Association Between Proton Pump Inhibitor Use and Overactive Bladder Risk in Adults: A Cross-Sectional Study.

OBJECTIVES: To investigate the association between the use of Proton Pump Inhibitors (PPIs) and Overactive Bladder (OAB) in adults. METHODS: This study adopts a cross-sectional approach to scrutinize data derived from the National Health and Nutrition Examination Survey (NHANES), spanning from 2007 to 2018. It employs multivariable logistic regression along with restricted cubic splines (RCS) to investigate the relationship between the use of PPI and the incidence of OAB. Additionally, through interaction and stratification analyses, the study delves into how specific factors may influence this correlation. RESULTS: A total of 24,458 adults participated in this study. Individuals using PPIs exhibited higher rates of nocturia, urge incontinence, and OAB compared to non-users. After full adjustment, PPI users had a significantly increased risk of developing OAB (OR = 1.36, 95%CI: 1.17-1.60). Moreover, with each year of continued PPI usage, the frequency of OAB symptoms escalated by 3% (p=0.01). Further examinations within various subgroups maintained a uniform direction in these effect estimates. CONCLUSIONS: The findings of this research highlight a noteworthy positive link between the use of PPIs and the emergence of OAB among adults. Moreover, it was observed that an extended period of using PPIs correlates with a heightened likelihood of encountering OAB.

Integrating multiregulatory analysis reveals the negative regulatory function of miR482a in the response of poplar to canker pathogen infection.

Canker disease caused by the bacterium Lonsdalea populi is one of the most destructive diseases affecting poplar stems. However, the detailed stress response mechanisms of poplar have not been widely characterized. To explore the diverse regulatory RNA landscape and the function of key regulators in poplar subjected to L. populi stress, we integrated time-course experiment with mock-inoculation (CK) and inoculation (IN) with L. populi at the first, third, and sixth day (IN1, IN3, IN6) on Populus × euramericana cv. '74/76' (107), small RNA-seq, whole transcriptome-wide analysis, degradome analysis and transgenic experiments. A total of 98 differentially expressed (DE) miRNA, 17 974 DEmRNA, and 807 DElncRNA were identified in poplar infected by L. populi, presenting dynamic changes over the infection course. Regulatory networks among RNAs were further constructed. Notably, a network centered on ptc-miR482a in CK-vs-IN3 contained most DEGs. We show that miR482a and miR1448 are located in one transcript as a polycistron. Overexpression of pre-miR482a-miR1448 (OX482-1448) and pre-miR482a (OX482) increased poplar susceptibility to canker pathogen with reduced accumulation of reactive oxygen species, while the suppression of miR482a (STTM482) conferred poplar disease resistance. PHA7 was validated as the target of miR482a with degradome sequencing and tobacco transient co-transformation, its expression being downregulated in OX482-1448 and OX482 lines. Additionally, a series of phasiRNAs were triggered by miR482a targeting PHA7, forming regulatory cascades with more RLP, NBS-LRR, and PK genes, further verifying the defense function of miR482a. These findings provide insights for understanding the roles of ncRNAs and regulatory networks involved in poplar immunity.

Type 2 diabetes mellitus modifies and mediates the association between the visceral adiposity index and depression: A cross-sectional study using NHANES 2005-2018 data.

BACKGROUND: The objective of this investigation was to explore the correlation between the visceral adiposity index (VAI) and depression, and to analyze how type 2 diabetes mellitus (T2DM) may influence this relationship. METHODS: This study included data of 12,378 participants sourced from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Utilizing multivariate logistic regression and restricted cubic spline (RCS) regression, we examined the correlation between VAI and depression. Additionally, we investigated the interactive and mediating effects of T2DM on the association between VAI and depression. RESULTS: Controlling for all potential confounders, the Ln logarithmic transformation of VAI showed a significant positive correlation with depression [odds ratio (OR) = 1.16, 95 % confidence interval (CI): 1.01-1.35, P = 0.041]. T2DM exhibited a notable interaction effect on the relationship connecting lnVAI and depression (P for interaction = 0.013). Specifically, the T2DM group exhibited a notable positive correlation between lnVAI and depression (OR = 1.46, 95 % CI: 1.17-1.82, P < 0.001), whereas such correlation didn't reach statistical significance within the non-T2DM group. The RCS model revealed a J-shaped nonlinear link between lnVAI and depression, with an inflection point value of 0.052. Mediation analysis indicated that diabetes accounted for 8.0 % of the correlation between lnVAI and depression. Furthermore, sensitivity analysis confirmed the consistency of these findings. CONCLUSIONS: A J-shaped nonlinear dose-response relationship was observed between lnVAI and depression among American adults, with a threshold of 0.052. T2DM not only served as a mediator between the two variables but also modified their association.

Nanobiotechnology-mediated regulation of reactive oxygen species homeostasis under heat and drought stress in plants.

Global warming causes heat and drought stress in plants, which affects crop production. In addition to osmotic stress and protein inactivation, reactive oxygen species (ROS) overaccumulation under heat and drought stress is a secondary stress that further impairs plant performance. Chloroplasts, mitochondria, peroxisomes, and apoplasts are the main ROS generation sites in heat- and drought-stressed plants. In this review, we summarize ROS generation and scavenging in heat- and drought-stressed plants and highlight the potential applications of plant nanobiotechnology for enhancing plant tolerance to these stresses.

Birthweight influences liver structure, function and disease risk: Evidence of a causal association.

AIM: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators. RESULTS: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%). CONCLUSIONS: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.

Golgi apparatus regulated pyroptosis through the miR-32-5p/Golga7/NLRP3 axis in chicken splenic lymphocytes exposure to ammonia.

Ammonia, a common toxic gas, posed a hazard to both human and chickens. The Golgi apparatus, an essential organelle, helped maintain the internal environment of the organism and supported the protein foundation for the endoplasmic reticulum to be involved in pyroptosis. Thus, the Golgi apparatus has garnered significant attention. The purpose of our research was to explore the mechanisms of Golgin A7 (Golga7) involved in pyroptosis after chicken exposure to ammonia. To reach our goal, we first created an in vitro ammonia model to study the effect of ammonia on chicken splenic lymphocyte pyroptosis. Then, leveraging this model, we established Golga7 and miR-32-5p knockdown and overexpression models to investigate their roles in ammonia-induced pyroptosis. We found the ultrastructural changes in the nucleus, Golgi apparatus, and mitochondria of chicken splenic lymphocytes exposure to ammonia. The damage of mitochondria increased the level of Reactive Oxygen Species (ROS), which caused the down-regulation of miR-32-5p. The miR-32-5p inhibitor increased the expression of Golga7 and pyroptosis-related genes (NOD-like receptor protein 3 (NLRP3), Cysteine aspartase-1 (Caspase-1), Golgin A3 (Golga3), Nuclear Factor-kappa B (NF-κB), and Tumor Necrosis Factor-alpha (TNF-α)), which induced the pyroptosis, but when miR-32-5p mimic/si-Golga7 (Golga7 inhibitor) was utilized, these effects were reduced. Our research demonstrated that miR-32-5p/Golga7 regulated NLRP3 involving in the pyroptosis of chicken splenic cells exposed to ammonia. Our study provided a valuable foundation for the prevention and treatment chickens ammonia poisoning in the livestock production.

Cross-domain additive learning of new knowledge rather than replacement.

In medical clinical scenarios for reasons such as patient privacy, information protection and data migration, when domain adaptation is needed for real scenarios, the source-domain data is often inaccessible and only the pre-trained source model on the source-domain is available. Existing solutions for this type of problem tend to forget the rich task experience previously learned on the source domain after adapting, which means that the model simply overfits the target-domain data when adapting and does not learn robust features that facilitate real task decisions. We address this problem by exploring the particular application of source-free domain adaptation in medical image segmentation and propose a two-stage additive source-free adaptation framework. We generalize the domain-invariant features by constraining the core pathological structure and semantic consistency between different perspectives. And we reduce the segmentation generated by locating and filtering elements that may have errors through Monte-Carlo uncertainty estimation. We conduct comparison experiments with some other methods on a cross-device polyp segmentation and a cross-modal brain tumor segmentation dataset, the results in both the target and source domains verify that the proposed method can effectively solve the domain offset problem and the model retains its dominance on the source domain after learning new knowledge of the target domain.This work provides valuable exploration for achieving additive learning on the target and source domains in the absence of source data and offers new ideas and methods for adaptation research in the field of medical image segmentation.

PagTPS1 and PagTPS10, the trehalose-6-phosphate synthase genes, increase trehalose content and enhance drought tolerance.

Trehalose-6-phosphate synthase (TPS) genes play an active role in the trehalose metabolism pathway that regulates the responses of plants to diverse stresses. However, the functional identification, comparison, and conservatism of TPS genes in the responses of woody plants, especially poplars, to drought stress remain unclear. Here, the trehalose content of 84K (Populus alba × P. glandulosa) poplars was down-regulated and PagTPS and PagTPP genes had diverse response patterns under drought stress. Physicochemical properties, expression patterns, and functions of PagTPS1 and PagTPS10, two class I members of TPS gene family, were identified and compared. Transgenic 84K poplars overexpressing PagTPS1 and PagTPS10 had significantly higher trehalose content with approximately 138% and 123%, respectively, and stronger drought tolerance compared to WT. PagTPS1 and PagTPS10 promoted the expression of TPPA genes and drought-responsive genes. Accordingly, poplars inhibiting PagTPS1 and PagTPS10 expression via RNA interference had lower trehalose content and drought tolerance. Simultaneously, overexpressing PagTPS1 and PagTPS10 improved the trehalose content and drought tolerance of Arabidopsis. Overall, we proposed a model of the effects of PagTPS1 and PagTPS10 as conservative regulators on the responses of plants to drought, which would provide new insights into the functional explorations of TPS genes in plants.

Vitamin D content and prevalence of vitamin D deficiency in patients with epilepsy: a systematic review and meta-analysis.

Introduction: The prevalence of vitamin D deficiency and vitamin D levels in patients with epilepsy (PWE) were systematically evaluated, and the differences between subgroups were analyzed. Method: We identified all articles investigating the prevalence of vitamin D deficiency in patients with epilepsy from the database established in March 2024 from PubMed, Web of Science, and Embase. We divided them into anti-seizure medication (ASM) interventions and non-ASM interventions according to whether or not someone used ASM. Results: A total of 68 articles were included. The prevalence of newly diagnosed epilepsy was 50.2% (95% CI: 38.7-61.7%), and the prevalence after ASM intervention was 47.9% (95% CI: 40-55.9%), including 7,070 patients with epilepsy. Subgroup and meta-regression analyses were performed according to the diagnostic criteria, economic development level, region, age, ASM treatment, and other factors. The results showed that the differences were not significant. In addition, the vitamin D content of epilepsy patients (18.719 ng/mL) was lower than that of healthy people (20.295 ng/mL). Conclusion: The prevalence of vitamin D deficiency in patients with epilepsy is very high. Still, the related factors have little effect on the high prevalence of vitamin D in epilepsy, and ASM intervention can reduce the vitamin D content in patients with epilepsy. Therefore, it is emphasized that monitoring vitamin D levels is part of the routine management of patients with epilepsy. Systematic review registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). (registration number CRD42023493896). https://www.crd.york.ac.uk/PROSPERO/ # myprospero.

Facile One-Pot Preparation of Polypyrrole-Incorporated Conductive Hydrogels for Human Motion Sensing.

Conductive hydrogels have been widely used in soft robotics, as well as skin-attached and implantable bioelectronic devices. Among the candidates of conductive fillers, conductive polymers have become popular due to their intrinsic conductivity, high biocompatibility, and mechanical flexibility. However, it is still a challenge to construct conductive polymer-incorporated hydrogels with a good performance using a facile method. Herein, we present a simple method for the one-pot preparation of conductive polymer-incorporated hydrogels involving rapid photocuring of the hydrogel template followed by slow in situ polymerization of pyrrole. Due to the use of a milder oxidant, hydrogen peroxide, for polypyrrole synthesis, the photocuring of the hydrogel template and the growing of polypyrrole proceeded in an orderly manner, making it possible to prepare conductive polymer-incorporated hydrogels in one pot. The preparation process is facile and extensible. Moreover, the obtained hydrogels exhibit a series of properties suitable for biomedical strain sensors, including good conductivity (2.49 mS/cm), high stretchability (>200%), and a low Young's modulus (~30 kPa) that is compatible with human skin.

A novel synthesis method of medium- and long-chain triglyceride lipids from rubber seed oil catalyzed by enzymatic interesterification and its metabolism mechanism.

Medium- and long-chain triglyceride (MLCT) is a striking structural lipid for the supply of energy and essential fatty free acids (FFAs) in the food field. This study aimed to prepare MLCT by enzymatic interesterification of rubber seed oil (RSO) and medium-chain triglyceride (MCT). Fortunately, the conversion of synthesized MLCT could reach 75.4% by the catalysis of Novozym 40086 (7 wt% to MCT) at a temperature of 40 °C with the substrate mole ratio of 1 : 0.7 (RSO : MCT). The as-synthesized MLCT contained unsaturated fatty acid (USFA, 50.13%) at the sn-2 position and exhibited superior performance on the acid value, peroxide value and iodine value in contrast to grade III soybean oil. Moreover, it exhibited the simultaneous release of LCFAs and MCFAs, extremely facilitating the reduction of body weight gain and control of the level of lipids in the blood. Finally, the preferred hepatic metabolism process of the obtained MLCT was proven to be the main cause of the reduced body weight and improved lipid levels by the in vivo deposition experiments. Therefore, our study suggested that the outstanding performance of the MLCT synthesized by RSO in foods as functional lipids.

Development of Axially Chiral Pyridylidene Amine Ligands and their Application in Pd-Catalyzed Enantioselective Allylic Substitution.

A series of novel axially chiral pyridylidene amine (PYE) ligands has been developed, and their catalytic capability has been demonstrated in various highly efficient and enantioselective Pd-catalyzed asymmetric allylic substitutions. A density-functional theory (DFT) study explains the preferential enantiocontrol in the key transition states of the axially chiral PYE ligand-promoted Pd-catalyzed allylic alkylation.

New perspective for pathomechanism and clinical applications of animal toxins: Programmed cell death.

Various animal toxins pose a significant threat to human safety, necessitating urgent attention to their treatment and research. The clinical potential of programmed cell death (PCD) is widely regarded as a target for envenomation, given its crucial role in regulating physiological and pathophysiological processes. Current research on animal toxins examines their specific components in pathomechanisms and injuries, as well as their clinical applications. This review explores the relationship between various toxins and several types of PCD, such as apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, to provide a reference for future understanding of the pathophysiology of toxins and the development of their potential clinical value.

Altered sleep onset transition in depression: Evidence from EEG activity and EEG functional connectivity analyses.

OBJECTIVE: Sleep disorders constitute a principal diagnostic criterion for depression, potentially reflecting the abnormal persistence of brain activity during the sleep onset (SO) transition. Here, we sought to explore the differences in the dynamic changes in the EEG activity and the EEG functional connectivity (FC) during the SO transition in depressed patients. METHODS: Overnight polysomnography recordings were obtained from thirty-two depressed patients and thirty-three healthy controls. The multiscale permutation entropy (MSPE) and EEG relative power were extracted to characterize EEG activity, and weighted phase lag index (WPLI) was calculated to characterize EEG FC. RESULTS: The intergroup differences in EEG activity of relative power and MSPE were reversed near SO, which attributed to slower rates of change among depressed patients. Regarding the characteristics of the EEG FC network, depressed patients exhibited significantly higher inter-hemispheric and interregional WPLI values in both delta and alpha bands throughout the SO transition, concomitant with different dynamic properties in the delta band FC. During the process after SO, patients exhibited increased inter-hemispheric long-range links, whereas controls showed more intra-hemispheric ones. Finally, we found significant correlations in the dynamic changes between different EEG measures. CONCLUSIONS: Our research revealed that the abnormal changes during the SO transition in depressed patients were manifested in both homeostatic and dynamic aspects, which were reflected in EEG FC and EEG activity, respectively. SIGNIFICANCE: These findings may elucidate the mechanism underlying sleep disorders in depression from the perspective of neural activity.

Various effects of feeding level on ammonia tolerance in Carassius auratus under different ammonia exposure stress and the underlying mechanisms.

Elevated ammonia levels in aquaculture systems could reduce fish growth and survival rates and produce a range of physiological problems. Ammonia toxicity in aquatic environments was regulated by various factors. Feeding was usually reported to help in the detoxification of fish, thereby increasing their capacity to tolerate ammonia nitrogen. However, the impact of different feeding amounts on fish in relation to ammonia exposure stress remains to be determined. To determine how feeding levels affected fish's responses to different ammonia nitrogen concentrations, two acute toxicity experiments were conducted with Carassius auratus gibelio, the major strain of gibel carp in aquaculture systems in China. In Test I, fed Carassius auratus gibelio (3 % body weight) showed a higher survival rate under a specific ammonia exposure stress. 96-h LC50 of NH3-N to 3 %F gibel carp was 1.1 times greater than that for NF (no feeding). In Test II, all fed groups (2 %F and 4 %F) under low and high ammonia stress exhibited improved ammonia detoxification, evidenced by higher liver GSase, GDH, and glutamine concentrations compared with the NF treatment. Muscle glycogen levels in feeding treatments were higher than those in NF, indicating that fed fish have more energy for ammonia detoxification. While compared with low ammonia treatment (2.70 mg L-1 TAN; NH3 0.06 mg L-1), fish exposed to high ammonia levels (26.03 mg L-1 TAN; NH3 0.57 mg L-1) demonstrated a decrease in food consumption, severe histopathological alterations in their liver, gill, and kidney, and decreased GSase, GDH, and glutamine production in the liver and brain. The results partly supported our hypothesis and suggested that increasing feeding enhances gibel carp's tolerance to ammonia nitrogen. The highest detoxification metabolism was observed under low ammonia stress. While excessive ammonia exposure could inhibit feeding and damage the detoxification organs of fish, and thus reduce the detoxification metabolism of gibel carp.

Elucidating the interaction of rhizosphere microorganisms and environmental factors influencing the quality of Polygonatum kingianum Coll. et Hemsl.

Polygonatum kingianum Collett & Hemsl., is one of the most important traditional Chinese medicines in China. The purpose of this study is to investigate the relationship between herb quality and microbial-soil variables, while also examining the composition and structure of the rhizosphere microbial community in Polygonatum kingianum, the ultimate goal is to provide a scientific approach to enhancing the quality of P. kingianum. Illumina NovaSeq technology unlocks comprehensive genetic variation and biological functionality through high-throughput sequencing. And in this study it was used to analyze the rhizosphere microbial communities in the soils of five P. kingianum planting areas. Conventional techniques were used to measure the organic elements, pH, and organic matter content. The active ingredient content of P. kingianum was identified by High Performance Liquid Chromatography (HPLC) and Colorimetry. A total of 12,715 bacterial and 5487 fungal Operational Taxonomic Units (OTU) were obtained and taxonomically categorized into 81 and 7 different phyla. Proteobacteria, Bacteroidetes, and Acidobacteriae were the dominant bacterial phyla Ascomycota and Basidiomycota were the dominat fungal phyla. The key predictors for bacterial community structure included hydrolysable nitrogen and available potassium, while for altering fungal community structure, soil organic carbon content (OCC), total nitrogen content (TNC), and total potassium content (TPOC) were the main influencing factors. Bryobacter and Candidatus Solibacter may indirectly increase the polysaccharide content of P. kingianum, and can be developed as potential Plant Growth Promoting Rhizobacteria (PGPR). This study has confirmed the differences in the soil and microorganisms of different origins of P. kingianum, and their close association with its active ingredients. And it also broadens the idea of studying the link between plants and microorganisms.

Effects of a phytobiotic-based additive on the growth, hepatopancreas health, intestinal microbiota, and Vibrio parahaemolyticus resistance of Pacific white shrimp, Litopenaeus vannamei.

Vibrio genus is a common pathogen in aquaculture and causes acute hepatopancreatic necrosis disease (AHPND) and massive mortality of shrimp. Many studies have suggested that a single functional ingredient such as plant extract or organic acid can reduce the dependence on antibiotics and promote the growth and immunity of aquatic animals. In this study, we evaluated the effects of a phytobiotic-based compound additive (Sanacore® GM, SNGM), which had a successful trajectory of commercial application in fish farming. However, its effects on the hepatopancreas health and intestinal microbiota of shrimp after Vibrio challenge have not been well evaluated. In the present study, Pacific white shrimp were fed diets with or without supplementation of SNGM, and the SNGM grades were 0-g/kg (CON), 3-g/kg (SNGM3), and 5-g/kg (SNGM5) diets. The feed trial lasted 60 days, after which a Vibrio parahaemolyticus challenge was performed. The results showed that compared to the CON group, both the SNGM3 and SNGM5 groups had a significantly higher weight gain and a lower feed conversion ratio as well as higher survival after Vibrio parahaemolyticus challenge. In the growth trial, the SNGM3 group had a significantly increased total protein, albumin concentration, and acid phosphatase activity in hemolymph compared to the CON group. In the challenge experiment, the SNGM3 and SNGM5 groups had increased albumin and glucose contents as well as the activities of phenoloxidase, lysozyme, alkaline phosphatase, and superoxide dismutase in hemolymph. Both the SNGM3 and SNGM5 groups had improved morphology of the hepatopancreas and intestine. The SNGM5 group had alleviated gut microbiota dysbiosis induced by Vibrio infection by increasing the potential probiotic bacterium abundance (Shewanella) and decreasing the potential pathogenic bacteria abundance (Vibrio, Photobacteriuma, Pseudoalteromonas, and Candidatus_Bacilloplasma). In conclusion, the dietary phytobiotic-based additive at 3-g/kg level increased the growth and Vibrio parahaemolyticus resistance of Pacific white shrimp by promoting immune-related enzyme activities and improving the morphological structure of the hepatopancreas and intestine and the intestinal microbiota composition.

Endocrine cancer trends 1990-2021: global disparities and health inequalities.

This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% confidence intervals (CI). Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = -0.83, 95% CI: -0.92 to -0.74), BC (AAPC = -0.48, 95% CI: -0.56 to -0.39), and TC (AAPC = -0.23, 95% CI: -0.29 to -0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. higher social development index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.

Genetic background and intraoperative haemodynamic instability in patients with pheochromocytoma and paraganglioma: a multicenter retrospective study.

BACKGROUND: Perioperative management to maintain intraoperative haemodynamic stability is crucial during surgical treatment of pheochromocytomas and paragangliomas (PPGLs). Although approximately 70% of PPGLs carry pathogenic variants (PVs) in susceptibility genes, whether intraoperative haemodynamic instability (IHI) is associated with genetic background remains unclear. This study aimed to analyse IHI in patients with PPGL due to PVs in different genes. MATERIALS AND METHODS: This retrospective study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information including sex, age, catecholamine-associated signs and symptoms (CAS), tumour location and size, biochemistry, and perioperative characteristics were collected. Genetic mutations were investigated using next-generation sequencing. RESULTS: Among the 671 patients included in the analysis, 61.8% (415/671) had IHI. IHI was significantly associated with genetic background in patients with PPGL. Most (80.9%, 89/110) patients with PPGL due to PVs in HRAS suffered IHI. In contrast, only half (31/62) of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, compared to those with negative genetic testing results, patients with PPGL due to PVs in HRAS (OR 3.82, 95% CI 2.187-6.679, P<0.001), the other cluster 2 genes (OR 1.95, 95% CI 1.287-2. 569, P< 0.05), and cluster 1 genes other than VHL (OR 2.35, 95% CI 1.338-4.111, P<0.05) were independent risk factors for IHI, while PVs in VHL was not independent risk factor (OR 1.09, 95% CI 0.605-1.953, P>=0.05). In addition, age at diagnosis of primary tumour, presenting of CAS, and tumour size were identified as independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS. CONCLUSION: IHI is associated with the genetic background in patients with PPGL. The perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.