Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective:To explore the clinical efficacy and safety of a multimodal treatment regimen integrating radiotherapy, chemotherapy, and immunotherapy in patients with human epidermal growth factor receptor 2 (HER2) -negative locally advanced or advanced gastric cancer.Methods:A total of 34 patients with unresectable, HER2-negative, locally advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma admitted to the Affiliated Cancer Hospital of Guizhou Medical University from September 2021 to March 2024 were selected as study objects. Participants received one cycle of either XELOX regimen (capecitabine + oxaliplatin) or SOX regimen (S-1 + oxaliplatin) with immunotherapy (sintilimab or nivolumab) . The process was succeeded by radiotherapy targeted at the primary G/GEJ tumor and regional lymph nodes. In selected cases, sequential radiotherapy was also administered for distant metastases. The primary endpoint was objective response rate (ORR) , and secondary endpoints were disease control rate (DCR) , clinical symptom response, changes in Karnofsky performance status (KPS) score, progression-free survival (PFS) , and adverse reactions. Clinical efficacy was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Adverse reactions were assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and the Chinese Society of Clinical Oncology guidelines for management of immune checkpoint inhibitor-related toxicity. With a median follow-up of 7 months (range: 2.3 to 30 months) , the final evaluation considered the best response documented throughout follow-up. Survival curves were constructed utilizing Kaplan-Meier analysis.Results:By the end of follow-up, an overall ORR of 58.8% (20/34) and DCR of 70.6% (24/34) were observed. The ORR of lesions by radiotherapy reached 73.8% (48/65) and the DCR reached 92.3% (60/65) . Univariate analysis showed that the ORR of female patients (84.6%, 11/13) was higher than that of male patients (42.9%, 9/21) , and the ORR of patients with distant lymph node metastasis alone (83.3%, 15/18) was higher than that of patients with distant lymph node metastasis combined with organ metastasis or organ metastasis alone (18.2%, 2/11) , with statistically significant differences ( P=0.030; P=0.010) . There were no statistically significant differences in ORR among patients with different age ( P=0.487) , KPS score ( P=0.198) , primary tumor location ( P=0.280) , histological differentiation ( P=0.668) , chemotherapy regimen ( P=0.728) , or immunotherapy regimen ( P>0.999) . Twenty-two of 23 (95.7%) patients with upper abdominal pain were relieved, 10 of 21 (47.6%) patients with appetite loss were relieved, 15 of 17 patients with upper abdominal distension were relieved, 13 of 14 patients with melena were relieved, 6 of 7 patients with eating obstruction were relieved, 3 of 4 patients with metastatic site pain were relieved, and 2 patients with hematemesis were relieved. KPS score enhanced in 82.4% (28/34) of patients, remained stable in 11.8% (4/34) , and declined in 5.8% (2/34) . The median PFS of the 34 patients was 7.9 months. The most common adverse reactions during radiotherapy combined with chemotherapy and immunotherapy were hematological adverse reactions, in which neutropenia accounted for the highest proportion (91.2%, 31/34) , followed by anemia (50.0%, 17/34) . Fatigue was the most common non-hematological adverse reaction (50.0%, 17/34) , followed by nausea and vomiting (26.5%, 9/34) . The adverse reactions of 6 patients receiving immune monotherapy maintenance were anemia, hypothyroidism, transaminase elevation, proteinuria, fatigue, and rash, all of which were grade 1-2. Conclusions:Radiotherapy combined with chemotherapy and immunotherapy shows good short-term clinical efficacy in patients with HER2-negative locally advanced or advanced gastric cancer, and the overall adverse reactions are tolerable. Female or patients with distant lymph node metastasis alone may be the preferred population for this study protocol.

Humans ; Parkinson Disease/diagnosis* ; Machine Learning