Recently, the loss-of-function, heterozygous, and de novo mutations of the CTNNB1 gene have been proven to be partially responsible for intellectual disability in some patients. Herein, we report two unrelated children with neurodevelopmental disorder, abnormal facial features, speech impairments, microcephaly, and dystonia. Based on whole exome sequencing (WES), two new heterozygous and pathogenic mutations in exon 10 (c.1586dupA:p.Q530Afs*42) and exon 4 (c.257dup:p.Y86*) were identified in the CTNNB1 gene for the first time. These findings not only enrich the genetic spectrum of the CTNNB1 gene but also provide evidence for its role in neuronal development.
Obstract: Objective To study the applied value of the ratio of the serum Free Prostate Specific Antigen(FPSA) and Total Prostate Specific Antigen(TPSA) in patients with female breast disease.Methods Electrochemiluminescence was perfomed to measure the serum FPSA and TPSA level in 47 patients of breast cancer,34 women of benign breast diesae and 30 healthy women;and evaluating the diagnostic and prognostic value of the ratio of the F/T to the breast disease.Results As F/T 0.15,the positive diagnosis rate was 46.8%.Its ratio was much higher than single to detect contents of FPSA or TPSA.Conclusion Detecting the ratio of F/T will be important helpful to the diagnostic and prognostic value to the breast disease.
Gastric cancer is the fifth most common malignancy in the world with alow 5-year survival rate. To date, no study has investigated the prognostic role of the small mother against decapentaplegic (SMAD) in gastric cancer. The association of SMADs with overall survival (OS) of gastric cancer was analyzed on the online Kaplan-Meier (KM) plotter database. Clinical data such as stage, differentiation, gender, treatment, and Her2 mutation status of gastric cancer patients were analyzed. The (E)-SIS3 was used to inhibit SMAD3 expression in gastric cancer cells, and the effects of SMAD3 on gastric cancer cells were analyzed via real-time cellular analysis (RTCA), flow cytometry, colony formation, and immunofluorescence assay. The results showed that the high expression of three members of SMADs (SMAD1, SMAD2, SMAD4) was correlated with afavorable OS of gastric cancer patients. Meanwhile, SMAD3 expression level indicated highly differentiated cancer. We also observed that surgical treatment was associated with high expression level of SMAD1 and SMAD2. Besides, the effect of Her2 on gastric cancer was not noticeable. Moreover, (E)-SIS3 pharmacological assay revealed that inhibition of expression of SMAD3 suppressed the proliferation and migration ability of gastric cancer cells via inducing apoptosis. Collectively, these results demonstrate that the high expression level of three members of SMADs (SMAD1, SMAD2, and SMAD4) is significantly correlated with favorable OS of gastric cancer patients, which is opposite to SMAD3. Thus, SMADs regulate the differentiation of cancer and can be used to guide treatment decisions.
Cystatin C, the full name of cystatin C, is one of the most potent cathepsin inhibitors currently known, which can strongly inhibit cathepsin in lysosomes and regulate the level of intracellular proteolysis. Cystatin C plays a very broad role in the body. High temperature-induced brain injury leads to very serious damage to brain tissue, such as cell inactivation, brain tissue edema, etc. At this time, cystatin C can play a crucial role. Based on the research on the expression and role of cystatin C in high temperature-induced brain injury in rats, this paper draws the following conclusions: high temperature can cause very serious damage to the brain tissue of rats, which can seriously lead to death. Cystatin C has a protective effect on brain cells and cerebral nerves. When the brain is damaged by high temperature, cystatin C can relieve the damage of high temperature to the brain and protect brain tissue. In this paper, a detection method for cystatin C with more outstanding performance is proposed, and compared with the traditional detection method, the detection method in this paper is verified to have more accurate accuracy and excellent stability through comparative experiments. Compared with traditional detection methods, it is more worthwhile to use and is a better detection method.
Canine parvovirus (CPV) and feline parvovirus (FPV) are causative agents of diarrhea in dogs and cats, which manifests as depression, vomiting, fever, loss of appetite, leucopenia, and diarrhea in young animals. CPV and FPV can single or mixed infect cats and cause disease. To diagnose sick animals effectively, an effective virus diagnostic and genome typing method with high sensitivity and specificity is required. In this study, a conserved segment containing one SNP A4408C of parvovirus was used for real-time PCR amplification. Subsequently, data were auto-analyzed and plotted using Applied Biosystems® High Resolution Melt Software v3.1. Results showed that CPV and FPV can be detected simultaneously in a single PCR reaction. No cross-reactions were observed with canine adenovirus, canine coronavirus, and canine distemper virus. The assay had a detection limit of 4.2 genome copies of CPV and FPV. A total of 80 clinical samples were subjected to this assay, as well as to conventional PCR-sequence assay and virus isolation. Results showed that the percentage of agreement of the assay and other methods are high. In short, we have developed a diagnostic test for the accurate detection and differentiation of CPV and FPV in fecal samples, which is also cost effective.
The purpose of this cross-sectional study was to identify the current awareness about cervical cancer prevention among rural women in Luohe City as well as its potential influencing factors. Meanwhile, these data were expected to provide a theoretical basis for Luohe future cervical cancer prevention and therapy. Based on geographical distribution, 40 villages in Luohe City were randomly selected, and questionnaires were given to women in each village. In this study, a total of 4665 questionnaires were distributed, and 4561 valid questionnaires were returned, with a recovery rate of 97.98%. The average score was 4.06 ± 2.46 out of 10. It was found that women had a high awareness rate of cervical cancer screening (55.25%) but a low awareness rate of human papillomavirus (HPV) and HPV vaccine (10.17%). Moreover, univariate and multivariable analyses showed that age > 45 years, low household income, low education level, being a farmer, spouse unemployment, no pregnancy or birth delivery history, no family or personal history of cervical disease, and no previous complimentary 2-cancer screening (i.e., breast cancer and cervical cancer) were all factors influencing the cognitive level of rural women in Luohe City (P < .05). However, ethnicity, marital status, and spouse education level were not correlated with cognitive level (P > .05). In conclusion, low awareness of cervical cancer prevention among rural women in Luohe was correlated with individual, family, and social factors. So it was recommended to cultivate the rural population knowledge, optimize screening strategies, and conduct targeted cervical cancer prevention and treatment in rural regions.
Abstract Introduction: The intricate nature and varied forms of bladder urothelial carcinoma (BLCA) highlight the need for new signals to define tumor prognosis. Disulfidptosis, a novel cell death form, is closely linked to BLCA progression, prognosis, and treatment outcomes. Our current goal is to develop a novel disulfidptosis-related immune prognostic model to enhance BLCA treatment strategies. Methods RNA-seq data from TCGA included 419 patients, with clinical details and prognostic data (19 normal, 400 tumor samples). Weighted gene co-expression network analysis (WGCNA) identified disulfidptosis-related immune genes. Univariate, multivariate Cox, and LASSO regression established a disulfidptosis-related immune risk score. A nomogram combining risk score and clinical features predicted prognosis. Model performance was validated through curve analysis and independent prediction. Immune checkpoints, cell infiltration, and tumor mutation load were assessed. Differential gene enrichment analysis was conducted. Prognostic genes were validated via in vitro experiments. Results Eight immune genes related to disulfidptosis were identified and verified in BLCA prognosis. A prognostic model outperformed previous ones in predicting overall survival (OS) for high- and low-risk groups. Patients with low risk-scores had higher OS rates and mutation load expression compared to high risk-score patients. CD4 memory T cells, CD8 T cells, M1 macrophages, and resting NK cells were higher in the low-risk group. ICIS treatment may be more effective for the low risk-score group. High risk-score group exhibited stronger correlation with cancer malignant pathways. Knocking out TNFRSF12A inhibits BLAC cell proliferation and invasion, while overexpressing it has the opposite effect. Conclusions We constructed a novel risk score model combining disulfidptosis and immune genes with good prognostic prediction performance. We discovered and verified that the TNFRSF12A gene is an oncogene in BLAC, which may help provide personalized guidance for individualized treatment and immunotherapy selection for BLCA patients to a certain extent.
Introduction: ACT001 is widely used for the treatment of glioblastomas, breast cancers and leukemic and the mechanism underlying the effect is anti-inflammatory. However, whether ACT001 has any effects on acute respiratory distress syndrome (ARDS) is not clear. Objectives: To investigate whether ACT001 helps to reduce mortality and pneumonedema after ARDS, and explore whether the mechanism is related to balance autophagy and inflammatory response. Methods: In this study, a rat model based on CLP was used to explore the potency of ACT001 in ARDS. The expression of autophagy-related protein, lung injuries, cytokines as well as inflammatory related protein were assessed. Results: Compared with CLP group, ACT001 improved the survival rate, lung wet-to-dry weight ratio and morphology of lung cells. ACT001 activates autophagy, which is involved in the pathophysiologic process of sepsis, balancing the cytokine excessive release and lung injury in ARDS. Conclusion: ACT001 reduce mortality through improved autophagy and attenuate inflammatory after ARDS.
ABSTRACTBackground Exportin 1 (XPO1) inhibitors are being developed as a new agent for anti-cancer therapies. This study aimed to broadly portray the adverse event (AE) profile of selinexor, an XPO1 inhibitor, in actual clinical practice.Research design and methods Disproportionality analyses were conducted by calculating the information component and reporting odds ratio in VigiBase over different reporting periods. All selinexor-related AEs were classified by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities.Results A total of 116,443 AEs were identified in 2,608 patients that received selinexor. Patients with cardiac disorders had a higher propensity for death. Thirteen SOCs and 125 PTs were identified as having a potential connection with selinexor. Notably, 29 suspected signals detected in our study were defined as significant AEs by the European Medicines Agency, including febrile neutropenia, pancytopenia, and acute kidney injury. Attention should be paid to these AEs, despite most toxicities being manageable and reversible.Conclusions This study highlights a number of AEs associated with selinexor. Most toxicities are reversible but require careful management. The benefit of selinexor still outweighs the potential risks, indicating XPO1 inhibitors as promising agents.KEYWORDS: Disproportionality analysispharmacovigilanceselinexorSINEVigiBaseXPO1 Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contribution statementC Chen and X Guo conceptualized and designed the study, carried out the initial analysis, drafted the initial manuscript, and reviewed and revised the manuscript. X Miao reviewed and revised the manuscript from the perspective of clinical practice, conceptualized and designed the study, improved the language and clarity of the article. J Xu designed the data collection instruments, supervised data collection, Y Zheng, L Chi and X Chen checked all the data analysis and reviewed and revised the manuscript. J Liang, H Zhang and L Wei collected data, coordinated the initial data analysis, and reviewed and revised the manuscript. X Ye, and J He conceptualized and designed the study, coordinated, and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.AcknowledgmentsThe data provided by VigiBase come from a variety of sources. In all reports, the likelihood of causality is different. This information does not represent the opinion of the WHO. At the same time, the authors would like to thank the research department of Uppsala Monitoring Center (Uppsala, Sweden) for their help in data extraction.Data availability statementData is available on request from the Uppsala Monitoring Centre of the WHO Program for International Drug Monitoring (https://www.who-umc.org/vigibase/vigibase/).Additional informationFundingThis paper was funded by the National Nature Science Foundation of China (No. 82073671), the Big Data and Artificial Intelligence Application and the Military Key Discipline Construction Project (Health Service Naval Health Service Organization and Command, No. 03).
Objective To investigate the relationship between high sensitivity C reactive protein(hs-CRP)level and peripheral artery disease in patients with type 2 diabetes mellitus(T2DM).Methods 120 patients with T2DM were enrolled in this study,58 paitiens of them were with peripheral artery diseases(observed group),as well as 62 patients of them without peripheral artery diseases(control group).The levels of hs-CRP in two groups were measured.Results The level of hs-CRP in the observed group were significantly higher than that in the control group.The level of hs-CRP was independently associated with the development of peripheral artery disease in patients with T2DM.Conclusions The development of T2DM is associated with hs-CRP.Increase of hs-CRP level is an independent risk factor for peripheral artery disease in patients with T2DM.
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