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1.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 377-383, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556822

RESUMO

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite Autoimune , Cirrose Hepática Biliar , Hepatopatia Gordurosa não Alcoólica , Síndrome de Sjogren , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome de Sjogren/complicações , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Fígado , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Inflamação/complicações , Doença Hepática Induzida por Substâncias e Drogas/complicações , Imunoglobulina M
2.
Clin Radiol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38589276

RESUMO

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

3.
Zhonghua Er Ke Za Zhi ; 62(5): 457-461, 2024 Apr 16.
Artigo em Chinês | MEDLINE | ID: mdl-38623014

RESUMO

Objective: To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods: From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results: Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples (χ2=5.72,P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum (χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions: From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

4.
Epigenetics ; 19(1): 2333660, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38564759

RESUMO

DNA methylation (DNAm) plays a crucial role in a number of complex diseases. However, the reliability of DNAm levels measured using Illumina arrays varies across different probes. Previous research primarily assessed probe reliability by comparing duplicate samples between the 450k-450k or 450k-EPIC platforms, with limited investigations on Illumina EPIC v1.0 arrays. We conducted a comprehensive assessment of the EPIC v1.0 array probe reliability using 69 blood DNA samples, each measured twice, generated by the Alzheimer's Disease Neuroimaging Initiative study. We observed higher reliability in probes with average methylation beta values of 0.2 to 0.8, and lower reliability in type I probes or those within the promoter and CpG island regions. Importantly, we found that probe reliability has significant implications in the analyses of Epigenome-wide Association Studies (EWAS). Higher reliability is associated with more consistent effect sizes in different studies, the identification of differentially methylated regions (DMRs) and methylation quantitative trait locus (mQTLs), and significant correlations with downstream gene expression. Moreover, blood DNAm measurements obtained from probes with higher reliability are more likely to show concordance with brain DNAm measurements. Our findings, which provide crucial reliability information for probes on the EPIC v1.0 array, will serve as a valuable resource for future DNAm studies.


Assuntos
Metilação de DNA , Locos de Características Quantitativas , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reprodutibilidade dos Testes , Ilhas de CpG
5.
Zhonghua Xue Ye Xue Za Zhi ; 45(2): 141-147, 2024 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-38604790

RESUMO

Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores não Relacionados , Sangue Fetal , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos
6.
Artigo em Chinês | MEDLINE | ID: mdl-38599639

RESUMO

Objective: To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC). Methods: This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. Results: A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%). Conclusion: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.


Assuntos
Albuminas , Anticorpos Monoclonais Humanizados , Neoplasias de Cabeça e Pescoço , Platina , Masculino , Feminino , Humanos , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Prospectivos , Paclitaxel/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Artigo em Chinês | MEDLINE | ID: mdl-38622021

RESUMO

Objective: To explore the clinical characteristics, pathological features, and diagnosis and treatment strategies of nasal chondromesenchymal hamartoma (NCMH) in infants and young children. Methods: A retrospective analysis was conducted on seven cases of NCMH infants and young children admitted to Beijing Children's Hospital, Capital Medical University from April 2015 to January 2022. The cohort included 5 males and 2 females, aged from 6 days to 2 years and 3 months. General information, clinical symptoms, imaging findings, treatment plans, postoperative complications, recurrence and follow-up time were collected, summarized and analyzed. Additionally, immunohistochemical characteristics of the lesion were examined. Results: The clinical symptoms of 7 children included nasal congestion, runny nose, open mouth breathing, snoring during sleep, difficulty feeding, and strabismus. All patients underwent electronic nasopharyngoscopy examination, with 5 cases of tumors located in the right nasal cavity and 2 cases in the left nasal cavity. No case of bilateral nasal cavity disease was found. All 7 patients underwent complete imaging examinations, with 5 patients underwent MRI and CT examinations, 1 patient underwent CT examination only, and 1 patient underwent MRI examination only. The CT results showed that all tumors were broad-based, with uneven density, multiple calcifications and bone remodeling, and some exhibited multiple cystic components. The MRI results showed that the tumor showed low signal on T1 weighted imaging and high or slightly high signal on T2 weighted imaging. All patients were diagnosed through histopathological examination and immunohistochemistry, including 7 cases of Ki-67 and SMA (+), 5 cases of S-100 and Vimentin (+), and all EMA and GFAP were negative. All patients underwent endoscopic resection surgery through the nasal approach, with 3 cases using navigation technology. Five cases of tumors were completely removed, and two cases of tumors were mostly removed. No nasal packing was performed after surgery, and no postoperative nasal, ocular, or intracranial complication occurred in all patients. Follow up assessments conducted 6 to 84 months post-surgery revealed no instances of tumor recurrence in any of the patients. Conclusions: The clinical symptoms of children with NCHM mainly depend on the size and location of the tumor. Nasal endoscopic surgery is the main treatment method. In cases where critical structures like the skull base or orbit are implicated, staged surgical interventions may be warranted. Long-term follow-up is strongly advised to monitor for any potential recurrence or complications.


Assuntos
Hamartoma , Doenças Nasais , Masculino , Lactente , Criança , Feminino , Humanos , Pré-Escolar , Cartilagens Nasais/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia , Doenças Nasais/diagnóstico , Hamartoma/diagnóstico , Hamartoma/cirurgia , Hamartoma/patologia
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(4): 413-419, 2024 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-38644257

RESUMO

Objective: To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults. Methods: A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk. Results: The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles (Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 (RR=1.11, 95%CI 1.01-1.22, P=0.023), TyG 8.6-8.9 (RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 (RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions: The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.


Assuntos
Glicemia , Hipertensão , População Rural , Triglicerídeos , Humanos , Hipertensão/epidemiologia , Hipertensão/sangue , Estudos Prospectivos , Pessoa de Meia-Idade , Masculino , Triglicerídeos/sangue , Adulto , Feminino , Fatores de Risco , Glicemia/análise , População Rural/estatística & dados numéricos , China/epidemiologia , Incidência , Estudos de Coortes , Pressão Sanguínea
9.
Ocul Immunol Inflamm ; : 1-8, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652891

RESUMO

PURPOSES: This study investigated the feasibility of adalimumab (ADA) dose reduction and withdrawal strategy in children with stable pediatric non-infectious uveitis (PNIU). METHODS: This open-label prospective pilot trial recruited 18 stable PNIU patients (33 eyes) between two and eighteen years old who were treated with standard doses of ADA (20/40 mg every 2 weeks) plus oral methotrexate. The interval of ADA injection was extended to 4 weeks and followed up for 24 weeks. If the uveitis remained stable, ADA was discontinued and followed up for another 24 weeks. ADA was considered successfully stopped if no relapse occurred during this period. The relapse-free survival rate, best corrected visual acuity (BVCA), anterior chamber cell (ACC), vitritis, macular thickness (MT), and serum ADA levels were evaluated. Approval Number: 2021KYPJ201. ClinicalTrials.gov identifier: NCT05155592. RESULTS: The relapse-free survival rate was 22.2% (4/18) at 48 weeks. 33.3% (6/18) of patients relapsed when ADA was given every 4 weeks, while 44.5% of patients (8/18) relapsed after ADA was stopped. The four patients successfully withdrawn from ADA were all diagnosed with BD. No statistically significant differences (p > 0.05) were observed in BCVA and MT between baseline and final follow-up. The proportion of ACC and vitritis exhibited an upward trend (p < 0.05) during follow-up. Serum ADA gradually decreased to zero during follow-up in both non-recurrence and recurrence groups. CONCLUSIONS: In PNIU children who reached remission for 6 months, ADA dose reduction and withdrawal were associated with a high risk of inflammation recurrence. Timely adjustment of ADA to the last effective dosage frequency can regain control of the inflammation. Detection of ADA serum levels in patients with recurrence may help find the appropriate interval of ADA use.

10.
Phys Rev Lett ; 132(14): 141901, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38640399

RESUMO

Using e^{+}e^{-} collision data corresponding to an integrated luminosity of 7.33 fb^{-1} recorded by the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, we present an analysis of the decay D_{s}^{+}→π^{+}π^{-}e^{+}ν_{e}, where the D_{s}^{+} is produced via the process e^{+}e^{-}→D_{s}^{*±}D_{s}^{∓}. We observe the f_{0}(980) in the π^{+}π^{-} system and the branching fraction of the decay D_{s}^{+}→f_{0}(980)e^{+}ν_{e} with f_{0}(980)→π^{+}π^{-} measured to be (1.72±0.13_{stat}±0.10_{syst})×10^{-3}, where the uncertainties are statistical and systematic, respectively. The dynamics of the D_{s}^{+}→f_{0}(980)e^{+}ν_{e} decay are studied with the simple pole parametrization of the hadronic form factor and the Flatté formula describing the f_{0}(980) in the differential decay rate, and the product of the form factor f_{+}^{f_{0}}(0) and the c→s Cabibbo-Kobayashi-Maskawa matrix element |V_{cs}| is determined for the first time to be f_{+}^{f_{0}}(0)|V_{cs}|=0.504±0.017_{stat}±0.035_{syst}. Furthermore, the decay D_{s}^{+}→f_{0}(500)e^{+}ν_{e} is searched for the first time but no signal is found. The upper limit on the branching fraction of D_{s}^{+}→f_{0}(500)e^{+}ν_{e}, f_{0}(500)→π^{+}π^{-} decay is set to be 3.3×10^{-4} at 90% confidence level.

11.
Mutagenesis ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606763

RESUMO

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

12.
Phys Rev Lett ; 132(13): 131901, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613263

RESUMO

We present cross sections for the reaction e^{+}e^{-}→K_{S}^{0}K_{L}^{0} at center-of-mass energies ranging from 3.51 to 4.95 GeV using data samples collected in the BESIII experiment, corresponding to a total integrated luminosity of 26.5 fb^{-1}. The ratio of neutral-to-charged kaon form factors at large momentum transfers (12

13.
Phys Rev Lett ; 132(13): 131903, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613307

RESUMO

We perform for the first time an amplitude analysis of the decay D^{+}→K_{S}^{0}π^{+}η and report the observation of the decay D^{+}→K_{S}^{0}a_{0}(980)^{+} using 2.93 fb^{-1} of e^{+}e^{-} collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector. As the only W-annihilation-free decay among D to a_{0}(980) pseudoscalar, D^{+}→K_{S}^{0}a_{0}(980)^{+} is the ideal decay in extracting the contributions of the W-emission amplitudes involving a_{0}(980) and to study the final-state interactions. The absolute branching fraction of D^{+}→K_{S}^{0}π^{+}η is measured to be (1.27±0.04_{stat}±0.03_{syst})%. The branching fractions of intermediate processes D^{+}→K_{S}^{0}a_{0}(980)^{+} with a_{0}(980)^{+}→π^{+}η and D^{+}→π^{+}K[over ¯]_{0}^{*}(1430)^{0} with K[over ¯]_{0}^{*}(1430)^{0}→K_{S}^{0}η are measured to be (1.33±0.05_{stat}±0.04_{syst})% and (0.14±0.03_{stat}±0.01_{syst})%, respectively.

14.
Eur Rev Med Pharmacol Sci ; 28(7): 2906-2922, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639528

RESUMO

OBJECTIVE: Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis. Minichromosome maintenance genes (MCM2-7) crucial for DNA replication are significant biomarkers for various tumor types; however, their roles in TNBC remain underexplored. MATERIALS AND METHODS: We utilized four TNBC-related GEO databases to examine MCM2-7 gene expression and predict its prognosis in TNBC, performing single-cell analysis and GSEA to discover MCM6's potential function. The Cancer Dependency Map gene effect scores and CCK8 assay were used to assess MCM6's impact on TNBC cell proliferation. The correlations between MCM6 expression, immune infiltrates, and immune cells were also analyzed. WGCNA and LASSO Cox regression built a risk score model predicting TNBC patient survival based on MCM6-related gene expression. RESULTS: MCM2-7 gene expression was higher in TNBC tissues compared to adjacent normal tissues. High MCM6 expression correlated with shorter TNBC patient survival time. GSEA and single-cell analysis revealed a relationship between elevated MCM6 expression and the cell cycle pathway. MCM6 knockdown inhibited TNBC cell proliferation. A risk model featuring MCM6, CDC23, and CCNB1 effectively predicts TNBC patient survival. CONCLUSIONS: MCM6 overexpression in TNBC links to a worse prognosis and reduced cell proliferation upon MCM6 knockdown. We developed a risk score model based on MCM6-related genes predicting TNBC patient prognosis, potentially assisting future treatment strategies.


Assuntos
Componente 6 do Complexo de Manutenção de Minicromossomo , Neoplasias de Mama Triplo Negativas , Humanos , Biomarcadores , Ciclo Celular , Proliferação de Células/genética , Componente 6 do Complexo de Manutenção de Minicromossomo/genética , Componente 6 do Complexo de Manutenção de Minicromossomo/metabolismo , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia
15.
Eur Rev Med Pharmacol Sci ; 28(7): 2629, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38639497

RESUMO

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (10): 4462-4470-DOI: 10.26355/eurrev_202305_32452-published online on May 29, 2023. After publication, the authors have discovered a mistake in the number of male and female patients in the Patients and Methods section. Therefore, the following sentence "58 male patients and 42 female patients" is corrected into "71 male and 39 female patients". The corrections do not affect the article's results and conclusion as patients are reported correctly in the text as well as figures and tables. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32452.

16.
Zhonghua Yi Xue Za Zhi ; 104(14): 1160-1167, 2024 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-38583047

RESUMO

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Hepatocelular/terapia , DNA Viral/análise , DNA Viral/farmacologia , DNA Viral/uso terapêutico , Neoplasias Hepáticas/terapia , Estudos Retrospectivos , Vírus da Hepatite B/genética , Prognóstico , Antivirais/uso terapêutico
17.
Zhonghua Yi Xue Za Zhi ; 104(15): 1310-1315, 2024 Apr 16.
Artigo em Chinês | MEDLINE | ID: mdl-38637167

RESUMO

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group (P<0.05).Preoperative TIA (OR=4.514, 95%CI: 1.920-10.611), old cerebral infarction (OR=2.856,95%CI:1.176-6.936), A1 stenosis (OR=7.027,95%CI:1.877-26.308), M1 stenosis (OR=6.968,95%CI:2.162-22.459), abnormal PCA (OR=4.114,95%CI:1.330-12.728)and unstable compensation (OR=4.488,95%CI:1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P<0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization.


Assuntos
Revascularização Cerebral , Ataque Isquêmico Transitório , Doença de Moyamoya , Adulto , Humanos , Masculino , Feminino , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Constrição Patológica/complicações , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Infarto Cerebral , Fatores de Risco , Resultado do Tratamento
19.
Phys Rev Lett ; 132(10): 101801, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518329

RESUMO

Using (10087±44)×10^{6} J/ψ events collected with the BESIII detector, numerous Ξ^{-} and Λ decay asymmetry parameters are simultaneously determined from the process J/ψ→Ξ^{-}Ξ[over ¯]^{+}→Λ(pπ^{-})π^{-}Λ[over ¯](n[over ¯]π^{0})π^{+} and its charge-conjugate channel. The precisions of α_{Λ0} for Λ→nπ^{0} and α[over ¯]_{Λ0} for Λ[over ¯]→n[over ¯]π^{0} compared to world averages are improved by factors of 4 and 1.7, respectively. The ratio of decay asymmetry parameters of Λ→nπ^{0} to that of Λ→pπ^{-}, ⟨α_{Λ0}⟩/⟨α_{Λ-}⟩, is determined to be 0.873±0.012_{-0.010}^{+0.011}, where the first and the second uncertainties are statistical and systematic, respectively. The ratio is smaller than unity more than 5σ, which signifies the existence of the ΔI=3/2 transition in Λ for the first time. Besides, we test for CP symmetry in Ξ^{-}→Λπ^{-} and in Λ→nπ^{0} with the best precision to date.

20.
Eur Rev Med Pharmacol Sci ; 28(5): 1837-1846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497866

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.


Assuntos
Leucemia Mieloide Aguda , Trombocitopenia , Idoso , Humanos , Qualidade de Vida , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Sulfonamidas/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , 60410
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