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This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}â³0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}â²|Δm_{41}^{2}|â²0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}â²|Δm_{41}^{2}|â²0.2 eV^{2}.
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AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Imagen por Resonancia Magnética , Humanos , Colangiocarcinoma/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Pronóstico , Anciano , Estudios Retrospectivos , AdultoRESUMEN
OBJECTIVES: This study aimed to investigate global, regional, and national trends in osteoarthritis disability-adjusted life years (DALYs) from 1990 to 2019, identify the burden of osteoarthritis in different age groups, and assess age, period, and cohort effects on osteoarthritis DALYs. STUDY DESIGN: A comprehensive analysis of the Global Burden of Disease Study 2019 data, covering 204 countries and territories. METHODS: We conducted a comprehensive analysis using data from the Global Burden of Disease Study 2019, encompassing 204 countries and territories. Age-standardized DALY rates were calculated, and the age-period-cohort model was employed to examine the age, period, and cohort effects on osteoarthritis DALYs. The annual percentage change (APC) and average annual percentage change (AAPC) were estimated to evaluate trends in DALYs. RESULTS: Globally, osteoarthritis DALYs increased by 114.48 % between 1990 and 2019, with an age-standardized DALY rate growth of 3.3 %. The largest relative growth in DALYs occurred in Middle and Low-middle Socio-Demographic Index (SDI) regions. DALYs increased significantly in almost all age-specific groups, particularly among 45-74 years old age groups. Age, period, and cohort effects analysis revealed a general increase in osteoarthritis DALYs risk over time, with some variations by SDI quintiles and sex. The steepest increase in DALYs occurred in the 30-34 years age group, and the trend attenuated with increasing age. Males showed significantly slower DALYs growth than females in age groups with non-overlapping 95 % confidence intervals. Age effects were consistently higher in females, especially in high-SDI countries. Period and cohort effects generally demonstrated a climbing risk of osteoarthritis DALYs across different SDI quintiles, with more pronounced increases in lower-SDI regions. CONCLUSIONS: Our findings highlight the substantial and increasing burden of osteoarthritis at global, regional, and national levels from 1990 to 2019, with significant variations by age, period, and cohort. These results underscore the importance of developing targeted public health strategies and interventions to address the growing impact of osteoarthritis, particularly in lower-SDI regions and among older populations.
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Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Años de Vida Ajustados por Calidad de Vida , Factores Socioeconómicos , Salud Pública , Salud Global , IncidenciaRESUMEN
Lushan Yunwu tea quality is limited by soil acidity and sterility. This article examined a 3-year localization experiment at 1100 m altitude to demonstrate the sustainable management of conditioners, calcium magnesium phosphate (P), rapeseed cake (C), and combination application (P + C) by one-time application on the soil-tea system in Mount Lushan. The study found that conditioners (P, C, P + C) reduced soil acidification and maintained a pH of 4.75-5.34, ideal for tea tree development for 3 years. Phosphorus activation coefficient (PAC), nitrogen activation coefficient (NAC), and organic matter (OM) content were significantly higher (P < 0.05) in the first year after conditioner treatment, with P + C being the best. After P + C, PAC, NAC, and OM rose by 31.25%, 47.70%, and 10.06 g kg-1 compared to CK. In comparison to the CK, tea's hundred-bud weight (BW), free amino acids (AA), tea polyphenols (TPC), and chlorophyll (Chl) content of P + C treatment got 29.98%, 14.41%, 22.49%, and 28.85% increase compared to that of the CK, respectively. In the second year, the three treatments of P, C and P + C still had significant moderating effects on the physicochemical properties of the soil and the quality indexes of the tea leaves. The PAC of the soil under the three treatments increased by 0.06%, 0.07% and 0.18%, respectively, as compared to the control.P + C increased BW, AA, TPC and Chl of tea for 2 years. Three conditioners had 2-year regulatory impacts on soil fertility indicators, tea output, and quality. C and P + C both increased soil OM by 18.59% and 21.78% compared to CK in the third year, outperforming P treatment. Redundancy analysis revealed that the primary physicochemical factors influencing tea output and quality were soil OM and pH, with available phosphorus, urease, acid phosphatase, and available nitrogen following closely afterwards.
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Suelo , Suelo/química , China , Té/química , Camellia sinensis/química , Concentración de Iones de Hidrógeno , Fertilizantes , Brassica rapa , Fosfatos , Nitrógeno , Clorofila , Fósforo/análisisRESUMEN
Degenerative lumbar scoliosis (DLS) is a spinal deformity characterized primarily by abnormal curvature of the lumbar vertebrae, commonly occurring in individuals aged 50 and above. Its pathogenesis involves various factors, including intervertebral disc degeneration, ligament and muscle degradation, as well as genetic and environmental elements. In terms of treatment, non-surgical treatments such as pharmacotherapy, physical therapy, and exercise are regarded as the primary approach. However, for severe cases, individualized surgical intervention is also a viable option, and reasonable classification is the key to surgical decision-making. Current research predominantly emphasizes the osseous structural aspects of the spine, neglecting neural and muscular factors. Future interdisciplinary research is expected to explore more comprehensive and effective treatment modalities, aiding in the restoration of spinal cord function in patients.
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Degeneración del Disco Intervertebral , Vértebras Lumbares , Escoliosis , Humanos , Escoliosis/terapia , Degeneración del Disco Intervertebral/terapiaRESUMEN
Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.
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Neoplasias Óseas , Reordenamiento Génico , Hibridación Fluorescente in Situ , Proteína EWS de Unión a ARN , Neoplasias de los Tejidos Blandos , Humanos , Proteína EWS de Unión a ARN/genética , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Hibridación Fluorescente in Situ/métodos , Neoplasias Óseas/genética , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/diagnóstico , Histiocitoma Fibroso Maligno/patología , Sarcoma de Ewing/genética , Sarcoma de Ewing/diagnósticoRESUMEN
Objective: To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS). Methods: Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor). Results: Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group (P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions: Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.
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Neoplasias Óseas , Fibrosarcoma , Osteosarcoma , Sarcoma , Humanos , Femenino , Masculino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Amplificación de Genes , Hibridación Fluorescente in Situ , Osteosarcoma/diagnóstico , Osteosarcoma/genética , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Proteínas Proto-Oncogénicas c-mdm2/genéticaRESUMEN
Objective: To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). Methods: The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. Results: The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (n=4), brachial plexus (n=2) or multiple nerves (n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of ß-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions: NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.
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Coristoma , Fibromatosis Agresiva , Mutación , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Fibromatosis Agresiva/genética , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/metabolismo , Fibromatosis Agresiva/cirugía , Masculino , Femenino , Niño , Estudios Retrospectivos , Lactante , Adolescente , Preescolar , Coristoma/patología , Coristoma/genética , Adulto Joven , Plexo Braquial/patología , Plexo Braquial/cirugía , Nervio Ciático/patologíaRESUMEN
Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2â¶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.
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Trastornos del Desarrollo Sexual , Gónadas , Humanos , Masculino , Femenino , Adolescente , Gónadas/patología , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/patología , Testículo/patología , Ovario/patología , CariotipificaciónRESUMEN
Objective: To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses. Methods: Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis. Results: There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur (n=4), humerus (n=5) and iliac bone (n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions: EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.
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Quistes Óseos Aneurismáticos , Quistes Óseos , Femenino , Masculino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Quistes Óseos Aneurismáticos/diagnóstico por imagen , Quistes Óseos Aneurismáticos/genética , Quistes Óseos Aneurismáticos/cirugía , Hibridación Fluorescente in Situ , Estudios Retrospectivos , Quistes Óseos/diagnóstico por imagen , Quistes Óseos/genética , Diagnóstico DiferencialRESUMEN
Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease's characteristics and antiviral treatment strategies, are discussed here.
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Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Tolerancia Inmunológica , Hepatitis B/tratamiento farmacológicoRESUMEN
Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class â /â ¡/â ¢/â £ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.
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Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico , Arteria Pulmonar , Embolia Pulmonar/diagnóstico , Angioplastia de Balón/métodos , Hemodinámica , Enfermedad Crónica , Resultado del TratamientoRESUMEN
Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.
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Reactores Nucleares , UranioRESUMEN
We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.
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Intramuscular fat (IMF) is a significant marker for pork quality. The Anqing Six-end-white pig has the characteristics of high meat quality and IMF content. Owing to the influence of European commercial pigs and a late start in resource conservation, the IMF content within local populations varies between individuals. This study analyzed the longissimus dorsi transcriptome of purebred Anqing Six-end-white pigs with varying IMF content to recognize differentially expressed genes. We identified 1528 differentially expressed genes between the pigs with high (H) and low (L) IMF content. Based on these data, 1775 Gene Ontology terms were significantly enriched, including lipid metabolism, modification and storage, and regulation of lipid biosynthesis. Pathway analysis revealed 79 significantly enriched pathways, including the Peroxisome proliferator-activated receptor and mitogen-activated protein kinase signaling pathways. Moreover, gene set enrichment analysis indicated that the L group had increased the expression of genes related to ribosome function. Additionally, the protein-protein interaction network analyses revealed that VEGFA, KDR, LEP, IRS1, IGF1R, FLT1 and FLT4 were promising candidate genes associated with the IMF content. Our study identified the candidate genes and pathways involved in IMF deposition and lipid metabolism and provides data for developing local pig germplasm resources.
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Transcriptoma , Porcinos , Animales , Análisis de Secuencia de ARNRESUMEN
INTRODUCTION: This study explored the impact of online learning during the coronavirus disease 2019 (COVID-19) pandemic on asthenopia and vision impairment in students, with the aim of establishing a theoretical basis for preventive approaches to vision health. METHODS: This balanced panel study enrolled students from western rural China. Participant information was collected before and during the COVID-19 pandemic via questionnaires administered at local vision care centres, along with clinical assessments of visual acuity. Paired t tests and fixed-effects models were used to analyse pandemic-related differences in visual status. RESULTS: In total, 128 students were included (mean age before pandemic, 11.82 ± 1.46 years). The mean total screen time was 3.22 ± 2.90 hours per day during the pandemic, whereas it was 1.97 ± 1.90 hours per day in the pre-pandemic period (P<0.001). Asthenopia prevalence was 55% (71/128) during the pandemic, and the mean visual acuity was 0.81 ± 0.30 logarithm of the minimum angle of resolution; these findings indicated increasing vision impairment, compared with the pre-pandemic period (both P<0.001). Notably, asthenopia prevalence increased by two- to three-fold, compared with the pre-pandemic period. An increase in screen time while learning was associated with an increase in asthenopia prevalence (P=0.034). CONCLUSION: During the COVID-19 pandemic, students spent more time on online classes, leading to worse visual acuity and vision health. Students in this study reported a significant increase in screen time, which was associated with increasing asthenopia prevalence and worse vision impairment. Further research is needed regarding the link between online classes and vision problems.
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Astenopía , COVID-19 , Humanos , Niño , Adolescente , COVID-19/epidemiología , Astenopía/epidemiología , Pandemias , Prevalencia , Estudiantes , China/epidemiologíaRESUMEN
Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.
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Neoplasias Colorrectales , Animales , Ratones , Protocolos de Quimioterapia Combinada Antineoplásica , Proteínas Reguladoras de la Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fluorouracilo/farmacología , Irinotecán/uso terapéutico , Antígeno Ki-67 , Oxaliplatino , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/uso terapéuticoRESUMEN
Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.
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Carcinoma Ductal Pancreático , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Neoplasias Pancreáticas , Ratones , Animales , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical , Neoplasias PancreáticasRESUMEN
Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage â £: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
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Mesotelioma Maligno , Humanos , Pronóstico , Nomogramas , Estudios Retrospectivos , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: To analyze the cement flow in the abutment margin-crown platform switching structure by using the three-dimensional finite element analysis, in order to prove that whether the abutment margin-crown platform switching structure can reduce the inflow depth of cement in the implantation adhesive retention. METHODS: By using ANSYS 19.0 software, two models were created, including the one with regular margin and crown (Model one, the traditional group), and the other one with abutment margin-crown platform switching structure (Model two, the platform switching group). Both abutments of the two models were wrapped by gingiva, and the depth of the abutment margins was 1.5 mm submucosal. Two-way fluid structure coupling calculations were produced in two models by using ANSYS 19.0 software. In the two models, the same amount of cement were put between the inner side of the crowns and the abutments. The process of cementing the crown to the abutment was simulated when the crown was 0.6 mm above the abutment. The crown was falling at a constant speed in the whole process spending 0.1 s. Then we observed the cement flow outside the crowns at the time of 0.025 s, 0.05 s, 0.075 s, 0.1 s, and measured the depth of cement over the margins at the time of 0.1 s. RESULTS: At the time of 0 s, 0.025 s, 0.05 s, the cements in the two models were all above the abutment margins. At the time of 0.075 s, in Model one, the gingiva was squeezed by the cement and became deformed, and then a gap was formed between the gingiva and the abutment into which the cement started to flow. In Model two, because of the narrow neck of the crown, the cement flowed out from the gingival as it was pressed by the upward counterforce from the gingival and the abutment margin. At the time of 0.1 s, in Model one, the cement continued to flow deep inside with the gravity force and pressure, and the depth of the cement over the margin was 1 mm. In Model two, the cement continued to flow out from the gingival at the time of 0.075 s, and the depth of the cement over the margin was 0 mm. CONCLUSION: When the abutment was wrapped by the gingiva, the inflow depth of cement in the implantation adhesive retention can be reduced in the abutment margin-crown platform switching structure.