ABSTRACT
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
ABSTRACT
AIM: This study aimed to investigate whether computed tomography (CT)-measured erector spinae parameters (ESPs) have diagnostic, severity assessment, and prognostic predictive value in uremic sarcopenia (US). MATERIALS AND METHODS: A total of 202 uremic patients were enrolled and divided into two groups: a control group and a sarcopenia group. Sarcopenia was classified into two types: severe and nonsevere. The area, volume, and density of the erector spinae (ES) were measured using chest CT images, and the relevant ESP, including the erector spinae index (ESI), total erector spinae volume (TESV), erector spinae density (ESD), and erector spinae gauge (ESG) were calculated. The occurrence of adverse events was followed-up for 36 months. The diagnostic value and severity of US were determined using the receiver operating characteristic (ROC) curve. Survival curves diagnosed using CT were plotted and compared with the curve drawn using the gold standard. Cox regression analysis was used to identify independent risk factors associated with survival in US. RESULTS: With an area under the curve (AUC) of 0.840 and 0.739, the combined ESP has diagnostic value and the ability to assess the severity of US. There was no significant difference in the survival curve between the combined ESP for the diagnosis of US and the gold standard (P > 0.05). ESI is a standalone predictor of survival in patients with US. CONCLUSION: ESP measured by CT has diagnostic values for US and its severity, as well as being a predictive value for the prognosis of US.
Subject(s)
Sarcopenia , Tomography, X-Ray Computed , Uremia , Humans , Sarcopenia/diagnostic imaging , Sarcopenia/complications , Male , Female , Prognosis , Tomography, X-Ray Computed/methods , Middle Aged , Uremia/complications , Uremia/diagnostic imaging , Paraspinal Muscles/diagnostic imaging , Aged , Retrospective Studies , Severity of Illness IndexABSTRACT
1. Skeletal muscle is an important component of chicken carcass. In chickens, the number of muscle fibres is fixed during the embryonic period, and muscle development during the embryonic period determines the muscle development potential after hatching.2. Beijing-You (BY) and Cornish (CN) chickens show completely different growth rates and body types, and two breeds were used in this study to explore the role of lncRNAs in muscle development during different chicken embryonic periods. A systematic analysis of lncRNAs and mRNAs were conducted in the pectoral muscle tissues of BY and CN chickens at embryonic days 11 (ED11), 13 (ED13), 15 (ED15), 17 (ED17), and 1-day-old (D1) using RNA-seq. A total of 4,104 differentially expressed transcripts (DETs) were identified among the five stages, including 2,359 lncRNAs and 1,745 mRNAs.3. The number of DETs between the two breeds at ED17 (1,658 lncRNAs and 1,016 mRNAs) was much higher than the total number of DET at all the other stages (692 lncRNAs and 729 mRNAs), indicating that the two breeds show the largest difference in gene regulation at ED17.4. Correlation analysis was performed for all differentially expressed lncRNAs and mRNAs during the five periods. Forty-three, cis interaction pairs of lncRNA-mRNA related to chicken muscle development were predicted. The expression of four pairs was verified, and the results showed MSTRG.12395.2-FGFBP2 and MSTRG.18590.6-FMOD were significantly up-regulated in CN at ED11 compared to BY and might be important candidate genes for embryonic muscle development.
Subject(s)
Chickens , Gene Expression Profiling , Muscle Development , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Chickens/genetics , Chickens/growth & development , Muscle Development/genetics , Gene Expression Profiling/veterinary , Chick Embryo , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Expression Regulation, Developmental , Transcriptome , Pectoralis MusclesABSTRACT
BACKGROUND: Periodontitis is closely associated with chronic systemic diseases. Healthy lifestyle interventions have health-enhancing effects on chronic systemic disorders and periodontitis, but the extent to which healthy lifestyle combinations are associated with periodontitis is unclear. Therefore, this study aimed to investigate the association between periodontitis and different healthy lifestyle combinations. METHODS: 5611 participants were included from the National Health and Nutrition Examination Survey (NHANES, 2009-2014). Six healthy lifestyles factors were defined as fulfilling either: non-smoking, moderate drinking, moderate body mass index (BMI), physical activity, healthy sleep and appropriate total energy intake. Then, the adjusted logistic regression models were performed to identify the association between the periodontitis and the scoring system composed of six lifestyles (0-6 scale). Finally, different scenarios were dynamically and randomly combined to identify the optimal and personalized combination mode. RESULTS: Higher healthy lifestyle scores were significantly associated with lower periodontitis prevalence (p < 0.05). Four lifestyle factors (smoking, drinking, BMI, and sleep) significantly varied between the periodontitis and healthy groups (p < 0.05). Smoking was considered as a strong independent risk factor for periodontitis in both former and current smokers. Results further indicated that the combination of these four lifestyles played the most essential role in determining the magnitude of periodontitis occurrence (odds ratio [OR]: 0.33; 95% confidence interval [CI]: 0.21 to 0.50). In the total population, the majority of three lifestyle combinations outperformed the two combination models, whereas the two-combination of nonsmoking-drinking (OR: 0.39; 95% CI: 0.27 to 0.58) had relatively lower periodontitis prevalence than the three-combination of healthy drinking-BMI-sleep (OR: 0.42; 95% CI: 0.26 to 0.66). CONCLUSION: This cross-sectional study suggests that smoking, drinking, BMI, and sleep are significantly related with periodontitis and smoking is the principal risk factor related among them. This study provides various customized lifestyle combinations for periodontitis prevention.
Subject(s)
Periodontitis , Humans , Nutrition Surveys , Cross-Sectional Studies , Periodontitis/epidemiology , Risk Factors , Healthy Lifestyle , Chronic DiseaseABSTRACT
BACKGROUND: Primary Sjogren's syndrome (pSS) is a common autoimmune disorder that affects up to 0.3-3% of the global population. Ferroptosis has recently been identified to play a significant role in autoimmune diseases. However, the molecular mechanisms of ferroptosis in the initiation and progression of pSS remains unclear. MATERIAL AND METHODS: To investigate the molecular mechanisms underlying the occurrence and progression of pSS, we utilized a comprehensive approach by integrating data obtained from the Gene Expression Omnibus (GEO) database with data from the FerrDb database to identify the ferroptosis-related differentially expressed genes (DEGs). Furthermore, we implemented an innovative transcriptomic analysis method utilizing a computer-aided algorithm to establish a network between hub genes associated with ferroptosis and the immune microenvironment in pSS patients. RESULTS: Our results revealed significant differences in the gene expression profiles of pSS samples compared to normal tissues, with 1,830 significantly up-regulated genes and 1,310 significantly down-regulated genes. In addition, our results showed a significant increase in the proportions of B cells and CD4+ T cells in pSS samples compared to normal tissues. AND then, our analysis revealed that a combination of six ferroptosis-related genes, including TBK1, SLC1A4, PIK3CA, ENO3, EGR1, and ATG5, could serve as optimal markers for the diagnosis of pSS. The combined analysis of these six genes accurately diagnosed the occurrence of pSS. CONCLUSIONS: This study offers valuable insights into the pathogenesis of pSS and highlights the importance of targeting ferroptosis-related DEGs, which suggests a novel treatment strategy for pSS.
Subject(s)
Ferroptosis , Sjogren's Syndrome , Humans , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/genetics , Machine Learning , Algorithms , Databases, FactualABSTRACT
The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.
Subject(s)
Livedo Reticularis , Peripheral Nervous System Diseases , Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Cyanosis/complications , Hypesthesia/complications , Livedo Reticularis/complications , Pain , Retrospective StudiesABSTRACT
Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.
Subject(s)
Alternative Splicing , Brain Neoplasms , Cell Proliferation , Ferritins , Ferroptosis , Glioblastoma , Oxidoreductases , Serine-Arginine Splicing Factors , Humans , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Ferroptosis/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/metabolism , Prognosis , RNA, Small Interfering/genetics , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolismABSTRACT
We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic , Granulomatosis with Polyangiitis , Male , Humans , Aged , Granulomatosis with Polyangiitis/diagnosis , Biopsy , Cough , NecrosisABSTRACT
Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in Aspergillus infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in Aspergillus infections.
Subject(s)
Interferons , Humans , Aspergillus , Aspergillosis/immunology , Pulmonary Aspergillosis/immunology , Pulmonary Aspergillosis/drug therapyABSTRACT
Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.
Subject(s)
Nerve Sheath Neoplasms , Pleural Neoplasms , Humans , Male , Pleural Neoplasms/secondary , Pleural Neoplasms/pathology , Nerve Sheath Neoplasms/pathology , Nerve Sheath Neoplasms/secondary , Nerve Sheath Neoplasms/diagnosis , AdultABSTRACT
Objective: To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma. Methods: This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect. Results: Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.092, P=0.039),and had a positive predictive effect on the surgical method (ß=0.244,P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions: The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
Subject(s)
Bile Duct Neoplasms , Biomarkers, Tumor , Cholangiocarcinoma , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/blood , Cholangiocarcinoma/diagnosis , Male , Middle Aged , Female , Retrospective Studies , Prognosis , Aged , Biomarkers, Tumor/blood , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/blood , Bile Duct Neoplasms/diagnosis , Adult , Aged, 80 and over , Young Adult , Hepatectomy/methods , Preoperative PeriodABSTRACT
Objective: To investigate the early predictors of respiratory depression in patients with glufosinate poisoning, and provide reference for clinicians to make decisions. Methods: In March 2022, the clinical data of patients with glufosinate poisoning admitted to the intensive care unit of the Affiliated Xiangshan Hospital of Wenzhou Medical University from March 2018 to January 2022 were retrospectively analyzed. The patients were divided into respiratory depression group and non-respiratory depression group according to the occurrence of respiratory depression during hospitalization. The clinical data such as age, gender, past history, intake, initial treatment and laboratory examination were compared between the two groups. Multivariate logistic regression was used to analyze the predictors of respiratory depression in patients with glufosinate poisoning, and its predictive value was analyzed by receiver operating characteristic (ROC) curve. Results: A total of 34 patients with glufosinate poisoning were enrolled, including 13 patients in non-respiratory depression group and 21 patients in respiratory depression group. There were significant differences in intake, blood amylase and bicarbonate radical in arterial blood gas between the two groups (P<0.05). Respiratory depression occurred at 6.5-48.0 h after ingestion, with a median of 15.0 (9.5, 24.0) h. Multivariate logistic regression analysis showed that the intake of glufosinate (OR=1.440, 95%CI: 1.033-2.009, P=0.032) and bicarbonate radical in arterial blood gas (OR=0.199, 95%CI: 0.040-0.994, P=0.049) were predictors of respiratory depression in patients with glufosinate poisoning, and the area under the curve (AUC) of ROC curves were 0.936 and 0.842. The optimal cut-off values were 15.0 g (sensitivity=95.2%, specificity=76.9%) and 17.6 mmol/L (sensitivity=71.4%, specificity=84.6%), respectively. Conclusion: The intake of glufosinate and bicarbonate radical in arterial blood gas have good prediction effects on the occurrence of respiratory depression in patients with glufosinate poisoning.
Subject(s)
Aminobutyrates , Bicarbonates , Respiratory Insufficiency , Humans , Retrospective Studies , Prognosis , ROC CurveABSTRACT
Quantum technology has led to increasingly sophisticated and complex quantum devices. Assessing their reliability (quantum reliability) is an important issue. Although reliability theory for classical devices has been well developed in industry and technology, a suitable metric on quantum reliability and its loss has not been systematically investigated. Since reliability loss depends on the process, quantum fidelity does not always fully depict it. This study provides a metric of quantum reliability by shifting the focus from state distinguishing to trajectory distinguishing. In contrast to the conventional notion of classical reliability, which is evaluated using probabilistic measurements of binary logical variables, quantum reliability is grounded in the quantum probability amplitude or wave function. This research provides a universal framework for reliability theory encompassing both classical and quantum devices. It offers a new perspective on quantum engineering by elucidating how intensely the real quantum process that a device undergoes influences its performance.
ABSTRACT
BACKGROUND: Pure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves. Case presentation This report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations-namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium-in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations. CONCLUSION: Prominent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum's disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.
Subject(s)
Multiple Endocrine Neoplasia Type 2b , Humans , Multiple Endocrine Neoplasia Type 2b/diagnosis , Multiple Endocrine Neoplasia Type 2b/genetics , Eyelids , Face , Mutation , PhenotypeABSTRACT
1. As RIPK2 (receptor interacting serine/threonine kinase 2) has been shown to to alleviate excessive inflammatory responses, the following study conducted a systematic and in-depth analysis of the mRNA-seq and miRNA-seq data from chicken macrophages with/without over-expression of RIPK2 (oeRIPK2) combined with/without avian pathogenic E. coli (APEC) infection to identify the miRNA-mRNA interaction network and potential signalling pathways involved.2. A total of 9,201 differentially expressed (DE) mRNAs and 300 DE miRNA were identified in both oeRIPK2+APEC vs. APEC and oeRIPK2 vs. the wild-type (WT). Moreover, 4,269 instances of co-expression between miRNAs and mRNAs were seen involving 1,652 DE mRNAs and 164 DE miRNAs.3. Functional analysis of the DE mRNAs in the miRNA-mRNA interaction network showed that 223 biological processes and five KEGG pathways were significantly enriched in the two comparisons. In total, 128 pairs of miRNA-mRNA interactions were involved in the identified MAPK signalling pathway and focal adhesion immune related pathways.4. Significantly, these screened miRNAs (gga-miR-222b-5p and gga-miR-214) and their target genes were highly correlated with APEC infection and RIPK2. These recognised key genes, miRNA and the overall miRNA-mRNA regulatory network, enables better understanding of the molecular mechanism of host response to APEC infection, especially related to RIPK2.
Subject(s)
MicroRNAs , Transcriptome , Animals , Chickens/genetics , Chickens/metabolism , Escherichia coli/genetics , RNA, Messenger/genetics , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Objective: To summarize the clinical use of palbociclib and evaluate its efficacy and safety in hormone-receptor (HR)-positive advanced breast cancer patients. Methods: We retrospectively analyzed data from 66 HR-positive metastatic breast cancer patients treated with palbociclib and endocrine therapy at the Department of Oncology in the First Affiliated Hospital with Nanjing Medical University between 2018 and 2020. We evaluated the factors affecting the efficacy of palbociclib using Kaplan-Meier method and Log-rank test for survival analysis and Cox regressions for multivariate analysis. Nomogram model was built for predicting prognosis among HR-positive breast cancer patients who received palbociclib. Concordance index (C-index) and calibration curve were used for internal validation to assess the predictive ability and conformity of the model. Results: Of the 66 patients treated with palbociclib, 33.3%(22), 42.4%(28) and 24.2%(16) patients were treated without endocrine therapy, first-line endocrine therapy, second-line or above endocrine therapy after recurrence, respectively. 36.4%(24) patients had hepatic metastasis, 16.7% (11) patients were sensitive to previous endocrine therapy, 27.3%(18/66) patients had primary resistance to endocrine therapy, while 56.1% (37) patients had secondary resistance to endocrine therapy. The overall response rate was 14.3% (95% CI: 6.7%, 25.4%) and clinical benefit rate was 58.7% (95% CI: 45.6%, 71.0%). Better clinical outcomes were associated with non-hepatic metastasis (P=0.001), sensitive/secondary resistant to previous endocrine therapy (P=0.004), no or only one line of chemotherapy for metastatic breast cancer (P=0.004), recent pathological confirmation of immunohistochemical analysis (P=0.025). Hepatic metastasis (P=0.005) and primary resistance to endocrine therapy (P=0.016) were the independent risk factors of progression free survival. The C-index of predictive probability for the nomogram constructed from the patient clinical characteristics (whether liver metastasis, whether primary endocrine resistance, lines of chemotherapy after metastasis, lines of endocrine therapy, number of metastatic sites, and time to last immunohistochemistry) to predict the progression-free survival at 6 and 12 months for patients was 69.7% and 72.1%, respectively. The most common adverse events were hematologic toxicities. Conclusions: Our report indicates that palbociclib combined with endocrine therapy for HR-positive recurrent metastatic breast cancer is effective and safe; patients with hepatic metastases and primary resistance to endocrine therapy have worse prognoses and are independent risk factors for progression after palbociclib therapy. The constructed nomogram could help predict the survival and guide the use of palbociclib.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptor, ErbB-2/analysisABSTRACT
Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/chemically induced , Paclitaxel/adverse effects , Liposomes/therapeutic use , Retrospective Studies , Treatment Outcome , Trastuzumab/therapeutic use , Capecitabine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.
Subject(s)
Opsoclonus-Myoclonus Syndrome , Humans , Adult , Female , Opsoclonus-Myoclonus Syndrome/diagnosis , Opsoclonus-Myoclonus Syndrome/etiology , Immunomodulation , Vertigo/etiologyABSTRACT
Objective: To compare the outcomes between iliac crest and accessory navicular as different bone grafts in the Cotton osteotomy in the treatment of pediatric flexible flatfoot deformity. Methods: A retrospective cohort study. The clinical data of pediatric flexible flatfoot patients with symptomatic accessory navicular received operations from July 2018 to March 2022 in Beijing Tongren Hospital were retrospectively analyzed. All the patients were treated with Cotton osteotomy. According to the different sources of bone grafting in Cotton osteotomy, the patients were divided into iliac crest group and accessory navicular group. There were 12 patients (19 feet) in iliac crest group, including 9 males and 3 females with a median age M(Q1, Q3) of 11(11, 12) years and were followed-up for 36(6, 48) months. There were 9 patients (16 feet) in accessory navicular group, including 6 males and 3 females, with a median age M(Q1, Q3) of 11(11, 11) years and were followed-up for 12(6, 17) months. Radiographic evaluations were reviewed and compared between the two groups before surgical treatment and at final follow-up, included talo-1st metatarsal angle (T1MT), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA) in weight bearing anteroposterior view, and Meary angle, calcaneal Pitch angle, Kite angle, cuneiform articular angle (CAA) in weight bearing lateral view, and hindfoot alignment angle (HAA) in calcaneal long axial view. Functional scores included American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Maryland scores were recorded and compared before and after the operation. The complications were also recorded. Results: Total of 21 patients were successfully followed in this study. The radiographic measurements in the two groups, such as T1MT, TNCA, Meary angle, Pitch angle, Kite angle, CAA, HAA, were all significantly improved at the last follow-up when compared with those before the surgery (all P<0.05); and the AOFAS, VAS, Maryland scores in both groups were all improved after the surgery (all P<0.05). There was a significant difference in CAA alteration (∆CAA) after the operation between the two groups, the ∆CAA in iliac crest group and the accessory navicular group was 6.0°±2.6° and 4.3°±1.3°, respectively (P=0.017). There was no significant differences in the improvement of other radiographic measurements between the two groups (all P>0.05). All the patients had a successful bone union. Two patients had donor site pain in the iliac crest group and were treated conservatively. Conclusion: Compared with iliac crest bone graft, accessory navicular bone graft could achieve comparable outcomes in radiographic measurements and functional scores in the treatment of pediatric flexible flatfoot with accessory navicular pain.
Subject(s)
Flatfoot , Female , Male , Humans , Adolescent , Child , Flatfoot/surgery , Ilium , Retrospective Studies , Osteotomy , PainABSTRACT
To investigate the clinical and radiographic results of anterior tibial tendon (ATT) transfer combined with supramalleolar osteotomy in stage 3b of varus ankle osteoarthritis. Totally 13 patients with stage 3b of varus ankle osteoarthritis who received ATT transfer combined with supramalleolar osteotomy in Beijing Tongren Hospital from January 2018 to May 2021 were recruited. There were 6 males and 7 females with a mean age of (57.8±9.3) years. The overall evaluations included the preoperatively and postoperatively radiographic alignments, visual analog scale (VAS) score, and the American Orthopaedic Foot & Ankle Society (AOFAS) clinical ankle-hindfoot scale. The mean follow-up period was (33.5±13.4) months. The tibial articular surface (TAS), talar tilt (TT), and foot and ankle offset (FAO) changed from 83.3°±2.4° to 92.8°±1.7°, 12.3°±4.5° to 7.0°±4.7°, and -7.4%±2.8% to -0.7%±2.2% after the operation, respectively (all P<0.001). The AOFAS and VAS score improved significantly at the final follow-up when compared with those before the operation (both P<0.001). It indicated that ATT transfer after supramalleolar osteotomy can achieve good clinical and radiographic results in the treatment of varus ankle arthritis in Takakura stage 3b.