (range 1 to 3 grades). There was no significant difference in lesion counts or acne grades between the subjects who had 6 treatments and those who had 5 (P = 0.7695). Mild pain was reported during treatment, and no adverse events were reported by either the subjects or investigator. Conclusions: The FTL at the parameters used in the present study caused disruption to the upper portion of the affected follicles and sebaceous glands under an intact stratum corneum, thereby destroying or damaging the causative Cutibacterium acnes. The superficial controlled coagulation additionally induced follicular remodeling and tissue regeneration, potentially contributing to the noticeable results in inflammatory and noninflammatory acne lesions.

Activation and Regulation of Indirect Alloresponses in Transplanted Patients With Donor Specific Antibodies and Chronic Rejection.

Following transplantation, human CD4+T cells can respond to alloantigen using three distinct pathways. Direct and semi-direct responses are considered potent, but brief, so contribute mostly to acute rejection. Indirect responses are persistent and prolonged, involve B cells as critical antigen presenting cells, and are an absolute requirement for development of donor specific antibody, so more often mediate chronic rejection. Novel in vitro techniques have furthered our understanding by mimicking in vivo germinal centre processes, including B cell antigen presentation to CD4+ T cells and effector cytokine responses following challenge with donor specific peptides. In this review we outline recent data detailing the contribution of CD4+ T follicular helper cells and antigen presenting B cells to donor specific antibody formation and antibody mediated rejection. Furthermore, multi-parametric flow cytometry analyses have revealed specific endogenous regulatory T and B subsets each capable of suppressing distinct aspects of the indirect response, including CD4+ T cell cytokine production, B cell maturation into plasmablasts and antibody production, and germinal centre maturation. These data underpin novel opportunities to control these aberrant processes either by targeting molecules critical to indirect alloresponses or potentiating suppression via exogenous regulatory cell therapy.

Report of successful treatment of follicular occlusion triad with adalimumab and research progress on biologic therapy for follicular occlusion triad.

Purpose: This article aims to present a case report of a patient with Follicular occlusion triad (FOT) who achieved successful disease control with adalimumab combined with isotretinoin and provide a comprehensive review of the current research progress on biologic therapies for FOT.Methods: We report a case of a 22-year-old female patient diagnosed with FOT, who was treated with adalimumab combined with isotretinoin after failing to respond to conventional therapies. A systematic literature review was conducted to summarize the current research progress on biologic therapies for FOT, including TNF-α inhibitors, IL-17 inhibitors, IL-12/IL-23 inhibitors, IL-23 inhibitors, IL-1 inhibitors, and other novel biologic agents.Results: The patient achieved significant improvement in skin lesions, pain, and quality of life after three months of treatment with adalimumab combined with isotretinoin, without experiencing severe adverse reactions. The literature review revealed that adalimumab and secukinumab are the two FDA-approved biologics for FOT, while others, such as bimekizumab, infliximab, anakinra, and bermekimab, have shown promise in clinical studies.Conclusions: Biologic therapies have revolutionized FOT management, providing effective options for patients unresponsive to conventional treatments. As our understanding of FOT pathogenesis and the mechanisms of action of biologics grows, further advancements in biologic therapies for FOT are expected.

Impact of positive CD4 cells on event-free survival in follicular lymphoma patients.

OBJECTIVE: Previous results about prognostic value of CD4+ T cells in follicular lymphoma (FL) remain controversial. METHODS: Immunohistochemistry was used to examine expression of positive CD4 cells in 103 patients with FL 1-3A. Early failure was described as failing to achieve event-free survival (EFS) at 12 or 24 months. RESULTS: There were 49 (47.6%) male and 54 (52.4%) females, with a median age of 54 years. Compared to patients with <20% of positive CD4 cells, patients with ≥20% of positive CD4 cells exhibited a significant lower risk of early failure (2-year EFS rate: 56.7% vs 73.5%, p = 0.047). When patients were stratified based on positive CD4 cell combined with FLIPI, the median EFS (p = 0.002) and median OS (p = 0.007) were significantly different. CONCLUSIONS: This study demonstrated that higher expression of positive CD4 cells predicts lower risk of early failure in follicular lymphoma, and combination analysis of CD4 and FLIPI could better predict disease relapse and survival outcome.

Concurrent Oral Squamous Cell Carcinoma and Incidental Papillary Thyroid Carcinoma Metastasis in Cervical Lymph Nodes: A Case Report.

Oral squamous cell carcinoma (OSCC) is the most common of all head and neck cancers accounting for 90% of all oral malignancies. It is commonly associated with the use of tobacco smoking or quid form. The incidence of oral carcinoma is higher in males than females with a ratio of 1.4:1, though females commonly adopt tobacco quid chewing habit. OSCC metastasis to cervical lymph node at the rate of 20-42.6% according to studies reported so far. Papillary thyroid carcinoma (PTC) occurs with a higher incidence in females than males with metastasis into cervical lymph nodes though the primary lesion frequently goes undetected. Concurrent metastasis of OSCC and PTC to the cervical lymph node during neck dissection has been reported rarely in the literature. This case report presents a 48-year-old female with lymph node metastasis of carcinoma of the right mandibular posterior alveolar region concurrently with metastasis of PTC (with primary lesion clinically undetected) encountered during cervical lymph node examination.

Positive Effect of 25-Hydroxyvitamin D (25(OH)D) Levels in Follicular Fluid on Embryonic Developmental Potential in Diminished Ovarian Reserve (DOR) Patients Undergoing Microstimulation.

OBJECTIVE: This study aimed to explore the effect of 25-hydroxyvitamin D (25(OH)D) levels in follicular fluid (FF) on the embryo outcome with diminished ovarian reserve (DOR) patients undergoing in vitro fertilization (IVF) by microstimulation protocol. METHODS: A prospective cohort study of 79 patients with DOR who underwent IVF using the microstimulation protocol was conducted. Based on the level of 25(OH)D in follicular fluid (25(OH)D-FF), the patients were divided into a high-value group (25(OH)D-FF>11.1, n = 50) and a low-value group (25(OH)D-FF>11.1, n = 29). Correlation analysis was conducted between the level of 25(OH)D-FF and the rate of high-quality embryos on day 3 (D3). Logistic regression analysis of factors affecting the presence or absence of D3-available embryos in patients with DOR was conducted. RESULTS: The number of oocytes retrieved, mature oocytes (MII), normal fertilization rate, number of available embryos on D3, and high-quality embryo rate were lower in the low-value group than in the high-value group (p = 0.000, p = 0.000, p = 0.009, p = 0.000, p = 0.001). The clinical pregnancy rate of frozen embryo transfer (FET) between the two groups was no statistically significant difference (p > 0.05); correlation analysis between the 25(OH)D-FF level and the rate of high-quality embryos was performed using Spearman's rank-sum test, and there was a positive correlation (R = 0.271, P<0.01). Logistic analysis showed that 25(OH)D-FF level was a protective factor for embryonic outcome (odds ratio (OR) > 1, P<0.01). CONCLUSION: The 25(OH)D level in FF has a positive effect on embryonic outcomes in DOR patients with IVF using the microstimulation protocol. Vitamin D (VD) supplementation can be used to increase the number of available embryos and improve the quality of embryos for patients with DOR who are undergoing microstimulation of IVF.

A Case of Follicular Atresia Triad Combined with Necrotising Fasciitis and Squamous Carcinoma of the Lower Limbs.

Follicular atresia triad, also known as paradoxical acne (FOT), is a rare and serious clinical syndrome in dermatology, mainly manifested by coalescing acne, purulent perifolliculitis of the head, and suppurative sweating inflammation, and FOT combined with necrotising fasciitis of the lower limbs and squamous cell carcinoma is rare both at home and abroad. In this article, we share the clinical data and treatment of a patient with follicular atresia triad and necrotising fasciitis and squamous cell carcinoma of the left lower limb for your reference.

Associations between neonicotinoid insecticide levels in follicular fluid and serum and reproductive outcomes among women undergoing assisted reproductive technology: An observational study.

Neonicotinoid insecticides (NEOs) are a widely used type of insecticide found globally, leading to broad human exposure. However, there is limited research on how internal exposure levels of NEOs and their metabolites impact in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. A study was conducted at the Sixth Affiliated Hospital of Sun Yat-sen University between 2017 and 2020 involving 436 women undergoing IVF/ICSI treatment. Data on demographics and clinical history were collected from medical records. The concentrations of 11 NEOs and 4 NEO metabolites in follicular fluid and serum were measured using a salting-out assisted liquid-liquid extraction method and liquid chromatography-tandem mass spectrometry. Our findings indicated that NEOs were prevalent in women with infertility. One NEO metabolite, N-dm-ACE, was detected in all samples with median concentrations of 0.221 ng/mL in follicular fluid and 0.228 ng/mL in serum. The study showed a decrease in the number of retrieved oocytes, mature oocytes, 2 PN zygotes, and high-quality embryos as the number of exposed NEOs in follicular fluid increased. Women in the highest tertile of N-dm-ACE exposure had fewer mature oocytes, 2 PN zygotes, and lower oocyte maturity rates compared to those in the lowest tertile. The findings suggest that exposure to NEOs may negatively impact reproductive outcomes in IVF/ICSI pregnancies, particularly affecting oocyte retrieval and embryo quality. This study highlights the potential adverse effects of environmental NEO exposure on IVF/ICSI outcomes, emphasizing the importance of considering such exposures in preconception care.

Amelioration of immunoglobulin A vasculitis by suppression of the pathological expansion of T follicular helper 17 cells.

The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.

Regulation of the IgE response by T follicular regulatory cells.

Allergen-specific IgE is a major mediator of allergic responses and contributes greatly to allergic disease in the human population. Therapies that inhibit the production of IgE would be useful for lessening the burden of allergic disease. A great deal of research has focused on how IgE responses are regulated, and several factors that promote the production of allergic IgE have been characterized. T follicular helper (TFH) cells expressing IL-4 are required for the development of IgE expressing B cells in the germinal center (GC). Ig somatic hypermutation and B cell selection in the GC leads to the development of high affinity allergen-specific IgE that promotes anaphylaxis, a severe form of allergic response. T follicular regulatory (TFR) cells are also found in the GC response and act with TFH cells in the selection of high affinity IgE + B cells. This review examines the current literature on IgE responses and TFR cells. In mouse studies, TFR cells have a suppressive role on IgE responses in allergic airway disease, however TFR cells also play a helper role in the IgE response in food allergy. In human studies, TFR cells correlate with a decreased allergic response but evidence for a direct suppressive role of TFR cells on IgE in vivo is lacking. TFR cells may represent a new target for allergy therapies, but caution must be exercised to promote the suppressor activity of TFR cells and not the helper activity of TFR cells on IgE responses.

Efficacy and safety of microwave ablation for treatment of follicular thyroid neoplasms: a preliminary study.

OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.