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1.
Nature ; 601(7892): 201-204, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35022591

RESUMEN

The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars2,3, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion4. Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients5-8. Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.

2.
J Clin Periodontol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783632

RESUMEN

AIM: This study aimed to identify the risk factors for gingival invagination during orthodontic treatment after premolar extraction. MATERIALS AND METHODS: The medical records of 135 patients who had undergone interdental space closure after premolar extraction were collected, and cone beam computed tomography was performed to determine the presence of gingival invagination. The risk factors were examined using mixed-effects models and generalized propensity score weighting (GPSW) to develop a predictive model. RESULTS: Univariate analysis revealed that the extraction site, buccal bone thickness 4 mm apical to the cemento-enamel junction (MB1), mid-root buccal bone thickness (MB2) and vertical skeletal relationships were related to gingival invagination (p < .05). Furthermore, a subsequent multivariable mixed-effects model analysis indicated a significantly increased risk of gingival invagination at MB1 < 1 mm (p < .001; odds ratio [ORMB1≤0.5mm] = 29.304; 95% confidence interval [CI]: 8.986-93.807; OR0.5

3.
J Endocrinol Invest ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358462

RESUMEN

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.

4.
Zhonghua Yi Xue Za Zhi ; 104(7): 507-513, 2024 Feb 20.
Artículo en Zh | MEDLINE | ID: mdl-38317362

RESUMEN

Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.


Asunto(s)
Citopenia , Linfopenia , Mieloma Múltiple , Neutropenia , Receptores Quiméricos de Antígenos , Trombocitopenia , Femenino , Humanos , Masculino , Anemia , Anticuerpos/uso terapéutico , Antígeno de Maduración de Linfocitos B/uso terapéutico , Mieloma Múltiple/terapia , Pronóstico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano
5.
Zhonghua Yi Xue Za Zhi ; 104(16): 1403-1409, 2024 Apr 23.
Artículo en Zh | MEDLINE | ID: mdl-38644291

RESUMEN

Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.


Asunto(s)
Neoplasias Encefálicas , Biopsia Guiada por Imagen , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Glioma/patología , Adulto , Anciano , Encéfalo/patología , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/métodos
6.
Zhonghua Yi Xue Za Zhi ; 104(27): 2521-2528, 2024 Jul 16.
Artículo en Zh | MEDLINE | ID: mdl-38978376

RESUMEN

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Antígenos HLA , Leucemia , Humanos , Femenino , Masculino , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Pronóstico , Estudios Retrospectivos , Preescolar , Niño , Leucemia/genética , Leucemia/terapia , Antígenos HLA/genética , Enfermedad Injerto contra Huésped/etiología , Donantes de Tejidos , Prueba de Histocompatibilidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos
7.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 709-715, 2024 Jul 08.
Artículo en Zh | MEDLINE | ID: mdl-38955703

RESUMEN

Objective: To investigate the value of histological evaluation in predicting endoscopic relapse among patients with ulcerative colitis (UC) who were in endoscopic remission, and to compare the usefulness of various histological scoring systems. Methods: Histological sections from 61 patients with UC who were in endoscopic remission were retrospectively analyzed, at Peking University Third Hospital, Beijing, China from January 2015 to June 2021. They were subdivided into endoscopic persistent remission group (remission group, n=31, Mayo endoscopic score 0) and endoscopic relapse group (relapse group, n=30, Mayo endoscopic score≥1) according to the results of the first endoscopic reexamination after the biopsy. Histological evaluation was performed using the Geboes score (GS) and its simplified version (SGS), the Nancy index (NI) and the Robarts histopathological index (RHI). The median and maximum histological scores for each case in all biopsies were recorded. Univariate comparisons were performed using chi-squares and multivariate analysis using binary logistic regression. The values of four histological evaluation systems for predicting endoscopic relapse among UC patients in endoscopic remission were analyzed using receiver operating characteristic (ROC) curves. Results: Significant differences were observed between the remission and relapse groups. The differences were more pronounced in the maximum histological scores; the mean and highest results of area under the ROC curve scores (AUC) for GS, SGS, NI, and RHI were 0.657, 0.668, 0.682, 0.691, and 0.866, 0.863, 0.864, 0.869, respectively. The differences were statistically significant (P<0.05). The corresponding best cut-offs were GS≥2B.1, SGS≥2B.1, NI≥2, and RHI≥2.5, respectively, which meant mild active inflammation histologically, while there was no statistical difference of AUC among the four histological scoring indices (P>0.05). Univariate and multivariate analyses revealed statistically significant differences in the number of neutrophils in the epithelium and lamina propria (P<0.05). Conclusions: Biopsies from UC patients in endoscopic remission may still have histological active inflammation which appears to correlate with endoscopic relapse. Four commonly used histological scoring systems can be used to assess the risk of endoscopic relapse among UC patients in endoscopic remission. The patients who more likely have endoscopic relapse seem to have a histological score greater than the cut-off value (i.e., mild histological activity). The maximum histological scores can accurately predict the risk of endoscopic relapse, while the presence of epithelial and laminar propria neutrophil infiltrates can independently predict the endoscopic relapse in these patients. Considering the utility and convenience in routine practice, NI is recommended for evaluating histological inflammatory activity.


Asunto(s)
Colitis Ulcerosa , Recurrencia , Colitis Ulcerosa/patología , Colitis Ulcerosa/cirugía , Humanos , Estudios Retrospectivos , Biopsia , Colonoscopía , Inducción de Remisión , Curva ROC , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Femenino , Masculino , Adulto
8.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(2): 172-177, 2024 Feb 12.
Artículo en Zh | MEDLINE | ID: mdl-38309970

RESUMEN

The use of lung ultrasound in the screening, diagnosis, and evaluation of interstitial lung disease has been relatively well studied, but has not been widely accepted and applied in clinical practice. There are also some differences in the examination methods applied in these studies. This paper summarized the application, advantages, and disadvantages of lung ultrasound in the diagnosis and follow-up of interstitial lung disease by comprehensively reviewing the examination methods, research results and progress of new technologies of lung ultrasound in interstitial lung disease.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Ultrasonografía/métodos , Tórax
9.
J Infect Dis ; 228(5): 555-563, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37062677

RESUMEN

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) possess mutations that prevent antibody therapeutics from maintaining antiviral binding and neutralizing efficacy. Monoclonal antibodies (mAbs) shown to neutralize Wuhan-Hu-1 SARS-CoV-2 (ancestral) strain have reduced potency against newer variants. Plasma-derived polyclonal hyperimmune drugs have improved neutralization breadth compared with mAbs, but lower titers against SARS-CoV-2 require higher dosages for treatment. We previously developed a highly diverse, recombinant polyclonal antibody therapeutic anti-SARS-CoV-2 immunoglobulin hyperimmune (rCIG). rCIG was compared with plasma-derived or mAb standards and showed improved neutralization of SARS-CoV-2 across World Health Organization variants; however, its potency was reduced against some variants relative to ancestral, particularly omicron. Omicron-specific antibody sequences were enriched from yeast expressing rCIG-scFv and exhibited increased binding and neutralization to omicron BA.2 while maintaining ancestral strain binding and neutralization. Polyclonal antibody libraries such as rCIG can be utilized to develop antibody therapeutics against present and future SARS-CoV-2 threats.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2/genética , Anticuerpos Monoclonales/uso terapéutico , Antivirales , Saccharomyces cerevisiae , Anticuerpos Neutralizantes/uso terapéutico , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Antivirales/uso terapéutico
10.
Artículo en Zh | MEDLINE | ID: mdl-38538234

RESUMEN

Objective: To investigate the occurrence of low back work-related musculoskeletal disorders (WMSDs) among workers in a container manufacturing factory, and to explore the influencing factors. Methods: In June 2022, 952 workers from a container factory were selected as the research objects by cluster random sampling. Through questionnaire survey, the incidence of low back WMSDs symptoms among workers in the past one year was collected, and the influencing factors of low back WMSDs were analyzed by logistic regression. Results: The incidence rate of low back WMSDs was 46.7% (445/952). The factors with higher exposure at work were frequent slight bending (77.0%, 733/952), frequent overtime (74.1%, 705/952), and the need to turn around while working (62.3%, 593/952). Multivariate logistic regression analysis showed that age over 40 years old, smoking, drinking, often bending over slightly, sitting for a long time, maintaining a large bending posture for a long time, often working overtime, limited operating space, and there was always a need to complete conflicting things in the container manufacturing factory workers were the risks of increasing the low back WMSDs (OR=1.68, 1.96, 2.47, 1.49, 1.84, 2.11, 1.90, 1.82, 2.00, P<0.05). Standing at work, always friendly colleagues, and always supportive and helpful leaders were protective factors for low back WMSDs (OR=0.60, 0.32, 0.40, P<0.05) . Conclusion: The incidence of low back WMSDs symptoms in container manufacturing workers is high, and work-related factors such as frequent slight bending, long time holding large bending posture and limited operating space are the focus of ergonomic intervention in container manufacturing enterprises.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Humanos , Adulto , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/complicaciones , Factores de Riesgo , Prevalencia , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/etiología , Encuestas y Cuestionarios , Mentol , Instalaciones Industriales y de Fabricación
11.
Osteoarthritis Cartilage ; 31(6): 819-828, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36889626

RESUMEN

OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.


Asunto(s)
Osteoartritis de la Rodilla , Masculino , Femenino , Humanos , Índice de Masa Corporal , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/genética , Estudio de Asociación del Genoma Completo , Causalidad , Articulación de la Rodilla , Polimorfismo de Nucleótido Simple
12.
Invest New Drugs ; 41(5): 737-750, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37646958

RESUMEN

Previously, we generated a novel bispecific antibody (BsAb) simultaneously targeting both c-MET and PD-1 (PDCD1), which can bridge T cells and c-MET positive tumor cells. However, the specific mechanisms and antitumor activities of the BsAb against c-MET/PD-L1 (CD274) positive colorectal cancer (CRC) is not completely understood. In this study, in addition to the tumor intrinsic mechanism investigation with molecular biology assay in vitro, a humanized mouse model was used to evaluate antitumor activity of the BsAb in vivo. The BsAb could inhibit c-MET/PD-L1+ CRC cell migration and show strong antitumor activity against HCT116 tumors in mice, potentially by inducing the degradation of c-MET protein in a dose and time-dependent manner. The BsAb could suppress the phosphorylation of c-MET downstream proteins GRB2-associated-binding protein 1 (Gab1) and focal adhesion kinase (FAK). Considering the tumor extrinsic mechanism, the BsAb may promote phagocytosis of macrophage. Furthermore, the level of plasma exosomal-c-MET/PD-L1 is able to distinguish CRC patients from healthy controls. In summary, the BsAb exhibited potent anti-tumor activities by two distinguished mechanisms: inhibition of c-MET signal transduction and promotion of macrophage-mediated phagocytosis. Our BsAb may provide a novel therapeutic agent for patients with c-MET/PD-L1+ CRC, and the status of exosomal-c-MET/PD-L1 can serve as a biomarker to predict responsiveness to treatment of our BsAb.

13.
Phys Rev Lett ; 131(2): 025101, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37505952

RESUMEN

A novel compact high-flux neutron generator with a pitcher-catcher configuration based on laser-driven collisionless shock acceleration (CSA) is proposed and experimentally verified. Different from those that previously relied on target normal sheath acceleration (TNSA), CSA in nature favors not only acceleration of deuterons (instead of hydrogen contaminants) but also increasing of the number of deuterons in the high-energy range, therefore having great advantages for production of high-flux neutron source. The proof-of-principle experiment has observed a typical CSA plateau feature from 2 to 6 MeV in deuteron energy spectrum and measured a forward neutron flux with yield 6.6×10^{7} n/sr from the LiF catcher target, an order of magnitude higher than the compared TNSA case, where the laser intensity is 10^{19} W/cm^{2}. Self-consistent simulations have reproduced the experimental results and predicted that a high-flux forward neutron source with yield up to 5×10^{10} n/sr can be obtained when laser intensity increases to 10^{21} W/cm^{2} under the same laser energy.

14.
Clin Radiol ; 78(9): 703-714, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37365114

RESUMEN

AIM: To evaluate the role of quantitative cardiac magnetic resonance imaging (CMRI) parameters in myocarditis, including acute and chronic myocarditis (AM and CM), for children and adolescents. MATERIALS AND METHODS: PRISMA principles were followed. PubMed, EMBASE, Web of Science, Cochrane Library, and grey literature were searched. The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist were utilised for quality assessment. Quantitative CMRI parameters were extracted and a meta-analysis was performed in comparison with healthy controls. The overall effect size was measured as the weighted mean difference (WMD). RESULTS: Ten quantitative CMRI parameters of seven studies were analysed. Compared with the control group, the myocarditis group reported longer native T1 relaxation time (WMD=54.00, 95% confidence interval [CI]: 33.21,74.79, p<0.001), longer T2 relaxation time (WMD=2.13, 95% CI: 0.98, 3.28, p<0.001), increased extracellular volume (ECV; WMD=3.13, 95% CI: 1.34,4.91, p=0.001), elevated early gadolinium enhancement (EGE) ratio (WMD=1.47, 95% CI: 0.65,2.28, p<0.001), and increased T2-weighted ratio (WMD=0.43, 95% CI: 0.21,0.64, p<0.001). The AM group had longer native T1 relaxation times (WMD=72.02, 95% CI: 32.78,111.27, p<0.001), increased T2-weighted ratios (WMD=0.52, 95% CI: 0.21,0.84 p=0.001), and impaired left ventricular ejection fractions (LVEF; WMD=-5.84, 95% CI: -9.69, -1.99, p=0.003). Impaired LVEF (WMD=-2.24, 95% CI: -3.32, -1.17, p<0.001) was observed in the CM group. CONCLUSION: Statistical differences can be observed in some CMRI parameters between patients with myocarditis and healthy controls; however, apart from native T1 mapping, there were no large differences in other parameters between two groups, which may reveal the limited benefit of CMRI in assessing myocarditis in children and adolescents.


Asunto(s)
Miocarditis , Humanos , Niño , Adolescente , Miocarditis/diagnóstico por imagen , Medios de Contraste , Enfermedad Aguda , Gadolinio , Imagen por Resonancia Magnética/métodos , Valor Predictivo de las Pruebas
15.
J Endocrinol Invest ; 46(9): 1843-1854, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37020103

RESUMEN

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a subtype of nonfunctioning pituitary adenomas that exhibit more aggressive behavior. However, rapid and accurate preoperative diagnostic methods are currently lacking. DESIGN: The purpose of this study was to examine the differences between SCA and non-SCA features and to establish radiomics models and a clinical scale for rapid and accurate prediction. METHODS: A total of 260 patients (72 SCAs vs. 188 NSCAs) with nonfunctioning adenomas from Peking Union Medical College Hospital were enrolled in the study as the internal dataset. Thirty-five patients (6 SCAs vs. 29 NSCAs) from Fuzhou General Hospital were enrolled as the external dataset. Radiomics models and an SCA scale to preoperatively diagnose SCAs were established based on MR images and clinical features. RESULTS: There were more female patients (internal dataset: p < 0.001; external dataset: p = 0.028) and more multiple microcystic changes (internal dataset: p < 0.001; external dataset: p = 0.012) in the SCA group. MRI showed more invasiveness (higher Knosp grades, p ≤ 0.001). The radiomics model achieved AUCs of 0.931 and 0.937 in the internal and external datasets, respectively. The clinical scale achieved an AUC of 0.877 and a sensitivity of 0.952 in the internal dataset and an AUC of 0.899 and a sensitivity of 1.0 in the external dataset. CONCLUSIONS: Based on clinical information and imaging characteristics, the constructed radiomics model achieved high preoperative diagnostic ability. The SCA scale achieved the purpose of rapidity and practicality while ensuring sensitivity, which is conducive to simplifying clinical work.


Asunto(s)
Adenoma Hipofisario Secretor de ACTH , Adenoma , Neoplasias Hipofisarias , Humanos , Femenino , Adenoma Hipofisario Secretor de ACTH/cirugía , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Imagen por Resonancia Magnética , Estudios Retrospectivos
16.
BMC Ophthalmol ; 23(1): 260, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37303040

RESUMEN

BACKGROUND: Pure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves. Case presentation This report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations-namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium-in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations. CONCLUSION: Prominent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum's disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.


Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2b , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Párpados , Cara , Mutación , Fenotipo
17.
Public Health ; 223: 217-222, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37677851

RESUMEN

OBJECTIVES: We examined disparities in vaccine misinformation exposure and endorsement and the associations with vaccine hesitancy and vaccination uptake. STUDY DESIGN: Population-based survey. METHODS: A population-based survey was conducted on 5,002 Hong Kong adults oversampling low socio-economic status (SES, n = 2,200). Information on exposure (13 misinformation statements, total 0-13, median = 2), endorsement (13 statements, score 0-10, high scores indicate higher levels of endorsement, median = 5.75) of misinformation, vaccine hesitancy (14 items, score 1-5), and vaccination (two doses) were collected. Multivariable regression (adjusted ß [aß]) and Poisson regression (adjusted risk ratio [aRR]) adjusting for demographic characteristics were used to examine the associations of exposure to and endorsement of misinformation with vaccine hesitancy and vaccination. RESULTS: A total of 71.8% of respondents had at least exposure to one vaccine misinformation, and 35.7% had a high level of endorsement (median or above). Respondents with lower SES had a lower exposure (≤2 statements, 57.1% vs 50.1%, P < 0.001) but a higher level of endorsement (36.6% vs 34.9%, P = 0.01) of misinformation. Overall, 72.9% had been vaccinated for two or more doses, with a lower proportion in respondents with lower SES (83.6% vs 61.1%; P < 0.001). Compared with no exposure to misinformation, high levels of exposure and endorsement were associated with vaccine hesitancy (aß = 0.44, 95% confidence interval 0.40-0.48; aß = 0.50, 0.47-0.54, respectively) and lower vaccination rates (aRR = 0.98, 0.97-0.99; aRR = 0.92, 0.88-0.96, respectively). Vaccine hesitancy mediated the associations of exposure (fully, 100%) and endorsement (partially, 73%) with vaccination uptake. CONCLUSION: Endorsement of vaccine misinformation in respondents with lower SES was associated with low vaccination uptake.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Vacilación a la Vacunación , Vacunación , Clase Social , Comunicación
18.
Tech Coloproctol ; 27(12): 1155-1167, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37474693

RESUMEN

PURPOSE: The aim of the study was to evaluate the ability of magnifying chromoendoscopy (MCE) to correctly differentiate early colorectal cancer (CRC) lesions with massively invasive submucosal cancer (SMm) from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, slightly invasive submucosal cancer (SMs)). METHODS: We searched PubMed, Embase, the Cochrane Library from the time of the establishment of each database to 5 April 2023. Stata 15 software was used to perform the meta-analysis for sensitivity, specificity, positive likelihood ratio (LR), and negative LR, diagnostic odds ratio, and 95% CI. A summary receiver-operating characteristic (SROC) curve was constructed, the area under the curve (AUC) was calculated, and the diagnostic value was evaluated. Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the influencing factors of these studies and their impact on the diagnostic accuracy. MCE was used to evaluate the diagnostic accuracy in differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs). Subgroup analysis was conducted as well. Deeks' funnel plots were also used to assess publication bias. RESULTS: A total of 11,387 colorectal lesions were included in 19 articles, including polyp, adenoma, dysplasia, and early cancer (intramucosal cancer, SMs, and SMm). The aggregate sensitivity, specificity, positive LR, negative LR, and diagnostic advantage scores of MCE in the diagnosis of differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) were 0.78 (95% CI 0.72-0.83), 0.95 (0.95% CI 0.91-0.97), 15.4 (0.95% CI 8.7-27.4), 0.23 (0.95% CI 0.18-0.30), and 66 (0.95% CI 32-136), respectively. The AUC of the SROC curve was 0.91 (0.95% CI 0.88-0.93). No significant publication bias was found with Deeks' funnel plot. The results showed significant heterogeneity due to the different objects included. CONCLUSION: MCE can differentiate CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) with high accuracy and it can guide assessment of invasion depth of SMm in T1 early CRCs to help us select the most appropriate treatment.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Endoscopía , Adenoma/diagnóstico , Sensibilidad y Especificidad
19.
Zhonghua Nei Ke Za Zhi ; 62(7): 819-825, 2023 Jul 01.
Artículo en Zh | MEDLINE | ID: mdl-37394852

RESUMEN

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Mieloma Múltiple , Estomatitis , Masculino , Humanos , Femenino , Mieloma Múltiple/terapia , Mieloma Múltiple/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos , Creatinina , Movilización de Célula Madre Hematopoyética , Trasplante Autólogo , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Heterocíclicos/uso terapéutico , Bortezomib/uso terapéutico , Ciclofosfamida/uso terapéutico , Estomatitis/tratamiento farmacológico , Estomatitis/etiología
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(1): 186-189, 2023 Feb 18.
Artículo en Zh | MEDLINE | ID: mdl-36718710

RESUMEN

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.


Asunto(s)
Hipopotasemia , Indapamida , Humanos , Anciano , Hipopotasemia/inducido químicamente , Hipopotasemia/complicaciones , Indapamida/efectos adversos , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/terapia , Diuréticos/efectos adversos , Potasio , Electrólitos/efectos adversos , Anestesia General/efectos adversos
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