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The discovery of RNA silencing has revealed that non-protein-coding sequences (ncRNAs) can cover essential roles in regulatory networks and their malfunction may result in severe consequences on human health. These findings have prompted a general reassessment of the significance of RNA as a key player in cellular processes. This reassessment, however, will not be complete without a greater understanding of the distribution and function of the over 170 variants of the canonical ribonucleotides, which contribute to the breathtaking structural diversity of natural RNA. This review surveys the analytical approaches employed for the identification, characterization, and detection of RNA posttranscriptional modifications (rPTMs). The merits of analyzing individual units after exhaustive hydrolysis of the initial biopolymer are outlined together with those of identifying their position in the sequence of parent strands. Approaches based on next generation sequencing and mass spectrometry technologies are covered in depth to provide a comprehensive view of their respective merits. Deciphering the epitranscriptomic code will require not only mapping the location of rPTMs in the various classes of RNAs, but also assessing the variations of expression levels under different experimental conditions. The fact that no individual platform is currently capable of meeting all such demands implies that it will be essential to capitalize on complementary approaches to obtain the desired information. For this reason, the review strived to cover the broadest possible range of techniques to provide readers with the fundamental elements necessary to make informed choices and design the most effective possible strategy to accomplish the task at hand.
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Processamento Pós-Transcricional do RNA , RNA , Humanos , RNA/genética , Análise de Sequência de RNA/métodosRESUMO
AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.
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Tecido Adiposo , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Angiografia Coronária/métodos , Tecido Adiposo/diagnóstico por imagem , Idoso , Tecido Adiposo EpicárdicoRESUMO
AIMS: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. MATERIALS AND METHODS: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. RESULTS: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (ß = -11.755, P=0.001), LAA FV (ß = -17.364, P=0.004), LAA PEV (ß = -18.743, P<0.001), and LAA WMV (ß = -7.740, P=0.001) in multiple linear regression analysis. CONCLUSIONS: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.
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OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ã(L-AEFNIC) - ã(L-AEFC) (r= 0.419; p< 0.0001), ã(O-AEF40KeV) - ã(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.
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Neoplasias Pulmonares , Mediastinite , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Pessoa de Meia-Idade , Mediastinite/diagnóstico por imagem , Mediastinite/complicações , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/complicações , Idoso , Esclerose/diagnóstico por imagem , Esclerose/complicações , Adulto , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem , Broncoscopia/métodosRESUMO
Objective: To compare the efficacy of gasless robotic surgery through transaxillary approach and open surgery for papillary thyroid carcinoma (PTC). Methods: The data of patient undergoing robotic surgery through transaxillary approach and traditional open surgery for PTC at the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from November 2016 to June 2023 were retrospectively analyzed. A 1â¶1 propensity score matching (PSM) was performed to balance age, sex, extent of surgery, tumor size, capsule invasion, and multifocality. Surgical data, postoperative pathological data, complications, postoperative 2-month visual analog scale (VAS) scores for aesthetics, and follow-up data were compared between the two groups. Results: A total of 728 PTC patients were included. There were 339 patients in the robotic group, among which 262 were female (77.3%) and 77 were male (22.7%), with the age of [M (Q1, Q3)] 39 (32, 46) years and a body mass index (BMI) of 22.8 (20.7, 25.0) kg/m². Meanwhile, 389 patients were in the open group, among which 290 were female (74.6%) and 99 were male (25.4%), with the age of 47 (38, 55) years and a BMI of 23.2 (21.3, 25.5) kg/m2. Further analysis after PSM (there were 264 cases in both groups) showed that in the subtotal thyroidectomy and central neck dissection (LT+CCND) subgroup, the robotic group had longer operative time, higher blood loss, and greater drainage volume compared with the open group [100 (80, 130) min vs 60 (50, 80) min; 10 (10, 20) ml vs 10 (10, 20) ml; 103 (69, 145) ml vs 75 (57, 98) ml; all P<0.001], and the central lymph node metastasis rate was higher in the robotic group [45.6% (57/125) vs 31.8% (47/148), P=0.019]. In the total thyroidectomy and central neck dissection (TT+CCND) subgroup, the robotic group also had longer operative time, higher blood loss, and greater drainage volume compared with the open group [150 (110, 180) min vs 85 (75, 100) min; 20 (10, 20) ml vs 10 (10, 20) ml; 155 (107, 206) ml vs 90 (70, 120) ml; all P<0.001]. The incidence of chest skin numbness at 3 months postoperatively was higher in the robotic group compared with the open group (12.9% vs 0, P<0.001), while there were no statistically significant differences in other postoperative complications (all P>0.05). The VAS score at 2 months postoperatively was higher in the robotic group compared with the open group [9 (9, 9) vs 8 (7, 9), P<0.001]. Three cases of contralateral lobe recurrence occurred in the open group, while there were no case of recurrence in the robotic group. The 5-year overall survival rate was 100.0% in both the robotic and open groups, and there was no statistically significant difference in the 5-year disease-free survival rate between the robotic and open groups (100.0% vs 98.6%, P=0.068). Conclusion: Gasless robotic surgery through transaxillary approach for total thyroidectomy or lobectomy in the treatment of PTC is safe, feasible, and effective, with good cosmetic outcomes and comparable efficacy to traditional surgery.
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Axila , Procedimentos Cirúrgicos Robóticos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Feminino , Câncer Papilífero da Tireoide/cirurgia , Adulto , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Pessoa de Meia-Idade , Tireoidectomia/métodos , Resultado do Tratamento , Duração da Cirurgia , Pontuação de PropensãoRESUMO
AIM: To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression. MATERIALS AND METHODS: A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods. RESULTS: Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively. CONCLUSION: MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Queratina-19/análise , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Estudos RetrospectivosRESUMO
AIM: To investigate the relationship between different plaque characteristics and pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation values for plaques and periplaques. MATERIALS AND METHODS: The data from 188 eligible patients with stable coronary heart disease (280 lesions) who underwent coronary CT angiography between March 2021 and November 2021 were collected retrospectively. All PCAT CT attenuation values of plaques and periplaques (the area within 5 and 10 mm proximal and distal to the plaque) were calculated, and multiple linear regression was used to assess their correlation with different plaque characteristics. RESULTS: PCAT CT attenuation of plaques and periplaques was higher in non-calcified plaques (-73.38 ± 10.41 HU, -76.77 ± 10.86 HU, 79.33 ± 11.13 HU, -75.67 ± 11.24 HU, -78.63 ± 12.09 HU) and mixed plaques (-76.83 ± 8.11 HU, -79 [-85, -68.5] HU, -78.55 ± 11 HU, -78.76 ± 9.9 HU, -78.79 ± 11.06 HU) than in calcified plaques (-86.96 ± 10 HU, -84 [-92, -76] HU, -84.14 ± 11.08 HU, -84.91 ± 11.41 HU, -84.59 ± 11.69 HU; all p<0.05) and higher in distal segment plaques than in proximal segment plaques (all p<0.05). Plaque PCAT CT attenuation was lower in plaques with minimal stenosis than in plaques with mild or moderate stenosis (p<0.05). The significant determinants of PCAT CT attenuation values of plaques and periplaques were non-calcified plaques, mixed plaques, and plaques located in the distal segment (all p<0.05). CONCLUSIONS: PCAT CT attenuation values in both plaques and periplaques were related to plaque type and location.
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Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Doença da Artéria Coronariana/patologia , Angiografia Coronária/métodos , Estudos Retrospectivos , Constrição Patológica , Placa Aterosclerótica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos , Tecido Adiposo/diagnóstico por imagem , Vasos Coronários/patologiaRESUMO
AIM: To develop a deep-learning model to help general dental practitioners diagnose periodontitis accurately and at an early stage. MATERIALS AND METHODS: First, the panoramic radiographs (PARs) from the Second Affiliated Hospital of Nanchang University were input into the convolutional neural network (CNN) architecture to establish the PAR-CNN model for healthy controls and periodontitis patients. Then, the PARs from the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were included in the second testing set to validate the effectiveness of the model with data from two centres. Heat maps were produced using a gradient-weighted class activation mapping method to visualise the regions of interest of the model. The accuracy and time required to read the PARs were compared between the model, periodontal experts, and general dental practitioners. Areas under the receiver operating characteristic curve (AUCs) were used to evaluate the performance of the model. RESULTS: The AUC of the PAR-CNN model was 0.843, and the AUC of the second test set was 0.793. The heat map showed that the regions of interest predicted by the model were periodontitis bone lesions. The accuracy of the model, periodontal experts, and general dental practitioners was 0.800, 0.813, and 0.693, respectively. The time required to read each PAR by periodontal experts (6.042 ± 1.148 seconds) and general dental practitioners (13.105 ± 3.153 seconds), which was significantly longer than the time required by the model (0.027 ± 0.002 seconds). CONCLUSION: The ability of the CNN model to diagnose periodontitis approached the level of periodontal experts. Deep-learning methods can assist general dental practitioners to diagnose periodontitis quickly and accurately.
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Aprendizado Profundo , Humanos , Estudos Retrospectivos , Odontólogos , Papel Profissional , Redes Neurais de ComputaçãoRESUMO
PURPOSE: To explore the prevalence of nocturnal intermittent hypoxemia (NIH) in a tertiary hospital geriatric department and the relationship between NIH and mild cognitive impairment (MCI) in older adults, and to examine the role of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. METHODS: Older adults aged ≥ 60 were enrolled. NIH and cognitive assessments were conducted. BDNF concentrations and BDNF Val66Met polymorphism were detected for a preliminary exploration of the possible mechanism of the process. RESULTS: Of 325 older adults enrolled, 157 (48%) had NIH and were further divided into mild, moderate, and severe NIH groups according to their oxygen desaturation of ≥ 4% per hour of sleep (ODI4). MCI detection rate in the four groups gradually increased, and the differences were statistically significant (chi-square = 4.457, P = 0.035). ODI4 was negatively correlated with MoCA score in all participants (r = - 0.115, P = 0.039) and patients with NIH (r = - 0.199, P = 0.012). After adjusting for sex, age, and cardiovascular risk factors, NIH and MCI remained independently associated (OR = 3.13, 95% CI 1.03-9.53, P = 0.045). BDNF levels were positively correlated with MoCA score (r = 0.169, P = 0.028) and negatively correlated with nocturnal average oxygen saturation in patients with NIH (r = - 0.288, P = 0.008). Older adults with different BDNF Val66Met genotypes did not show significant differences in MCI rate and BDNF levels (P > 0.05). CONCLUSION: The older adults with NIH have a higher MCI detection rate. BDNF levels may be a potential biomarker for cognitive dysfunction in patients with NIH.
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Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Idoso , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Genótipo , Hospitais , Hipóxia/genéticaRESUMO
OBJECTIVES: This study aimed to project future temperature-associated mortality risk and additional deaths among Taiwan's elderly (aged >65 years) population. STUDY DESIGN: This study investigated retrospective temperature-mortality risk associations and future mortality projections. METHODS: A distributed lag non-linear model and random effect meta-analyses were employed to assess the risk of daily temperature-associated deaths in all-cause, circulatory, and respiratory diseases. Using the statistical downscaling temperature projections of the Representative Concentration Pathways (RCPs; i.e. RCP2.6, RCP6.0 and RCP8.5), future risk of mortalities were projected among the elderly for 2030-2039, 2060-2069 and 2090-2099, with a 30%, 40% and 50% expected increase in elderly population proportions, respectively. RESULTS: The baseline analysis from 2005 to 2018 identified that Taiwan's population is more vulnerable to cold effects than heat, with the highest cold-related mortality risk being attributed to circulatory diseases, followed by all-cause and respiratory diseases. However, future projections suggest a declining trend in cold-related mortalities and a significant rise in heat-related mortalities under different RCP scenarios. Heat-attributable mortalities under the RCP8.5 scenario by 2090-2099 would account for almost 170,360, 36,557 and 29,386 additional annual deaths among the elderly due to all-cause, circulatory and respiratory diseases, respectively. Heat-attributable all-cause mortalities among the elderly would increase by 3%, 11% and 30% under RCP2.6, RCP6.0 and RCP8.5, respectively, by 2090-2099. CONCLUSIONS: The findings of this study provide predictions on future temperature-related mortality among the elderly in a developed, ageing society with a hot and humid climate. The results from this study can guide public health interventions and policies for climate change and ageing society-associated health risks.
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Temperatura Alta , Doenças Respiratórias , Idoso , Humanos , Temperatura , Estudos Retrospectivos , Envelhecimento , Mudança Climática , MortalidadeRESUMO
Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
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Esofagite , Lesão Pulmonar , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Lesões por Radiação , Radioterapia de Intensidade Modulada , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Dosagem Radioterapêutica , Lesões por Radiação/etiologia , Lesões por Radiação/epidemiologia , Esofagite/etiologia , Esofagite/epidemiologia , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/complicaçõesRESUMO
To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of uterine carcinosarcoma (UCS), and to explore the gene mutation characteristics and tumor mutation burden (TMB) of UCS. The clinical imaging, pathomorphological data and immunohistochemical expression of 4 cases of UCS, which were archived in the Department of Pathology of the Second Affiliated Hospital of Soochow University from January 2021 to May 2022 were retrospectively analyzed. All exon groups of 4 cases of UCS were sequenced. All the 4 patients were female, aged 47-81 years. The maximum diameter of the tumor was 4.0-13.0 cm, and the boundary was unclear. Microscopically, the tumor was composed of malignant epithelium and sarcoma. Immunohistochemistry showed that the epithelial components of 4 patients expressed broad-spectrum cytokeratin (AE1/E3), the sarcoma components expressed Vimentin, PAX8, ER, PR were expressed to varying degrees, and Ki-67 positive index was high (60%-90%). There were 3 p53 missense mutations, 1 nonsense mutation, 4 MLH1, PMS2, MSH2, MSH6 were positive and PD-L1 was negative. The sequencing results of the whole exon group of 4 UCS patients showed that TP53, BCL9L, BRD4, CLTCLI, PSMD1I, PLEC genes showed a high mutation ratio, which was 3/4, 2/4, 2/4, 2/4, 2/4, 2/4, respectively. TMB analysis showed that the TMB of 4 cases of UCS was<5 mut/Mb. UCS is a rare and highly malignant endometrial tumor. The sequencing results of the whole exon group suggested that TP53, BCL9L, BRD4 and other genes had high mutation rates, suggesting that the occurrence and development of UCS may be closely related to Wnt signaling pathway. Molecular typing indicated that 3 cases of UCS were of high copy number type/p53 mutation type, and 1 case had POLD1 mutation. Microsatellite stability, low PD-L1 expression and TMB results suggested that UCS patients have no obvious advantage in immunotherapy.
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Carcinossarcoma , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Masculino , Proteína Supressora de Tumor p53/genética , Antígeno B7-H1/genética , Estudos Retrospectivos , Proteínas Nucleares/genética , Carcinossarcoma/genética , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/uso terapêutico , Neoplasias Uterinas/genética , Mutação , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genéticaRESUMO
This study observed the expression of ProEXC protein and PRMT5 protein in cervical adenocarcinoma and adjacent tissues, exploring the relationship between the expression of ProEXC and PRMT5 and the auxiliary diagnosis of cervical adenocarcinoma, as well as the clinical pathological parameters. A total of 88 specimens diagnosed with cervical adenocarcinoma from the Second Affiliated Hospital of Soochow University between 2015 and 2020 were collected. Immunohistochemistry was employed to detect the expression of ProEXC and PRMT5 in cervical adenocarcinoma and adjacent tissues, and statistical analysis was conducted. The Cancer Genome Atlas (TCGA) database was utilized to analyze the correlation between the prognosis of cervical adenocarcinoma patients and the expression of ProEXC and PRMT5, as well as their related gene pathways. The GSE39293 dataset from the Gene Expression Omnibus (GEO) was selected to compare the expression levels of ProEXC and PRMT5 in cervical adenocarcinoma cell lines (HELA) before and after antiviral drug treatment.In cervical adenocarcinoma tissues, the expression of ProEXC protein (95.5% vs 4.6%, P<0.001) and PRMT5 protein (81.8% vs 26.1%, P<0.001) was significantly higher than in surrounding adjacent tissues. Their expression was correlated with the tumor's T stage, lymph node metastasis, and human papillomavirus (HPV) infection (P<0.05). TCGA database analysis showed that patients with high expression of MCM2 in PRMT5 and ProEXC had a lower overall survival rate (P<0.05), while the expression of TOP2A was not significantly correlated with survival. In the GSE39293 dataset, the expression of MCM2 (9.34 vs 9.68, P<0.001) and PRMT5 (8.16 vs 8.26, P=0.087) in cells decreased after treatment with cidofovir, while TOP2A (8.54 vs 8.42, P=0.056) expression did not change significantly. In the drug-resistant group, the expression of PRMT5 (8.42 vs 8.16, P=0.002) and MCM2 (9.51 vs 9.34, P=0.029) increased, while TOP2A (8.06 vs 8.54, P<0.001) expression decreased. Gene set enrichment analysis (GSEA) suggested that high expression of ProEXC mainly affected the cell cycle pathway, while high expression of PRMT5 mainly affected the RNA splicing pathway.This study found that ProEXC protein and PRMT5 protein were highly expressed in cervical adenocarcinoma tissues, and the high-expression group had a poorer prognosis, showing a certain correlation with the clinical and pathological characteristics of cervical adenocarcinoma. This may be related to their influence on the cell cycle and RNA synthesis pathways, suggesting their potential significant roles in the progression of cervical adenocarcinoma.
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Adenocarcinoma , Neoplasias do Colo do Útero , Feminino , Humanos , Relevância Clínica , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Prognóstico , Proteína-Arginina N-MetiltransferasesRESUMO
In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).
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Vacinas contra Hepatite B , Hepatite B , Criança , Humanos , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , VacinaçãoRESUMO
Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.
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Síndrome de Alagille , Atresia Biliar , Colestase , Citrulinemia , Simportadores , Humanos , Recém-Nascido , Criança , Ácidos e Sais Biliares , Diagnóstico Diferencial , Ácido Taurocólico , Ácido Glicodesoxicólico , Ácido Litocólico , PeptídeosRESUMO
Objective: To analysis the main types and prevalences of complications among pneumoconiosis patients, and to provide scientific basis for the prevention and treatment of pneumoconiosis. Methods: In January 2023, literatures on pneumoconiosis complications published before December 31, 2022 in China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Science & Technology Journal Database (VIP), PubMed and Web of Science were systematically searched. Literatures were selected according to inclusion and exclusion criteria, and relevant data were extracted. Quality assessment tool was used to evaluate the quality of the articles for this study. The combined prevalence of complications among pneumoconiosis patients was calculated by R 4.1.1 software. Subgroup analysis was carried out to explore the origin of heterogeneity. Results: Sixty-four eligible articles were selected from 2276 literatures related to pneumoconiosis and its complications. The combined prevalence of complications among pneumoconiosis patients was 21.1% (95% CI: 16.0%-26.3%, I(2)=99.9%). The combined prevalence of chronic obstructive pulmonary disease (COPD) was 26.4% (95%CI: 17.3%-35.6%, I(2)=97.1%), which was the highest among different types of complications among pneumoconiosis patients. Subgroup analyses revealed that the combined prevalence of tuberculosis among pneumoconiosis stage â , â ¡and â ¢ were 13.8% (95%CI: 10.5%-17.2%, I(2)=99.6%), 18.4% (95% CI: 14.9%-22.0%, I(2)=99.3%) and 37.3% (95% CI: 30.7%-44.0%, I(2)=99.1%), respectively, showing a corresponding increasing tendency (P<0.05). The combined prevalence of tuberculosis among coal worker's pneumoconiosis patients was 12.9% (95% CI: 6.4%-19.3%, I(2)=97.9%), while the combined prevalence of tuberculosis among silicosis patients was 13.9% (95%CI: 10.0%-17.8%, I(2)=96.9%) . Conclusion: The prevalence of pneumoconiosis patients combined with different types of complications is high, and its prevalence increases with the severity of pneumoconiosis.
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Antracose , Pneumoconiose , Silicose , Tuberculose , Humanos , Prevalência , Pneumoconiose/epidemiologiaRESUMO
Objective: To explore the influence and significance of respiratory filter on the judgment of pulmonary function and the conclusion of occupational health examination in occupational health examination. Methods: From August to November 2020, 252 occupational health examinees were randomly selected as the research objects, and the lung function was examined with the respiratory filter bite and the straight cylinder bite without filter, respectively. The lung function examination indexes and the qualification rate of lung function examination were analyzed and compared between the two groups, and the diagnostic criteria of lung function examination was corrected. Results: 252 subjects were 36 (30, 42) years old. The qualified rate of lung function examination with respiratory filter bite (28.17%, 71/252) was lower than that with straight cylinder bite (34.92%, 88/252) , the difference was statistically significant (P<0.05) . The percentage of forced vital capacity in normal predicted value (FVC%) , percentage of forced expiratory volume in the first second in normal predicted value (FEV(1)%) , and percentage of forced expiratory volume in the first second in forced vital capacity (FEV(1)/FVC%) of subjects using respiratory filter bite were lower than those using the straight cylinder bite (P<0.05) . The corrected diagnostic criteria of pulmonary function were FVC%>78%, FEV(1)%>77%, FEV(1)/FVC%>68%. There was no significant difference between the qualified rate of the respiratory filter bite lung function test calculated according to the corrected diagnostic criteria (35.71%, 90/252) and the qualified rate of the straight cylinder bite lung function test calculated according to the original diagnostic criteria (34.92%, 88/252) (P>0.05) . Conclusion: In occupational health examination, the use of respiratory filter may affect the results of pulmonary function examination. The diagnostic criteria of pulmonary function can be corrected according to different filtering effects to ensure the accuracy of the conclusions of occupational health examination.
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Saúde Ocupacional , Humanos , Adulto , Pulmão , Capacidade Vital , Volume Expiratório Forçado , Testes de Função Respiratória/métodosRESUMO
BACKGROUND: miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. METHODS: RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). RESULTS: miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. CONCLUSIONS: A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.
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MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Ciclo Celular , Dano ao DNA , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genéticaRESUMO
We show theoretically the presence of an optical field polarization rotation blocking mechanism in single-probe-based magnetic field sensing schemes, revealing the root cause for extremely small nonlinear magneto-optical rotation (NMOR) signal in single-probe-based atomic magnetometers. We present a colliding-probe atomic magnetometer theory, analytically describing the principle of the first nonlinear-optical atomic magnetometer. This new atomic magnetometry technique breaks the NMOR blockade in single-probe atomic magnetometers, enabling an energy circulation that results in larger than 20-dB enhancement in NMOR signal as well as better than 6-dB improvement of magnetic field detection sensitivity. Remarkably, all experimental observations reported to date can be qualitatively well-explained using this colliding-probe atomic magnetometry theory without numerical computations. This colliding-probe atomic magnetometry technique may have broad applications in scientific and technological fields ranging from micro-Tesla magnetic resonance imaging to cosmic particle detection.
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OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.