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AIM: To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. MATERIALS AND METHODS: Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1native, T2native, and PDnative) and after (T1post, T2post, and PDpost) contrast agent injection. Student's t-test or the Mann-Whitney U-test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. RESULTS: The mean T1native, T2native, and T1post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p<0.05). The T1post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p<0.05). The combined T1native, T2native, and T1post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. CONCLUSIONS: Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs.
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Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Curva ROC , Edema/diagnóstico por imagem , PrótonsRESUMO
AIMS: Mounting evidence has shown that caveolin-1 plays a pathological role in the progression of albuminuria. Our study aimed to provide clinical evidence showing whether circulating caveolin-1 levels were associated with microalbuminuria (MAU) in women with overt diabetes mellitus in pregnancy (ODMIP). METHODS: A total of 150 pregnant women were enrolled in different groups, including 40 women with ODMIP and MAU (ODMIP + MAU), 40 women with ODMIP, and 70 women without ODMIP (Non-ODMIP). Plasma caveolin-1 levels were determined by ELISA. The presence of caveolin-1 in the human umbilical vein vascular wall was evaluated by immunohistochemical and western blot analysis, respectively. Albumin transcytosis across endothelial cells was measured using an established nonradioactive in vitro approach. RESULTS: Significantly increased levels of plasma caveolin-1 were detected in ODMIP + MAU women. The Pearson's correlation analysis revealed a positive correlation between plasma caveolin-1 levels and Hemoglobin A1c (HbA1c %) as well as with MAU in the ODMIP + MAU group. Simultaneously, experimental knockdown or overexpression of caveolin-1 significantly decreased or increased the level of albumin transcytosis across both human and mouse glomerular endothelial cells (GECs), respectively. CONCLUSIONS: Our data showed a positive association between plasma caveolin-1 levels and microalbuminuria in ODMIP + MAU.
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Diabetes Mellitus , Gravidez em Diabéticas , Gravidez , Humanos , Feminino , Animais , Camundongos , Albuminúria/complicações , Caveolina 1 , Células Endoteliais , Albuminas , Fatores de RiscoRESUMO
PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.
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PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.
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Acute Respiratory Distress Syndrome (ARDS) is distinguished by hypoxemia, contributing to heightened morbidity, elevated mortality rates, and substantial healthcare expenses, thereby imposing a significant burden on patients and society. Presently, effective treatments for ARDS are lacking, emphasizing the pivotal role of early diagnosis and timely intervention in its successful management. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, P/F) has traditionally served as a crucial metric for assessing patient hypoxemia and disease severity. While relatively accurate, its reliance on advanced technical expertise and specific medical equipment conditions constrains its implementation in areas with underdeveloped medical standards, resulting in missed diagnoses and treatments for ARDS patients. Conversely, the Pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2, S/F) has garnered increasing attention owing to its straightforward, non-invasive, and sustainable monitoring attributes. This article seeks to meticulously compare the correlation, accuracy, and clinical feasibility of S/F with P/F in ARDS diagnosis, so as to propose diagnostic indicators for more quickly and accurately assessing the oxygenation status of ARDS patients.
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Oxigênio , Síndrome do Desconforto Respiratório , Humanos , Pressão Parcial , Oximetria/métodos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , HipóxiaRESUMO
Objective: To anlysis the efficacy and safety of cut-umbilical cord milking (C-UCM) compared with immediate cord clamping in preventing anemia and iron deficiency among term cesarean-delivered newborns. Methods: A total of 485 pregnant women planning to deliver by cesarean section were recruited in this randomized controlled trial in Hunan Maternal and Child Health Hospital and Liuyang Maternal and Child Health Care Hospital from July 2016 to April 2019. A block randomization was conducted to evenly allocate them to the controlled group and the C-UCM group. In the controlled group, the cord was clamped within 30 seconds as routine. In the C-UCM group, the cord was first clamped at 25 cm from the newborn's navel, and then the blood in the cord was gently squeezed into the newborn's body until the cord became white and shriveled. The cord was clamped twice at 2-3 cm from the newborn's navel subsequently. Neonatal jaundice, hyperbilirubinemia and polycythemia were monitored before discharge. After the newborns discharged, their hemoglobin, red blood cell count, hematocrit (at the age of 1, 6 and 12 months) and serum ferritin (at the age of 6 and 12 months) were followed up; body length and weight were measured; and information about their feeding and iron supplementation were collected (at the age of 1, 6, 12 and 18 months). The two groups were compared by t test, Mann-Whitney U test, χ² test, or Fisher exact probability method. The hospital was set as a random item, and the mixed effects regression model was used to evaluate the effect of C-UCM on relevant indicators of cesarean-delivered newborns. Results: There were 244 women in the C-UCM group with an average age of (31.9±4.4) years, and 241 in the control group with an average age of (31.8±4.2) years (P>0.05). There was no statistically significant difference between the C-UCM group and the control group at 1, 6 and 12 months of age in hemoglobin [(123.6±14.5) vs (122.2±14.5) g/L, (115.3±9.4) vs (114.1±8.5) g/L, (115.6±9.6) vs (116.1±12.6) g/L] or anemia incidence rate [15.2% (17/112) vs 18.4% (19/103), 22.7% (34/150) vs 26.8% (44/164), 22.3% (25/112) vs 19.5% (22/113)] (all P>0.05). There was no statistically significant difference between the two groups at 6 and 12 months of age in serum ferritin [M (Q1, Q3), 39.9 (24.9, 61.8) vs 43.6 (25.2, 100.9) µg/L, 40.3 (25.4, 259.2) vs 40.3 (26.4, 167.6) µg/L)] or iron deficiency incidence rate [6.1% (5/82) vs 4.2% (3/72), 6.7% (5/75) vs 3.8% (3/80)] (all P>0.05). There were also no significant difference between the two groups in other indicators, such as the Z-score of weight-for-length, the incidence of neonatal jaundice, and the incidence of neonatal hyperbilirubinemia (all P>0.05). After adjusting for the relevant covariates, there were still no significant effects of C-UCM on these outcomes above. Conclusions: Compared to immediate cord clamping, the intervention of gently squeezing 25 cm of the cord does not significantly reduce the risk of anemia or iron deficiency in term cesarean-delivered newborns, nor does it have a significant impact on infant growth and development. Yet this intervention does not increase the risk of jaundice or hyperbilirubinemia in newborns as well.
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Anemia Ferropriva , Cesárea , Cordão Umbilical , Humanos , Feminino , Recém-Nascido , Gravidez , Anemia Ferropriva/prevenção & controle , Adulto , Sangue FetalRESUMO
Public health and social measures (PHSMs) are one of the most important measures in the prevention and control of COVID-19 and have also been effective in suppressing the spread of influenza viruses, but their effectiveness has not been fully investigated. This study aimed to review the progress of research on the impact of PHSMs on influenza during the COVID-19 pandemic based on the latest evidence of the effectiveness of various PHSMs in controlling transmission of influenza viruses, to provide scientific evidence for optimizing influenza prevention and control strategies.
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COVID-19 , Influenza Humana , Pandemias , Saúde Pública , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controleRESUMO
Objective: To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. Methods: A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined. Results: Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion (P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions: MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Inibidor p16 de Quinase Dependente de Ciclina , Homozigoto , Purina-Núcleosídeo Fosforilase , Humanos , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Astrocitoma/genética , Astrocitoma/metabolismo , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Deleção de Genes , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Mutação , Masculino , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Feminino , Adulto , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
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Antituberculosos , Nitroimidazóis , Oxazóis , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Masculino , Feminino , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Estudos Prospectivos , Rifampina/efeitos adversos , Pessoa de Meia-Idade , Oxazóis/efeitos adversos , Oxazóis/uso terapêutico , Oxazóis/administração & dosagem , Antituberculosos/efeitos adversos , Tuberculose Pulmonar/tratamento farmacológico , Nitroimidazóis/efeitos adversos , Nitroimidazóis/uso terapêutico , Nitroimidazóis/administração & dosagem , Idoso , China , Adulto Jovem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologiaRESUMO
In this paper, the security strength of an enhanced cryptosystem based on interference and the phase-retrieval technique is evaluated. The security strength of the optical cryptosystem was improved through the phase-retrieval technique used to generate a phase-only mask (POM) as the ciphertext. Due to the complex mathematical model of the phase-retrieval technique, it seems that a silhouette problem existing in the conventional interference-based scheme was removed. However, we noted that the random phase mask (RPM) regarded as the only private key was fixed in the encryption path, which is not related to the plaintext and makes it possible to be recovered using a known-plaintext attack (KPA). Moreover, we also found that the RPM has high key sensitivity, and it should be recovered precisely to retrieve information of plaintexts during the attack. Thus, a hybrid KPA where three pairs of known plaintexts and their ciphertexts are regarded as the amplitude and phase constraints to obtain the precise estimation of the RPM is proposed. Then, with the help of the estimated private key, information of the original plaintexts encoded using the cryptosystem under study could be retrieved from an arbitrarily given ciphertext without any knowledge of the private key. Our cryptoanalysis shows that the cryptosystem based on interference and the phase-retrieval technique is vulnerable to the proposed attack, and there is a security leak in it. Numerical simulations have been carried out to demonstrate the performance of our proposed attack.
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In this paper, the security strength of a double-image cryptosystem using spatial encoding and phase-truncation Fourier transforms (PTFTs) is evaluated. Unlike the conventional PTFT-based cryptosystem, where two random phase masks (RPMs) are used as public keys to provide enough phase constrains in the estimation, in the improved cryptosystem, the RPM generated by a random amplitude mask (RAM) is treated as an unknown parameter. Due to this fixed RAM, the number of constraints in the estimation decreases to achieve high robustness against potential iterative attacks. Moreover, instead of two phase-only masks (POMs), here the two POMs and the RAM are utilized as the private keys in the improved cryptosystem; thus, the key space of the double-image cryptosystem has been enlarged. However, we noticed that the RAM used to encode plaintexts spatially and to generate the phase encryption key is independent of the plaintexts. This could be recovered by a known pair of plaintexts and the ciphertext. Once the information of the RAM is retrieved, the phase key RPM can also be produced making the cryptosystem vulnerable. Based on this finding, new hybrid algorithms, including a known-plaintext attack and a known key attack are proposed to crack the enhanced PTFT-based cryptosystem. The information of the plaintexts can be retrieved from one POM using the proposed algorithms without any knowledge of another POM and the corresponding ciphertext. Numerical simulations have been carried out to validate the information disclosure problem still exists in the double-image cryptosystem based on spatial encoding and PTFTs.
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Objective: To investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST). Method: A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results: A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1â¶100, 1â¶320, and 1â¶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender (OR=1.980, 95%CI 1.206-3.277), older age (OR=1.017, 95%CI 1.003-1.032), and presence of PNH clone (OR=1.875, 95%CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females (OR=1.24, 95%CI 1.02-1.51), severe AA (OR=1.26, 95%CI 1.07-1.47), and age≥40 years (OR=1.26, 95%CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions: Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.
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Anemia Aplástica , Autoanticorpos , Humanos , Feminino , Masculino , Adulto , Anemia Aplástica/tratamento farmacológico , Estudos de Casos e Controles , Estudos Retrospectivos , Terapia de ImunossupressãoRESUMO
OBJECTIVE: To compare the consistency of programmed cell death 1-ligand 1 (PD-L1, clone E1L3N, 22C3, SP263) in different immunohistochemical staining methods. METHODS: The first step was to select the optimal process: The PD-L1(clone E1L3N) antibody recommended process, self-built process â , self-built process â¡ and self-built process ⢠were used to perform immunohistochemical staining in 5 cases of tonsil tissue. The quality of all slides was scored by expert pathologists (0-6 points). The process with the highest score was selected. The second step was to compare the consistency between the optimal procedure and the two standard procedures. Thirty-two cases of lung non-small cell carcinoma diagnosed by pathology in Peking University First Hospital in the past two years were randomly selected. The 32 cases were stained in parallel with the SP263 and 22C3 standard procedures, and all stained slides were scored by specialized pathologists for tumor proportion score (TPS). The scoring results were grouped according to < 1%, ≥1% to < 10%, ≥10% to < 50%, and ≥50%. The consistency of PD-L1 detection antibody clone E1L3N and 22C3, E1L3N and SP263 staining results was analyzed. RESULTS: Tonsil stained slides scores (0-6 points) were as follows: The recommended protocol was 5, 5, 5, 5 and 5. The self-built process â was 5, 6, 6, 5 and 6. The self-built process â¡ was 4, 4, 4, 4 and 4.The self-built process ⢠was 3, 3, 3, 3 and 3. The self-built process â was the best with the highest score. The TPSs of 32 non small cell lung carcinoma (NSCLC) cases were as follows: Of self-built process â , 6 cases were lower than 1%, 5 cases were from 1% to 10%, 10 cases were from 10% to 50%, and 11 cases were higher than 50%; of 22C3 standard procedure, 5 cases were lower than 1%, 3 cases were from 1% to 10%, 13 cases were from 10% to 50%, 11 cases were higher than 50%; of SP263 standard procedure, 7 cases were lower than 1%, 4 cases were from 1% to 10%, 11 cases were from 10% to 50%, 10 cases were higher than 50%. The results of the consistency test were as follows: The κ value for self-built process â and 22C3 standard procedure was 0.736 (P < 0.001), the agreement was good; the κ value for self-built process â and SP263 standard procedure was 0.914 (P < 0.001), the agreement was very good. CONCLUSION: The immunostaining using PD-L1(E1L3N) with validated self-built staining protocol â by Ventana Benchmark GX platform can obtain high quality of slides, and the TPSs based on these slides are in good agreement with 22C3 and SP263 standard procedures.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Imuno-Histoquímica , Antígeno B7-H1/metabolismo , Ligantes , Anticorpos , Coloração e Rotulagem , ApoptoseRESUMO
We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (â ¢A). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Torácicas , Humanos , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Neoplasias Pulmonares/genética , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/genética , Neoplasias Torácicas/patologia , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
Placental transmogrification of the lung (PTL) is a very rare benign lung lesion. There are only about 40 cases reported in the literature. The imaging and histological features of PTL cases in the publication are various, most of which are cystic and a few of which are solid. Being extremely rare, the solid PTL is unknown to major pathologists and surgeons. We reported a case of solid PTL in the anterior mediastinum. The patient was a 52-year-old male with no history of smoking and without symptoms. During physical examination, chest CT revealed a circular low-density lesion with a maximum diameter of 2.9 cm beside the spine in the posterior basal segment of the left lower lobe of the lung. The wedge resection was performed by video-assisted thoracoscopy. Grossly, a round nodule was located underneath the visceral pleura. It was about 3.0 cm×3.0 cm×1.6 cm and the cut surface was grey-red, soft and spongy. Microscopically, the nodule was constituted of papillare, which resembled placental villi at low magnification. The axis of papillae was edema, in which some mild round cells with clear cytoplasm and CD10 positive staining aggregated and transitioned to immature adipocytes and amorphous pink materials deposited with a few of inflammatory cells infiltration. The surface of papillae was covered with disconti-nuous alveolar epithelium. Combined with the typical morphology and immunohistochemical characteristics of CD10 positive, the diagnosis was PTL. The patient was followed up for 1 year without recurrence and discomfort. So far, the pathogenesis of PTL is unclear. The major hypotheses include hamartoma, variant of emphysema and clonal hyperplasia of stromal cells. Based on the study of our case and publication, we speculate that the hyperplasia of stromal cells located in the alveolar septa might be the first step to form the solid PTL. With the progression of the disease, a typical unilateral cystic nodule develops as a result of secondary cystic degeneration due to the occlusive valve effect. Surgery is the only option for diagnosis and treatment of PTL. The clinician should make an individualized operation plan according to the clinical manifestations, location and scope of the lesion, and preserve the surrounding normal lung tissue as much as possible while completely removing the lesion. There is a favorable prognosis.
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Placenta , Enfisema Pulmonar , Masculino , Humanos , Feminino , Gravidez , Pessoa de Meia-Idade , Hiperplasia/patologia , Placenta/patologia , Pulmão/patologia , Enfisema Pulmonar/patologia , Enfisema Pulmonar/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To explore the protocol for diagnosing thyroid nodules based on core needle biopsy (CNB) and study the biomarkers' application in distinguishing indeterminate samples. METHODS: Patients with thyroid nodules treated at Peking University First Hospital from 2015 to 2020 were reviewed. In the study, 598 cases with CNB and matched resected specimens were retrieved. According to "diagnostic categories of thyroid CNB" proposed by the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group, the CNB samples were diagnosed as follows: â , unsatisfactory; â ¡, benign; â ¢, indeterminate; â £, follicular neoplasm; â ¤, suspicious for malignancy; and â ¥, malignant. The samples of CNB â ¢ were stained by immunohistochemistry (IHC) using antibodies against CK19, Galectin-3, HBME-1, and CD56, and detected by next-generation sequencing (NGS) using an OncoAim® thyroid cancer multigene assay kit (Singlera Genomics) that detected 26 genes. Taking the resected specimens' classification as the gold standard, the predictive value of CNB for determining the malignancy of thyroid nodules and the biomarkers for distinguishing the samples of CNB â ¢ was calculated. RESULTS: The study included 598 patients, of which none were CNB â , 40 cases were CNB â ¡, 40 cases were CNB â ¢, 32 cases were CNB â £, 35 cases were CNB â ¤, and 451 cases were CNB â ¥. The predictive value of CNB â £ for determining follicular neoplasm was sensitivity (Sen) 100.00% and specificity (Sep) 100.00%, CNB â ¤-â ¥ for determining malignancy was Sen 94.55% and Sep 100.00%, CNB â ¡ for determining benign lesions was Sen 75.00% and Sep 99.80%. The predictive value of biomarkers for determining malignancy in cases of CNB â ¢ was Sen 96.30% and Sep 92.31% by NGS, and Sen 81.48% and Sep 92.30% by IHC. CONCLUSION: The Korean "diagnostic categories of thyroid CNB", which considers the histological specificity of CNB samples and the habits of clinicians, have strong operability, high diagnosis rate, and high clinical value. Under this framework, the cases of CNB â ¥ should be treated with surgical operation, the cases of CNB â ¤-â ¥ are recommended to be treated as malignant neoplasms, and the major cases of CNB â ¡ could be followed up without worrisome except the one considered malignant by ultrasound. The value of biomarkers in distinguishing the cases of CNB â ¢ is significant.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , BiomarcadoresRESUMO
Treatment of fibular fractures associated with extra-articular distal tibia fractures is technically challenging and the purpose of this study was to evaluate the use of intramedullary nail fixation of fibular fractures when associated with this fracture. Between January 2018 and December 2021, 33 patients presenting extra-articular distal tibia fractures and fibular fractures (AO/OTA 43A) were treated. Clinical and radiological data were collected during routine postoperative follow-ups. Thirty-one patients were monitored for a period of time ranging from 12 to 23 months, with an average follow-up of 17.5 ± 3.3 months. Fibular bone union took an average of 3.6 ± 0.9 months. At the last follow-up, the average fibular alignment and postoperative ankle talocrural angles were 1.8° and 9.1°, respectively. No detectable radiographic rotational malalignment and serious complications related to the fibular incision was observed. The average AOFAS and OMAS scores at the most recent follow-up were 88.3 ± 6.2 and 87.4 ± 6.0, respectively. Intramedullary nail fixation worked well to keep the fibula in place in fibular fractures connected to extra-articular distal tibia fractures.
Assuntos
Fraturas do Tornozelo , Fraturas da Tíbia , Humanos , Tíbia , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , FíbulaRESUMO
The clinical application of metagenomic next-generation sequencing (mNGS) in the diagnosis of unknown pathogenic infections and critical infections has become increasingly valuable. Due to the huge volume of mNGS data and the complexity of clinical diagnosis and treatment, mNGS has difficulties in data analysis and interpretation in practical application. Therefore, in the process of clinical practice, it is crucial to grasp the key points of bioinformatics analysis and establish a standardized bioinformatics analysis process, which is an important step in the transformation of mNGS from laboratory to clinic. At present, bioinformatics analysis of mNGS has made great progress, but with the high requirements of clinical standardization of bioinformatics analysis and the development of computer technology, bioinformatics analysis of mNGS is also facing new challenges. This article mainly elaborates on quality control, and identification and visualization of pathogenic bacteria.
Assuntos
Instituições de Assistência Ambulatorial , Sequenciamento de Nucleotídeos em Larga Escala , Biologia Computacional , Análise de Dados , Cabeça , Sensibilidade e EspecificidadeRESUMO
The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3-9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.
Assuntos
Escarlatina , Teorema de Bayes , Criança , Pré-Escolar , China/epidemiologia , Feminino , Previsões , Humanos , Incidência , Masculino , Modelos Estatísticos , Escarlatina/epidemiologia , Estações do AnoRESUMO
The security strength of an interference-based optical image cryptosystem with a designed amplitude modulator (AM) is evaluated. Compared to previous improved interference-based cryptosystems in which iterative or post-processing algorithms are involved, to remove the silhouette problem, a pre-designed AM is placed at the image plane to modulate the plaintext directly, which eliminates this drawback. Moreover, the AM is used as an additional private key, which enlarges the key space and further enhances the security system. However, we have noticed that one of the designed parameters in the AM has a low key sensitivity, which is fault-tolerant and is not required for precise reconstruction. Additionally, the AM is plaintext-independent, which means that the AM can be recovered first by using a pair of chosen plaintexts and the corresponding ciphertext. Based on these findings, we propose a hybrid algorithm that includes two chosen-plaintext attacks (CPAs) and a ciphertext-only attack (COA) to break the enhanced cryptosystem. Specially, CPAs with an impulse function and an arbitrarily given plaintext are proposed to retrieve two parameters in the AM. With the retrieved AM, information on the plaintext can be recovered from the corresponding ciphertext by two kinds of COAs without any knowledge of the private keys. To the best of our knowledge, this is the first time that the interference-based cryptosystem with a designed AM has been cracked successfully, which may provide potential evidence for further security improvements. Numerical simulations are carried out to validate the feasibility of the proposed attacks.