Characterization of the potential allergenicity of enzymatically hydrolyzed casein in Balb/c mouse model.

Bovine casein is a major allergen present in cow milk to induce anaphylaxis. In this study, the potential allergenicity of enzymatically hydrolyzed casein (HC) was evaluated based on in vitro and in vivo. The results showed that Alcalase and Protamex treatment (AT, PT) reduced the potential allergenicity of CN, with the greatest reductions of 68.25% and 50.75%, respectively. In addition, in vivo results showed that HC effectively alleviated allergic response symptoms of Balb/c mice; a significant tendency toward decreased serum IgG1 and mast cell tryptase levels was observed, accompanied by a decrease of Th2-associated IL-4, IL-5, and IL-13 and an increase of IFN-γ levels in spleen. Moreover, the inflammation of the lung, jejunum, and ileum was remarkably ameliorated. The findings indicated that HC induced a shift toward Th1 response and maintained the Th1/Th2 immune balance. Importantly, our results provide the basis for the production of hypoallergenic dairy products.

Maternal dietary cholesterol and egg intake during pregnancy and large-for-gestational-age infants: a prospective cohort study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversial over whether pregnant women should limit their cholesterol intake. OBJECTIVES: To investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4,146 mother-child pairs were included based on the Jiangsu Birth Cohort (JBC) study. Maternal dietary information was assessed with a semi-quantitative food-frequency questionnaire (FFQ). Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations (GEE) were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase of birth weight z-score, with per SD increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 (95% CI: 0.07, 0.25) and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters were positively linked to LGA, with adjusted relative risk (aRR) of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared to mothers consuming ≤7 eggs/week in the third trimester, aRR for having LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/week and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/week (p for trend=0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/week during pregnancy displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Prevalence data for total corneal astigmatism in cataract patients.

PURPOSE: To report the prevalence data for total corneal astigmatism (TCA) in cataract patients. METHODS: The authors retrospectively collected and analyzed the preoperative biometric data of the patients who underwent cataract surgery in the Department of Ophthalmology, Peking University Third Hospital, from January 2019 to May 2023. RESULTS: The mean age of the 10817 patients was 71 ± 10 years; the male/female ratio was 4653/6164. The mean TCA obtained by the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany), the Abulafia-Koch (AK) formula, and the Barrett toric calculator was 1.11 ± 0.81 diopter (D), 1.13 ± 0.75 D, and 1.12 ± 0.74 D respectively, which was significantly greater than the mean standard keratometric (K) astigmatism (0.99 ± 0.75 D) obtained by IOLMaster 700. Against-the-rule (ATR) astigmatism was dominant in all the TCA measurements, and its proportion increased with age. TCA measurements by different methods exhibit high variability, with a total of 1574 (8.9%) data sets from 1016 (9.4%) patients showing a difference larger than 0.5 D in at least one pair of TCA measurements. CONCLUSION: The use of TCA rather than K astigmatism significantly influenced the choice of intraocular lenses (IOLs) as more patients would be candidates for toric IOLs. It was essential to carefully compare and select TCA obtained with multiple methods for optimal postoperative visual quality.

Relationship between stigma and infertility-related stress among couples undergoing AID: The mediating role of communication patterns.

Infertility can be stressful for infertile couples. This study aims to examine the intra-dyadic associations between stigma, communication patterns, and infertility-related stress in couples undergoing artificial insemination by donor semen (AID). This cross-sectional study was conducted from January to April 2021. Two hundred and three couples undergoing AID were recruited from a reproductive centre in China. All of the couples completed a two-item stigma questionnaire, Communication Pattern Questionnaire, and Fertility Problem Inventory. The actor-partner interdependence mediation analysis was performed using AMOS 23.0. The analysis demonstrated significant actor-actor effects for couples undergoing AID. More specifically, higher levels of stigma among wives and husbands were associated with more negative communication patterns, thereby increasing their own infertility-related stress. Simultaneously, there was a significant partner-actor effect among infertile wives, demonstrating that the husband's stigma can affect his wife's infertility-related stress by influencing her communication patterns. Couples undergoing AID experience increased infertility-related stress when they have high levels of stigma and negative communication patterns, and husbands' stigma is correlated to wives' communication patterns. Therefore, dyadic interventions aiming to improving stigma and enhancing positive communication may be conducive to reducing infertility-related stress.

Prevalence of cigarette use and addiction among Chinese females by age and province: Findings from nationwide China Health Literacy Survey during 2018-19.

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.

Konjac Oligosaccharides Alleviated Ovariectomy-Induced Bone Loss through Gut Microbiota Modulation and Treg/Th17 Regulation.

Oligosaccharides from the plant Amorphophallus konjac were potentially effective in menopausal osteoporosis due to their prebiotic attributes. The present work mainly studied the regulation of konjac oligosaccharides (KOS) on menopausal bone loss. Experiments were carried out in ovariectomized (OVX) rats, and various contents of KOS were correlated with diet. After 3 months of treatment, the degree of osteoporosis was determined by bone mineral density and femoral microarchitecture. The research data showed that the 8% dietary KOS significantly alleviated bone loss in OVX rats, as it promoted the bone trabecular number by 134.2% and enhanced the bone bending stiffness by 103.1%. From the perspective of the gut-bone axis, KOS promoted gut barrier repair and decreased pro-inflammatory cytokines. Besides, KOS promoted the growth of Bifidobacterium longum and restored Treg/Th17 balance in bone marrow. The two aspects contributed to decreased osteoclastogenic activity and thus inhibited inflammation-related bone loss. This work extended current knowledge of prebiotic inhibition on bone loss and provide an alternative strategy for osteoporosis prevention.

Network structure of complex interactions of premenstrual syndrome and influencing factors in young adult women.

BACKGROUND: In the transition phase from adolescence to adulthood, premenstrual syndrome (PMS) occurs more commonly, with a variety of symptoms. The occurrence of PMS may be the result of a combination of demographic, physiological, psychological and sociological factors. This study aimed to identify the central symptoms of PMS, and explored the complex influencing factors especially the one-to-one inter-relationships factors with specific symptoms. METHOD: This is a cross-sectional study conducted in mainland China. 3458 young adult women were assessed. Using the Premenstrual Syndrome Scale (PSS) to assess the PMS, and PSS score was over 6 divided into PMS group, and vice versa. Influencing factors were assessed by a set of self-reported questionnaire. Network analysis was used to examined the interplay of PMS, whilst also considering the influencing factors of PMS. RESULTS: In summary, 1479 participants were in PMS group. Anxiety had the highest strength centrality (1.12/1.09), shown higher centrality in the both network. Swelling of the hands or feet also shown higher strength centrality (0.89) in PMS group. PMS is associated with a higher history of dysmenorrhea, and neurotic personality. Neurotic personality - depressed mood/nervousness (0.27/0.23), history of dysmenorrhea - abdominal distension (0.21), had significantly higher weight than other edges in PMS group. CONCLUSION: Anxiety was the most central symptom in the network, and was closely associated with other symptoms like depressed mood, which provided additional evidence for the centrality of emotional features in PMS. Moreover, the influencing factors of PMS combined demographic, physiological, psychological, and sociological factors. According to the central symptoms and factors affecting the specific PMS symptoms in young adult women, targeted intervention is helpful to prevent and alleviate PMS. LIMITATION: Cross-sectional design cannot infer the directionality of the associations between variables. All data is self-reported with recall bias and the edge weights across the constructs of influencing factors and PMS were fairly small.

Efficacy of varenicline or bupropion and its association with nicotine metabolite ratio among smokers with COPD.

BACKGROUND AND OBJECTIVE: Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. METHODS: This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. RESULTS: Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). CONCLUSION: Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Diffusion kurtosis imaging of brain white matter alteration in patients with coronary artery disease based on the TBSS method.

Object: The aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion kurtosis imaging (DKI). Additionally, we aimed to investigate the potential correlation between DKI parameters and cognitive function. Materials and methods: A total of 28 CAD patients and 30 healthy controls (HC) were prospectively enrolled in our study. All participants underwent routine and diffusion sequences of head imaging. DKE software was utilized to generate various diffusion kurtosis imaging parameters (DKI), including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD). Nonparametric tests were conducted using tract-based spatial statistics (TBSS) to compare the parameter values between the two groups. The parameter values of the significantly different fiber tracts were extracted and correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Results: Compared to the HC group, patients with coronary artery disease exhibited significant reductions in FA values in the bilateral Superior corona radiata, bilateral Anterior corona radiata, bilateral Posterior corona radiata, corpus callosum, left Posterior thalamic radiation, right Posterior limb of internal capsule, Anterior limb of internal capsule, and Cerebral peduncle, as well as in the left Superior longitudinal fasciculus. Additionally, KFA values decreased in the bilateral Anterior corona radiata, bilateral Anterior limb of internal capsule, and Genu of the corpus callosum. The MK values decreased in the right Posterior corona radiata, Retrolenticular part of the internal capsule, Posterior thalamic radiation (including optic radiation), Superior longitudinal fasciculus, and left Posterior thalamic radiation (including optic radiation). Moreover, the RK values decreased in the bilateral Retrolenticular part of the internal capsule, right Posterior thalamic radiation (including optic radiation), and Superior longitudinal fasciculus, as well as in the left Superior longitudinal fasciculus and Posterior thalamic radiation (including optic radiation) (p < 0.01, TFCE corrected), while no significant differences were observed in other parameter values (p > 0.01, TFCE corrected). The FA values of the right posterior limb of the internal capsule (r = 0.610, p = 0.001) and the right cerebral peduncle (r = 0.622, p < 0.001) were positively correlated with MMSE scores. Additionally, a significant correlation between kurtosis and diffusion coefficient parameters (FA and KFA) was observed. Conclusion: CAD patients showed radial shrinkage and complexity of brain white matter microstructure. Whole-brain white matter analysis based on TBSS DKI can objectively reflect the characteristics of white matter damage in CAD patients, providing a basis for the auxiliary diagnosis of CAD with CI.

Proteomics Analysis Reveals the Underlying Factors of Mucilage Disappearance in Brasenia schreberi and Its Influence on Nutrient Accumulation.

Brasenia schreberi J.F. Gmel (BS) is rich in mucilage, which has diverse biological activities, and is utilized in the food and pharmaceutical industries due to its nutritional value. Proteomics analysis was employed to investigate the cause of mucilage disappearance in BS and its effect on nutrient accumulation. Among the 2892 proteins identified, 840 differentially expressed proteins (DEPs) were found to be involved in mucilage development. By comparing the expression patterns and functions and pathway enrichment, the DEPs mainly contributed to carbon and energy metabolism, polysaccharide metabolism, and photosynthesis. Our study also revealed positive correlations between mucilage accumulation and tryptophan metabolism, with high levels of indole-3-acetic (IAA) contributing to mucilage accumulation. Furthermore, environmental changes and particularly excessive nutrients were found to be detrimental to mucilage synthesis. Overall, in the absence of various stimuli in the growing environment, BS accumulates more nutrients within the plant itself instead of producing mucilage.

Ocular Biometry Features and Their Relationship with Anterior and Posterior Segment Lengths among a Myopia Population in Northern China.

Objectives: The study aims to explore the ocular biometry of a myopic population in Northern China, focusing specifically on anterior and posterior segment lengths. Methods: This is a cross-sectional study. The medical records of 3458 myopic patients who underwent refractive surgery were evaluated. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT) and other biometric parameters were measured using the IOL Master 700. The study determined the anterior segment length (ASL = ACD + LT), the posterior segment length (PSL = AL - ASL) and the ratio of ASL to PSL (ASL/PSL). Results: This study included 3458 eyes from 3458 myopic patients (1171 men and 2287 women). The mean age was 27.38 ± 6.88, ranging from 16 to 48 years old. The mean ASL was 7.35 ± 0.27 mm, and the mean PSL was 18.39 ± 1.18 mm. The ASL and PSL trends demonstrate an age-related increase for both genders, with notable gender-specific variations. Across most age groups, males typically exhibited higher ASLs and PSLs than females, with the exception of the 35-40 and 40-45 age groups. The ASL and PSL consistently increased with a rising AL. The AL strongly correlates with the PSL and negatively correlates with the ASL/PSL ratio. The ACD and LT moderately correlate with the ASL, but an increased LT does not imply a longer posterior segment. The CCT and SE show little correlation with axial eye parameters. Conclusions: Among Chinese myopic patients, a longer ASL and PSL were correlated with older age and the male gender. The AL strongly correlates positively with the PSL and negatively correlates with the ASL/PSL ratio. An elongation of the posterior segment may primarily account for an eyeball's lengthening.

Quantification of alkalinity of deep eutectic solvents based on (H-) and NMR.

Alkaline deep eutectic solvents (DESs) have been widely employed across diverse fields. A comprehensive understanding of the alkalinity data is imperative for the comprehension of their performance. However, the current range of techniques for quantifying alkalinity is constrained. In this investigation, we formulated a series of alkaline DESs and assessed their basicity properties through a comprehensive methodology of Hammett functions alongside 1H NMR analysis. A correlation was established between the composition, structure and alkalinity of solvents. Furthermore, a strong linear correlation was observed between the Hammett basicity (H-) of solvents and initial CO2 adsorption rate. Machine learning techniques were employed to predict the significant impact of alkaline functional components on alkalinity levels and CO2 capture capacity. This study offers valuable insights into the design, synthesis and structure-function relationship of alkaline DESs.

Clinical and radiological differentiation between Trousseau syndrome and cardiogenic embolism: a retrospective case-control study.

Background: Trousseau syndrome (TS) is a thromboembolic event in cancer patients caused by abnormalities in coagulation and fibrinolytic mechanisms. Acute multiple cerebral infarction (AMCI) is a rare form of TS. This study aimed to discuss the differentiation of clinical and radiographic characteristics between TS and cardiogenic embolism (CE) with AMCI as the main manifestation. Methods: We retrospectively analyzed 69 patients with TS-AMCI and 105 patients with CE-AMCI who were treated at Shandong Provincial Hospital between August 2018 and October 2022. The clinical baseline data, laboratory indices, and imaging characteristics of the two groups were compared. A logistic regression was used to analyze the risk factors of TS-AMCI, and receiver operating characteristic (ROC) curves were used to analyze the predictive value of the risk factors. Results: In relation to the clinical data, there were statistically significant differences between the two groups of patients in terms of the lipid and coagulation indices. D-dimer [odds ratio (OR) =4.459, 95% confidence interval (CI): 1.871-10.625; P=0.001] and triglyceride (OR =6.001, 95% CI: 2.375-15.165; P<0.001) were independent risk factors for TS-AMCI. In relation to the radiographic characteristics, the infarctions in the TS-AMCI group were widely distributed in multiple arterial supply areas [23 (33.3%) vs. 10 (9.5%); P<0.001]. More importantly, bilateral anterior + posterior circulation was also an independent risk factor for TS-AMCI (OR =15.005, 95% CI: 1.757-128.17; P=0.013). Conclusions: Unexplained AMCI in the cancer-prone age group, abnormalities in the lipid and D-dimer levels, and infarction foci involving multiple arterial blood supply areas suggested a high probability of TS.

Oxaloacetic acid induces muscle energy substrate depletion and fatigue by JNK-mediated mitochondrial uncoupling.

Fatigue is a common phenomenon closely related to physical discomfort and numerous diseases, which is severely threatening the life quality and health of people. However, the exact mechanisms underlying fatigue are not fully characterized. Herein, we demonstrate that oxaloacetic acid (OAA), a crucial tricarboxylic acid cycle intermediate, modulates the muscle fatigue. The results showed that serum OAA level was positively correlated with fatigue state of mice. OAA-treated induced muscle fatigue impaired the exercise performance of mice. Mechanistically, OAA increased the c-Jun N-terminal kinase (JNK) phosphorylation and uncoupling protein 2 (UCP2) levels in skeletal muscle, which led to decreased energy substrate and enhanced glycolysis. On the other hand, OAA boosted muscle mitochondrial oxidative phosphorylation uncoupled with energy production. In addition, either UCP2 knockout or JNK inhibition totally reversed the effects of OAA on skeletal muscle. Therein, JNK mediated UCP2 activation with OAA-treated. Our studies reveal a novel role of OAA in skeletal muscle metabolism, which would shed light on the mechanism of muscle fatigue and weakness.

Luteolin attenuates Staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway.

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by Staphylococcus aureus (S. aureus) and further clarified the possible molecular mechanisms. An S. aureus-induced endometritis model was established by the infusion of S. aureus into the uterus. Luteolin was intraperitoneally administered to mice 1 h before S. aureus treatment. The results showed that the mice of the S. aureus group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1ß, and IL-6 levels. These changes induced by S. aureus were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe2+ production and increased the production of GSH decreased by S. aureus. Luteolin prevented S. aureus-induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited S. aureus-induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on S. aureus-induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against S. aureus-induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.IMPORTANCEEndometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against S. aureus-induced endometritis and attempts to clarify the mechanism.

Optimizing FSH Concentration Modulation in the Short-Acting GnRH-a Long Protocol for IVF/ICSI: A Retrospective Study.

INTRODUCTION: Exogenous gonadotropin (Gn) is given to regulate follicle-stimulating hormone (FSH) levels to achieve optimal ovarian response in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The objective of this study was to analyze the optimal degree of change in FSH blood concentration with ovarian responsiveness in a short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol for IVF/ICSI. METHODS: This retrospective study was conducted at Changzhou Maternity and Child Health Hospital's Reproductive Center from May 2017 to May 2023. A total of 794 ovarian stimulation cycles for IVF/ICSI using the short-acting GnRH-a long protocol was included. Ovarian responsiveness was assessed based on the number of follicles > 14 mm on human chorionic gonadotropin (HCG) trigger day, refine-follicular output rate (Refine-FORT) and good quality embryos. Delta 1 referred to the change in FSH level between days 6-8 of gonadotropin usage and baseline FSH, while Delta 2 referred to the change in FSH level between HCG trigger day and days 6-8 of gonadotropin usage. Simple and multiple linear regression analysis were performed to adjust for confounding factors. RESULTS: The number of follicles > 14 mm on HCG trigger day was found to be the most suitable indicator for evaluating ovarian responsiveness compared to the number of follicles > 16 mm and the number of retrieved oocytes. When Delta 1 ranged from 1.94 to 3.37, the number of follicles > 14 mm on HCG trigger day was the highest. When Delta 1 ranged from 3.37 to 5.90, the Refine-FORT was the highest. However, when Delta 1 exceeded 5.90, the number of follicles > 14 mm on HCG trigger day, Refine-FORT and good quality embryo all significantly decreased. On the other hand, when Delta 2 was ≤ - 1.58, the number of follicles > 14 mm on HCG trigger day and the Refine-FORT were both the highest. CONCLUSION: This study identifies optimal Delta 1 and Delta 2 ranges for effective ovarian responsiveness in a short-acting GnRH-a long protocol for IVF/ICSI and introduces the novel measure of the number of follicles > 14 mm on HCG trigger day. The optimal range for Delta 1 was 1.94 to 3.37, and Delta 2 should be < - 1.58 for achieving a higher number and quality of oocytes.

Doublecortin-like kinase 3 (DCLK3) is associated with bad clinical outcome of patients with gastric cancer and regulates the ferroptosis and mitochondria function in vitro and in vivo.

BACKGROUND: Doublecortin-like kinase 3 (DCLK3), a member of tubulin superfamily, has been proved to be closely associated with the pathogenesis of numerous human tumors. However, the expression pattern and regulatory mechanisms of DCLK3 in gastric cancer (GC) remain unknown. MATERIALS AND METHODS: DCLK3 expression in GC cells was assessed by RT-qPCR and western blotting. The correlation between DCLK3 levels and the overall survival of GC patients was assessed via TCGA, ACLBI, and Kaplan-Meier plotter databases. Additionally, key proteins (TCF4) involved in the regulation of DCLK3 on GC progression were screened by ACLBI database. Cell proliferation, ferroptotic cell death, and oxidative stress markers were measured by EdU staining, immunofluorescence, ELISA, and western blotting assays. RESULTS: DCLK3 was upregulated in GC, and high DCLK3 expression was significantly associated with poor survival of GC patients. Here, DCLK3 knockdown reduced GC cell proliferation, induced ferroptotic cell death, and exacerbated oxidative stress level. Logistic regression analysis showed that TCF4 was an independent prognostic indicator of GC. Mechanistically, DCLK3 promoted TCF4 expression and subsequently upregulated the expression of TCF4 downstream target genes (c-Myc and Cyclin D1). Furthermore, DCLK3 overexpression enhanced GC cell proliferation, but mitigating ferroptotic cell death and oxidative stress. The regulatory mechanism may involve the upregulation of TCF4, c-Myc, and cyclin D1. CONCLUSIONS: Our research suggests that DCLK3 modulates the levels of iron and reactive oxygen and may involve regulation of TCF4 pathway, thereby promoting the GC cell growth, indicating that DCLK3 may use as a prognostic marker and therapeutic target for GC patients.

Treatment-induced menopause symptoms among women with breast cancer undergoing chemotherapy in China: a comparison to age- and menopause status-matched controls.

OBJECTIVE: Whether women with breast cancer experience more severe menopause symptoms than comparison women without a history of breast cancer diagnosis remains unclear. We aimed to investigate whether women with breast cancer undergoing chemotherapy experience more severe menopause symptoms than comparison women and explore various factors influencing menopause symptoms in women with breast cancer undergoing chemotherapy. METHODS: This cross-sectional observational study recruited 423 women with breast cancer undergoing chemotherapy and 1,829 community women without breast cancer. All participants completed a questionnaire assessing menopause symptoms using the Menopause Rating Scale and general characteristics (eg, sociodemographic and clinical data). Propensity score matching was used to reduce the confounders between the two groups. Student's t test or Mann-Whitney U test and chi-square tests were used to compare the differences in menopause symptoms between the two groups. Multivariate linear regression analysis was performed to explore various factors influencing menopause symptoms in women with breast cancer undergoing chemotherapy. RESULTS: After propensity score matching, 808 participants were included. The mean ages of women with breast cancer undergoing chemotherapy and comparison women were 49.58 and 49.10 years, respectively. Women with breast cancer undergoing chemotherapy experienced significantly more severe vasomotor symptoms than comparison women. However, comparison women had higher Menopause Rating Scale scores and more severe menopause symptoms than women with breast cancer undergoing chemotherapy. Age, occupational status, chemotherapy-induced amenorrhea, family history of cancer, chemotherapy stage, mindfulness, resiliency, and illness perception were associated with menopause symptoms in women with breast cancer undergoing chemotherapy. CONCLUSIONS: Vasomotor symptoms are prominent among women with breast cancer undergoing chemotherapy. Understanding the factors contributing to menopause symptoms is crucial for healthcare practitioners to develop supportive guidelines for the well-being of women with breast cancer undergoing chemotherapy.