The relationship between serum uric acid and gastrointestinal bleeding in peritoneal dialysis patients: a propensity score analysis.

PURPOSE: Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients. METHODS: A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan-Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups. RESULTS: According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001-3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid. CONCLUSION: The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

Efficacy of PD-1/PD-L1 blockade immunotherapy in recurrent/metastatic high-grade neuroendocrine carcinoma of the cervix: A retrospective study.

Although high-grade neuroendocrine carcinoma of the cervix (HGNECC) accounts for less than 1 % of all cervical cancers, it exhibits marked aggressiveness and resistance to radiation and chemotherapy. We retrospectively investigated the efficacy of immunotherapy for recurrent/metastatic HGNECC in a real-world setting. From September 2016 to December 2022, a total of 29 patients with HGNECC accepted PD-1/PD-L1 inhibitors; of these, six cases (20.7 %) were PD-L1 positive (combined positive score ≥1). According to their primary treatment, the patients were assigned to either a surgery group (n = 14) or a non-surgery group (n = 15). In the surgery group, four patients received anti-PD-1 therapy immediately after surgery, while six, two, one, and one patients started immunotherapy after the first, second, third, and forth recurrence, respectively. In the non-surgery group, seven patients started immunotherapy as part of their primary treatment, while the other four, two, and two patients received anti-PD-1 drugs as the second, third, and forth lines of treatment, respectively. The seven-patient group showed longer progression-free survival after immunotherapy (PFSi) and overall survival than those of their counterparts (P = 0.085 and 0.08, respectively), while this benefit was not observed in other subgroups. No significant correlation was observed between PD-L1 and PFSi expression. Interestingly, one patient with a high tumor mutation burden (TMB-H) had a long PFSi of 26 months and experienced no recurrence until the last follow-up. Based on these findings, we propose that PD-1/PD-L1 inhibitors may prolong the survival of patients with HGNECC who start immunotherapy as the first-line of treatment. This indicates that early immunotherapy may be a better choice for this challenging malignancy. Moreover, the predictive role of TMB-H in immunotherapeutic outcomes requires further investigation.

Effective Treatment with Venetoclax and Hypomethylating Agents for the Coexistence of Multiple Myeloma and Acute Myeloid Leukemia: A Case Report and Literature Review.

OBJECTIVE: Multiple myeloma (MM) and Acute myeloid leukemia (AML) are distinct hematologic malignancies originating from different cell lineages. Their coexistence is extremely rare, and current treatment approaches are even more so. Therefore, exploring the clinical features of their coexistence and the promising treatment strategy is worthwhile. CASE REPORT: We described three cases involving the coexistence of MM and DNMT3A-mutant AML, two of which presented simultaneous occurrences, while Case 3 had secondary AML about 70 months after the MM. DISCUSSION: All cases exhibited DNMT3A mutations, which characterized by one missense mutation and two frameshift mutations; all were likely loss of function mutations. Among them, two patients were treated with Venetoclax-based regimens and achieved favorable effects. The patients were alive for 62,38 and 103 months. CONCLUSIONS: Clonal hematopoiesis of DNMT3A may have a crucial role in the coexistence of MM and AML and Venetoclax-based regimens reveal favorable treatment responses. However, drug resistance still needs to be considered, and further research is required to elucidate the underlying mechanisms and treatment strategies.

Neutrophil activation and related disrupted frontolimbic circuit may contribute to cognitive progression of minimal depressive symptoms in non-dementia elderly.

BACKGROUND: As a more common but easily neglected disorder, minimal depressive symptoms (MDS), it is unclear whether and why it increases the risk of cognitive progression in non-dementia elderly. METHODS: The Alzheimer's disease Neuroimaging Initiative (ADNI) database was used to assign 1065 non-dementia elderly into normal control (n = 380) and MDS (n = 685) groups via the Geriatric Depression Scale (GDS). Blood neutrophils, transcriptomics and metabolomics, cerebrospinal fluid (CSF) proteomics, and magnetic resonance imaging (MRI) data were analyzed. RESULTS: MDS was found to increase the risk of cognitive progression independently of multiple psychological symptoms. Increased levels of blood neutrophils were associated with cognitive progression in MDS, as supported by neutrophil-related pathways by transcriptomic enrichment analysis and multi-omics joint analysis. A disrupted frontolimbic circuit was associated with neutrophil activation in MDS. LIMITATIONS: The heterogeneity of the sample limited the generalizability of results, and the lack of follow-up data limited the research on the mechanism of neutrophil activation influencing cognitive function in MDS. CONCLUSIONS: Cognitive progression occurs as early as the MDS stage. And this phenomenon may attribute to the neutrophil activation and the related disrupted frontolimbic circuit.

Mental health literacy and help-seeking intention among Chinese elite athletes: the mediating roles of stigma and social support.

Objectives: Considering the importance of mental health help-seeking, researchers have closely examined the relationship between mental health literacy (MHL) and help-seeking intention (HSI). Furthermore, the high impact of stigma and the potential value of social support on HSI have been recognised. However, the relationship between these variables has not been fully tested within the context of Chinese elite athletes. This study addressed this gap by examining the relationship between MHL and HSI. Furthermore, it explored the mediating effects of public stigma, self-stigma, and social support on the relationship between MHL and HSI among Chinese elite athletes. Methods: 450 Chinese elite athletes (M age = 18.12, SD = 3.20, 46.2% female) self-reported their MHL, public stigma, self-stigma, social support, and HSI. Mediation analysis was conducted using the bootstrap approach of the PROCESS macro version 3.3 of SPSS 25. Results: The results showed a significant positive correlation between MHL and HSI (r = 0.348). The results also demonstrated that MHL was a predictor of HSI (ß = 0.337, 95%CI [0.249, 0.425], p < 0.001). Furthermore, 1) the indirect effect of MHL → public stigma→HSI was 0.024 and a 95%CI [0.003, 0.053]. Specifically, MHL predicted public stigma (Estimate = -0.151, 95%CI [-0.187, -0.045], p < 0.001), and public stigma predicted HSI (Estimate = -0.161, 95%CI [- 0.549, -0.164], p < 0.001); 2) the indirect effect of MHL → self-stigma→ HSI was 0.016 and 95%CI [0.002, 0.038]. Specifically, MHL predicted self-stigma (Estimate = -0.137, 95%CI [-0.069, -0.013], p < 0.01), and self-stigma predicted HSI (Estimate = -0.120, 95%CI [-1.181, -0.186], p < 0.01); as well as 3) the indirect effect of MHL → social support→HSI was 0.029 and a 95%CI [0.009, 0.055]. Specifically, MHL predicted social support (Estimate = 0.208, 95%CI [0.018, 0.047], p < 0.001), and social support predicted HSI (Estimate = 0.141, 95%CI [0.578, 2.442], p < 0.01). Additionally, the direct effects from MHL to HSI is (ß = 0.452, 95%CI [0.304, 0.600], p < 0.001). Conclusion: Our findings provide empirical support for the roles of public stigma, self-stigma, and social support as mechanisms of behavioural change in MHL interventions. These factors increase HSI among elite athletes. Future studies should further test these mediating effects using experimental designs.

Specific isolation and quantification of PD-L1 positive tumor derived exosomes for accurate breast cancer discrimination via aptamer-functionalized magnetic composites and SERS immunoassay.

PD-L1 positive tumor derived exosomes (TEXsPD-L1) play a significant role in disease progression, tumor metastasis and cancer immunotherapy. However, the overlap of PD-L1 between TEXs and non-tumor derived exosomes (non-TEXs) restricts the specific isolation and quantification of TEXPD-L1 from clinical samples. Herein, a new aptamer-functionalized and hydrophilic immunomagnetic substrate was designed by decorating generation 5 polyamidoamine dendrimers (G5 PAMAM), zwitterionic trimethylamine N-oxide (TMAO) and EpCAM (Epithelial cell adhesion molecule) aptamers on magnetic cores sequentially (Fe3O4@PAMAM@TMAO@Aptamer, named as FPTA) for rapid target and efficient capture of TEXs. The FPTA substrate gathered excellent characters of strong magnetic responsiveness of Fe3O4, abundant affinity sites of PAMAM, strong hydrophilicity of TMAO and enhanced affinity properties of EpCAM aptamers. Because of these advantages, FPTA can isolate TEXs quickly within 30min with high capture efficiency of 90.5 % ± 3.0 % and low nonspecific absorption of 8.2 % ± 2.0 % for non-TEXs. Furthermore, PD-L1 (Programmed cell death-ligand 1) positive TEXs (TEXsPD-L1) from the captured TEXs were recognized and quantitatively analyzed by utilizing SERS (surface-enhanced Raman spectroscopy) reporter molecules 4-NTP (4-Nitrothiophenol) on PD-L1 aptamers-functionalized gold immunoaffinity probe. The signal of TEXsPD-L1 was converted to SERS signal of 4-NTP at 1344 cm-1 which exhibited a linear correlation to concentration of TEXsPD-L1(R2 = 0.9905). With these merits, this strategy was further applied to clinical plasma samples from breast cancer (BC) patients and healthy controls (HC), exhibited an excellent diagnosis accuracy with area under curve (AUC) of receiver operating characteristic (ROC) curve reaching 0.988. All these results demonstrate that the FPTA immunomagnetic substrate combined with SERS immunoaffinity probe may become a generic tool for specific isolation and quantitative analysis of PD-L1 positive tumor-derived exosomes in clinics.

CXCL9/CXCL10 as biomarkers the monitoring of treatment responses in Pulmonary TB patients: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a persistent threat to global public health and traditional treatment monitoring approaches are limited by their potential for contamination and need for timely evaluation. Therefore, new biomarkers are urgently required for monitoring the treatment efficacy of TB. METHODS: This study aimed to elucidate the levels of CXCL10 and CXCL9 in pulmonary TB patients who underwent anti-TB treatment. The data was acquired from five databases, including PubMed, Ovid, Web of Science, Embase, and the Cochrane Library. A meta-analysis of CXCL10 data from all time points was conducted. Furthermore, a trend meta-analysis of temporal data of CXCL10 and CXCL9 from multiple time points was also performed. RESULTS: It was revealed that patients who responded poorly to anti-TB treatment had higher serum levels relative to those who responded well (SMD: 1.23, 95% CI: -0.37-2.84) at the end of intensive treatment (2 months). Furthermore, heterogeneity was observed in these results, which might be because patients with a prior history of TB and different treatment monitoring methods than those selected in this study were also included. The analysis of alterations in CXCL10 and CXCL9 levels since the last collection time points indicated that their levels reduced with time. CONCLUSION: In summary, the study revealed that reductions in CXCL10 levels during the first two months of anti-TB treatment are correlated with treatment responses. Furthermore, decreasing levels of CXCL9 during the treatment suggest that it may also serve as a biomarker with a similar value to CXCL10. Future in-depth studies are thus warranted to further probe the relevance of CXCL10 and CXCL9 in monitoring the treatment efficacy of TB.

Comprehensive assessment of the climatic and vegetation impacts of wind farms on grasslands: A case study in inner Mongolia, China.

Although wind power contributes to the reduction of greenhouse gas emissions, it also has significant impacts on the local climate and vegetation. Exploring these impacts is important for the sustainable development of wind power. Therefore, based on moderate-resolution imaging spectroradiometer (MODIS) data and other remote sensing data from 2003 to 2022, this paper investigated the impacts of 101 grassland wind farms (WFs) in Inner Mongolia on land-atmosphere water and heat exchange, vegetation growth, ecosystem primary productivity, and vegetation structural characteristics during the growing season and revealed the spatial distribution patterns of the impacts of WFs as well as differences between different types of grasslands. The results indicated that WFs increased the nighttime land surface temperature (LST), decreased evapotranspiration (ET), inhibited vegetation growth, decreased gross primary productivity (GPP), and reduced the leaf area index (LAI) in growing season grasslands. This effect varied across different types of grasslands and showed significant complexity. In terms of land-atmosphere water and heat exchange, nighttime LST increases and ET decreases were significant in the typical steppe but not in the meadow steppe. In terms of vegetation change, meadow steppe had the most inhibited vegetation growth and the greatest reduction in GPP. In terms of the impact range, WFs on typical steppe and meadow steppe have opposite effects on vegetation growth and ecosystem primary productivity inside and outside of them, i.e., they inhibit vegetation growth and reduce GPP inside the WF areas but promote vegetation growth and increase GPP outside the WF areas. Compared with previous studies, this study analyzed multiple climate and vegetation indicators based on many WF samples, which reduced the uncertainty associated with a single sample and provided more comprehensive and comparable observations of different types of grasslands. These findings can help to balance the relationship between wind power development and ecological protection.

Associations between different insulin resistance indices and the risk of all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study's aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. METHODS: Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride-glucose (TyG) index, triglyceride-glucose/body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. RESULTS: Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG-BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261-2.000; HR 1.428, 95% CI 1.067-1.910; HR 1.431, 95% CI 1.105-1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. CONCLUSION: Significant associations were found between the TyG index, TyG-BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Nanoemulsion based lipid nanoparticles for effective demethylcantharidin delivery to cure liver cancer.

Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit-8 (CCK-8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor-bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor-targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion-based lipid nanoparticle (NLNs)-efficient DEM delivery to treat liver cancer.

Associations of Reallocating Sedentary Time to Physical Activity and Sleep with Physical and Mental Health of Older Adults.

INTRODUCTION: Twenty-four-hour movement behaviors: moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep are crucial factors affecting older adults' health. Using a compositional data analysis approach, this study examined the associations of time spent in these four movement behaviors with cardiometabolic health, physical fitness, and mental health among older adults. Furthermore, this study identified the estimated changes in aforementioned health outcomes by reallocating SB time to other movement behaviors. METHODS: A population-based cross-sectional study of 4562 participants (67.68 ± 5.03 yr; 55.8% female) were implemented in Hubei China between July 25 and November 19, 2020. Measures included demographics, movement behaviors, cardiometabolic indicators (body mass index, waist circumference, waist-hip ratio, percentage body fat, systolic and diastolic blood pressure), physical fitness, and mental health outcomes (depressive symptoms and loneliness). Compositional data analyses were implemented in R. RESULTS: MVPA and sleep time were associated with greater health outcomes (all P < 0.001), except blood pressure ( P = 0.13-0.83). LPA time was associated with waist circumference ( B = 0.313, P = 0.009), waist-hip ratio ( B = 0.003, P = 0.003), physical fitness ( B = 0.36, P < 0.001), and mental health indicators (both P < 0.001). Reallocating 30-min SB to MVPA and sleep was associated with predicated improvements in all health outcomes, except blood pressure, whereas reallocating 30-min SB to LPA resulted in predicted improvements in physical fitness (0.187 units), depressive symptoms (-0.264 units), and loneliness (-0.395 units). For dose-effect relationships, reallocating 5-60 min of SB to MVPA showed greatest benefits for all health outcomes. CONCLUSIONS: This study provides timely empirical evidence for future interventions and policymaking on promoting healthy aging during the post-COVID-19 era. The findings underline the importance of including 24-h movement behaviors in future health promotion among older adults.

Adherence to 24-Hour Movement Guidelines Among Chinese Older Adults: Prevalence, Correlates, and Associations With Physical and Mental Health Outcomes.

BACKGROUND: It is known that 24-hour movement behaviors, including physical activity (PA), sedentary behavior (SB), and sleep, are crucial components affecting older adults' health. Canadian 24-hour movement guidelines for older adults were launched in 2020, emphasizing the combined role of these 3 movement behaviors in promoting older adults' health. However, research on the prevalence and correlates of guideline adherence and its associations with health-related outcomes is limited, especially among Chinese older adults. OBJECTIVE: This study aimed to investigate the prevalence and correlates of meeting 24-hour movement guidelines among Chinese older adults. Furthermore, this study aimed to examine the associations of guideline adherence with older adults' physical and mental health outcomes. METHODS: Using a stratified cluster random sampling approach, a total of 4562 older adults (mean age 67.68 years, SD 5.03 years; female proportion: 2544/4562, 55.8%) were recruited from the latest provincial health surveillance of Hubei China from July 25 to November 19, 2020. Measures included demographics, movement behaviors (PA, SB, and sleep), BMI, waist circumference, waist-hip ratio (WHR), percentage body fat (PBF), systolic and diastolic blood pressure, physical fitness, depressive symptoms, and loneliness. Generalized linear mixed models were employed to examine the associations between variables using SPSS 28.0 (IBM Corp). RESULTS: Only 1.8% (83/4562) of participants met all 3 movement guidelines, while 32.1% (1466/4562), 3.4% (155/4562), and 66.4% (3031/4562) met the individual behavioral guidelines for PA, SB, and sleep, respectively. Participants who were older, were female, and lived in municipalities with lower economic levels were less likely to meet all 3 movement guidelines. Adhering to individual or combined movement guidelines was associated with greater physical fitness and lower values of BMI, waist circumference, WHR, PBF, depressive symptoms, and loneliness, with the exception of the relationship of SB+sleep guidelines with loneliness. Furthermore, only meeting SB guidelines or meeting both PA and SB guidelines was associated with lower systolic blood pressure. CONCLUSIONS: This is the first study to investigate adherence to 24-hour movement guidelines among Chinese older adults with regard to prevalence, correlates, and associations with physical and mental health outcomes. The findings emphasize the urgent need for promoting healthy movement behaviors among Chinese older adults. Future interventions to improve older adults' physical and mental health should involve enhancing their overall movement behaviors and should consider demographic differences.

Electronic Health Literacy Scale-Web3.0 for Older Adults with Noncommunicable Diseases: Validation Study.

BACKGROUND: In the current digital era, eHealth literacy plays an indispensable role in health care and self-management among older adults with noncommunicable diseases (NCDs). Measuring eHealth literacy appropriately and accurately ensures the successful implementation and evaluation of pertinent research and interventions. However, existing eHealth literacy measures focus mainly on individuals' abilities of accessing and comprehending eHealth information (Web1.0), whereas the capabilities for web-based interaction (Web2.0) and using eHealth information (Web3.0) have not been adequately evaluated. OBJECTIVE: This study aimed to examine the reliability, validity, and measurement invariance of the eHealth Literacy Scale-Web3.0 (eHLS-Web3.0) among older adults with NCDs. METHODS: A total of 642 Chinese older adults with NCDs (mean age 65.78, SD 3.91 years; 55.8% female) were recruited in the baseline assessment, of whom 134 (mean age 65.63, SD 3.99 years; 58.2% female) completed the 1-month follow-up assessment. Baseline measures included the Chinese version of the 24-item 3D eHLS-Web3.0, the Chinese version of the 8-item unidimensional eHealth Literacy Scale (eHEALS), and demographic information. Follow-up measures included the 24-item eHLS-Web3.0 and accelerometer-measured physical activity and sedentary behavior. A series of statistical analyses, for example, Cronbach α, composite reliability coefficient (CR), confirmatory factor analysis (CFA), and multigroup CFA, were performed to examine the internal consistency and test-retest reliabilities, as well as the construct, concurrent, convergent, discriminant, and predictive validities, and the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence. RESULTS: Cronbach α and CR were within acceptable ranges of 0.89-0.94 and 0.90-0.97, respectively, indicating adequate internal consistency of the eHLS-Web3.0 and its subscales. The eHLS-Web3.0 also demonstrated cross-time stability, with baseline and follow-up measures showing a significant intraclass correlation of 0.81-0.91. The construct validity of the 3D structure model of the eHLS-Web3.0 was supported by confirmatory factor analyses. The eHLS-Web3.0 exhibited convergent validity with an average variance extracted value of 0.58 and a CR value of 0.97. Discriminant validity was supported by CFA results for a proposed 4-factor model integrating the 3 eHLS-Web3.0 subscales and eHEALS. The predictive validity of the eHLS-Web3.0 for health behaviors was supported by significant associations of the eHLS-Web3.0 with light physical activity (ß=.36, P=.004), moderate to vigorous physical activity (ß=.49, P<.001), and sedentary behavior (ß=-.26, P=.002). Finally, the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence was supported by the establishment of configural, metric, strong, and strict invariances. CONCLUSIONS: The present study provides timely empirical evidence on the reliability, validity, and measurement invariance of the eHLS-Web3.0, suggesting that the 24-item 3D eHLS-Web3.0 is an appropriate and valid tool for measuring eHealth literacy among older adults with NCDs within the Web3.0 sphere.

Primary ovarian cancer combined with primary fallopian tube cancer: A case report.

BACKGROUND: Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer with a low incidence rate. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes. Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system. There are only a few reports in the literature, but the mortality rate is very high. But in clinical practice, fallopian tube cancer is very common, but in most cases, it is classified as ovarian cancer. CASE SUMMARY: We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment. The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube. No special treatment was performed after the surgery, and the patient was instructed to undergo regular follow-up without any signs of disease progression. CONCLUSION: The prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence.

[Effect of TP53 Allelic State on Clinical Performance and Prognosis of Patients with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the clinical significance of TP53 allelic state in patients with myelodysplastic syndromes (MDS). METHODS: The clinical data of 858 MDS patients who underwent second-generation sequencing (NGS) testing in the First Affiliated Hospital of Soochow University from January 2019 to December 2021 were retrospectively analyzed. RESULTS: The median age of the patients was 52 years old, and median follow-up time was 23.8 (0.4-109.6) months. Four hundred and one patients (46.7%) had at least one chromosomal abnormality, including 106 complex karyotypes and 78 monosomal karyotypes. A total of 103 cases of TP53 mutations were identified, with a mutation rate of 12%. Compared with TP53 wild-type, various types of chromosomal abnormalities were significantly more common in patients with TP53 mutations (all P < 0.001). Patients with TP53 mutations had lower hemoglobin levels, lower platelet counts and higher percentage of bone marrow primitive cell compared with TP53 wild type (all P < 0.05), and significantly shorter overall survival (OS). Among 97 evaluable patients, 33 cases (34%) were mono-allelic TP53 mutation, while 64 cases were bi-allelic TP53 mutation. Patients in bi-allelic TP53 mutation subgroup had a higher proportion of chromosomal abnormalities and a lower number of co-mutations compared with mono-allelic TP53 mutation. The median OS was 33.6 months in patients with mono-allelic state and only 11.4 months in patients with bi-allelic state (HR=2.138, 95%CI : 1.053-4.343, P >0.05). Median OS was not reached in TP53 wild-type patients, and there was a significant difference in OS among TP53 wild-type, mono-allelic and bi-allelic TP53 mutation patients (P < 0.001). Multivariable Cox regression analysis showed that bi-allelic TP53 was an independent predictor of poor outcomes (HR=2.808, 95%CI : 1.487-5.003, P =0.001), while mono-allelic TP53 mutation and wild-type TP53 were not. CONCLUSION: Patients with TP53 mutations have a poor prognosis, and bi-allelic TP53 mutations have a worse prognosis compared with mono-allelic TP53 mutations and independently affect the prognosis of MDS patients.

Mindfulness and acceptance-based training for elite adolescent athletes: a mixed-method exploratory study.

Objectives: This study aimed to examine the effectiveness of a specifically designed mindfulness-acceptance-insight-commitment (MAIC) training program on relevant psychological factors (i.e., mindfulness, acceptance, performance-related satisfaction) as well as sport training performance for elite adolescent athletes from Hong Kong. And it also aimed to explore the athletes' real experiences (i.e., receptiveness and perceptions) of completing the MAIC program. Methods and design: The mixed-method was used in this study, including a randomized controlled trial (RCT) and a qualitative exploration. The RCT employed a 2 (groups) x 3 (data collection points) design involving 40 elite adolescent athletes from the Hong Kong Sports Institute (HKSI). These athletes were randomly assigned to either the MAIC training group (MT; n = 20, Mage = 15.65) or the control group (CG; n = 20, Mage = 15.85) to further test the effectiveness of the MAIC intervention on mindfulness, acceptance, performance-related satisfaction, and sport training performance. Subsequent to the RCT, the qualitative exploration was used to explore the athletes' real experiences towards the MAIC program. In the qualitative exploration, all athletes who participated in the MAIC program were invited to participate in voluntary semi-structured interviews. Of these, 14 athletes chose to take part in the interviews. The RCT employed a 2×3 mixed-design ANOVA, while thematic analysis was applied to the qualitative exploration. Results: The results revealed that the MAIC training program significantly enhanced athletes' mindfulness, acceptance, satisfaction with performance, and sport training performance. However, these effects diminished at the follow-up assessment compared to post-training. Notably, the acceptance level of MT athletes did not significantly differ from CG athletes at the follow-up assessment. Additionally, the qualitative analysis identified four key dimensions: (a) Attitude towards MAIC training, (b) Reflection on the MAIC learning process, (c) Outcomes of MAIC training, and (d) Recommendations for future MAIC training. Overall, the qualitative findings complemented and reinforced the quantitative results, offering deeper insights into athletes' experiences and valuable suggestions for further enhancing the MAIC program. Conclusion: The findings suggested that the specifically designed MAIC training program in this study effectively enhanced sport training performance and various psychological factors among elite adolescent athletes from Hong Kong. Nevertheless, further investigations are still required to comprehensively evaluate and further develop the MAIC training program.

A prediction model for prognosis of nephrotic syndrome with tuberculosis in intensive care unit patients: a nomogram based on the MIMIC-IV v2.2 database.

Background: Currently, a scarcity of prognostic research exists that concentrates on patients with nephrotic syndrome (NS) who also have tuberculosis. The purpose of this study was to assess the in-hospital mortality status of NS patients with tuberculosis, identify crucial risk factors, and create a sturdy prognostic prediction model that can improve disease evaluation and guide clinical decision-making. Methods: We utilized the Medical Information Mart for Intensive Care IV version 2.2 (MIMIC-IV v2.2) database to include 1,063 patients with NS complicated by TB infection. Confounding factors included demographics, vital signs, laboratory indicators, and comorbidities. The Least Absolute Shrinkage and Selection Operator (LASSO) regression and the diagnostic experiment the receiver operating characteristic (ROC) curve analyses were used to select determinant variables. A nomogram was established by using a logistic regression model. The performance of the nomogram was tested and validated using the concordance index (C-index) of the ROC curve, calibration curves, internal cross-validation, and clinical decision curve analysis. Results: The cumulative in-hospital mortality rate for patients with NS and TB was 18.7%. A nomogram was created to predict in-hospital mortality, utilizing Alb, Bun, INR, HR, Abp, Resp., Glu, CVD, Sepsis-3, and AKI stage 7 days. The area under the curve of the receiver operating characteristic evaluation was 0.847 (0.812-0.881), with a calibration curve slope of 1.00 (0.83-1.17) and a mean absolute error of 0.013. The cross-validated C-index was 0.860. The decision curves indicated that the patients benefited from this model when the risk threshold was 0.1 and 0.81. Conclusion: Our clinical prediction model nomogram demonstrated a good predictive ability for in-hospital mortality among patients with NS combined with TB. Therefore, it can aid clinicians in assessing the condition, judging prognosis, and making clinical decisions for such patients.

The pseudogene GBP1P1 suppresses influenza A virus replication by acting as a protein decoy for DHX9.

Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.