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PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.
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To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage â ¢ to â £. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.
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Perforación Intestinal , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Lactante , Pronóstico , Perforación Intestinal/etiología , Linfoma de Células B , Linfoma de Burkitt , Tracto Gastrointestinal , Linfoma no Hodgkin , Linfoma de Células B Grandes DifusoRESUMEN
Surgical navigation, despite its potential benefits, faces challenges in widespread adoption in clinical practice. Possible reasons include the high cost, increased surgery time, attention shifts during surgery, and the mental task of mapping from the monitor to the patient. To address these challenges, a portable, all-in-one surgical navigation system using augmented reality (AR) was developed, and its feasibility and accuracy were investigated. The system achieves AR visualization by capturing a live video stream of the actual surgical field using a visible light camera and merging it with preoperative virtual images. A skull model with reference spheres was used to evaluate the accuracy. After registration, virtual models were overlaid on the real skull model. The discrepancies between the centres of the real spheres and the virtual model were measured to assess the AR visualization accuracy. This AR surgical navigation system demonstrated precise AR visualization, with an overall overlap error of 0.53 ± 0.21 mm. By seamlessly integrating the preoperative virtual plan with the intraoperative field of view in a single view, this novel AR navigation system could provide a feasible solution for the use of AR visualization to guide the surgeon in performing the operation as planned.
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INTRODUCTION: Renal calculi are the predominant urological ailment in air force pilots. Flexible ureteroscopy (FURS) constitutes a valuable approach for renal calculi treatment. This study presents a decade-long exploration of using FURS for renal calculi treatment in air force pilots. Additionally, it investigates the safety and feasibility of granting waiver flights to pilots with renal parenchyma calcification. METHODS: From December 2009 to December 2019, a retrospective review was conducted on Chinese air force pilots undergoing treatment for renal calculi. Among the pilots assessed, a total of 71 individuals underwent FURS. Endoscopic methodology involved the insertion of a flexible ureteroscope into the ureter and renal pelvis, guided by a safety wire. Stone fragmentation was achieved using a holmium laser fibre, followed by extraction using a soft stone basket. Postoperative non-enhanced CT (NECT) scans was used to confirm stone clearance. Furthermore, clinical diagnoses were classified based on endoscopic findings and postoperative NECT results. All data were presented as mean (SD) or median (minimum-maximum) for continuous variables and frequency counts and percentages for categorical variables. RESULTS: FURS identified free kidney stones in 60 cases among all patients. The remaining 11 cases, without free stones detected during ureteroscopy, exhibited persistent high-density spots on postoperative NECT. Of the 60 cases with stones, renal calculi were successfully cleared in 30 pilots, while the remaining 30 exhibited persistent high-density spots on NECT postsurgery. Pilots with completely cleared free stones were deemed fit for flight. Pilots with diagnosed renal parenchyma calcification were granted permission to fly under waivers following a meticulous evaluation. CONCLUSIONS: FURS could not only effectively eliminate renal calculi but also accurately diagnose renal parenchyma calcification, facilitating a prompt return to flight for pilots. A protocol for managing pilot renal calculi, informed by FURS and our experience, is proposed.
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This retrospective study aimed to compare the accuracy of patient-specific implants (PSI) versus mandible-first computer-aided design and manufacturing (CAD/CAM) splints for maxilla repositioning in orthognathic surgery of skeletal Class II malocclusion patients. The main predictor was the surgical method (PSI vs. splints), with the primary outcome being the discrepancy in maxilla centroid position, and secondary outcomes being translation and orientation discrepancies. A total of 82 patients were enrolled (70 female, 12 male; mean age 25.5 years), 41 in each group. The PSI group exhibited a median maxillary position discrepancy of 1.25 mm (interquartile range (IQR) 1.03 mm), significantly lower than the splint group's 1.98 mm (IQR 1.64 mm) (P < 0.001). In the PSI group, the largest median translation discrepancy was 0.74 mm (IQR 1.17 mm) in the anteroposterior direction, while the largest orientation discrepancy was 1.83° (IQR 1.63°) in pitch. In the splint group, the largest median translation discrepancy was 1.14 mm (IQR 1.37 mm) in the anteroposterior direction, while the largest orientation discrepancy was 3.03° (IQR 2.11°) in pitch. In conclusion, among patients with skeletal Class II malocclusion, the application of PSI in orthognathic surgery yielded increased precision in maxillary positioning compared to mandible-first CAD/CAM splints.
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Objective: To assess the risk factors affecting development of non-tumor- related anastomotic stenosis after rectal cancer and to construct a nomogram prediction model. Methods: This was a retrospective study of data of patients who had undergone excision with one-stage intestinal anastomosis for rectal cancer between January 2003 and September 2018 in Nanfang Hospital of Southern Medical University. The exclusion criteria were as follows: (1) pathological examination of the operative specimen revealed residual tumor on the incision margin of the anastomosis; (2) pathological examination of postoperative colonoscopy specimens revealed tumor recurrence at the anastomotic stenosis, or postoperative imaging evaluation and tumor marker monitoring indicated tumor recurrence; (3) follow-up time <3 months; and (4) simultaneous multiple primary cancers. Univariate analysis using the χ2 or Fisher's exact test was performed to assess the study patients' baseline characteristics and variables such as tumor-related factors and surgical approach (P<0.05). Multivariate analysis using binary logistic regression was then performed to identify independent risk factors for development of non-tumor-related anastomotic stenosis after rectal cancer. Finally, a nomogram model for predicting non-tumor-related anastomotic stenosis after rectal cancer surgery was constructed using R software. The reliability and accuracy of this prediction model was evaluated using internal validation and calculation of the area under the curve of the model's receiver characteristic curve (ROC). Results: The study cohort comprised 1,610 patients, including 1,008 men and 602 women of median age 59 (50, 67) years and median body mass index 22.4 (20.2, 24.5) kg/m². Non-tumor-related anastomotic stenosis developed in 121 (7.5%) of these patients. The incidence of non-tumor-related anastomotic stenosis in patients who had undergone neoadjuvant chemotherapy, neoadjuvant radiotherapy, and surgery alone was 11.2% (10/89), 26.4% (47/178), and 4.8% (64/1,343), respectively. Neoadjuvant treatment (neoadjuvant chemotherapy: OR=2.455, 95%CI: 1.148-5.253, P=0.021; neoadjuvant chemoradiotherapy, OR=3.882, 95%CI: 2.425-6.216, P<0.001), anastomotic leakage (OR=7.960, 95%CI: 4.550-13.926, P<0.001), open laparotomy (OR=3.412, 95%CI: 1.772-6.571, P<0.001), and tumor location (distance of tumor from the anal verge 5-10 cm: OR=2.381, 95%CI:1.227-4.691, P<0.001; distance of tumor from the anal verge <5 cm: OR=5.985,95% CI: 3.039-11.787, P<0.001) were identified as independent risk factors for non-tumor-related anastomotic stenosis. Thereafter, a nomogram prediction model incorporating the four identified risk factors for development of anastomotic stenosis after rectal cancer was developed. The area under the curve of the model ROC was 0.815 (0.773-0.857, P<0.001), and the C-index of the predictive model was 0.815, indicating that the model's calibration curve fitted well with the ideal curve. Conclusion: Non-tumor-related anastomotic stenosis after rectal cancer surgery is significantly associated with neoadjuvant treatment, anastomotic leakage, surgical procedure, and tumor location. A nomogram based on these four factors demonstrated good discrimination and calibration, and would therefore be useful for screening individuals at risk of anastomotic stenosis after rectal cancer surgery.
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Anastomosis Quirúrgica , Nomogramas , Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Constricción Patológica/etiología , Factores de Riesgo , Análisis Multivariante , Anciano , Complicaciones Posoperatorias/etiología , Recurrencia Local de Neoplasia , Modelos LogísticosRESUMEN
OBJECTIVE: To develop the'E-Bone', a comprehensive one-stop preoperative planning system for reverse total shoulder arthroplasty with improved accuracy and efficiency. METHODS: The nnU-net deep neural network was utilized for scapula segmentation to obtain precise scapula segmentation results. Based on the 3 key factors, namely bone density, upward and downward angle and nail length, the base was automatically positioned. The quantitative parameters required for surgical planning were calculated. A personalized guide plate was generated by combining glenoid morphology and base positioning information. The system interface was developed to modularize various functions for easy use, providing interactive operation and real-time display. RESULTS: Compared with the Mimics system, the'E-bone'preoperative planning system reduced complex manual adjustments during the planning process. The average planned nail length was longer than that of the Mimics system, and the planning time was reduced by 86%. The scapula segmentation accuracy of this system reached 99.93%, better than that of Mimics to achieve a higher precision. CONCLUSION: The"E-bone"system provides a one-stop, efficient, and accurate preoperative planning system for reverse shoulder replacement and potentially broader clinical applications.
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Artroplastía de Reemplazo de Hombro , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Redes Neurales de la Computación , Escápula/cirugía , Cirugía Asistida por Computador/métodosRESUMEN
BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.
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Apolipoproteína E4 , Disfunción Cognitiva , Conducta Sedentaria , Humanos , Disfunción Cognitiva/genética , Disfunción Cognitiva/epidemiología , Femenino , Masculino , Apolipoproteína E4/genética , Estudios Prospectivos , Anciano , Factores de Riesgo , Estudios Longitudinales , Persona de Mediana Edad , Ejercicio Físico , China/epidemiologíaRESUMEN
Objective: To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods: This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity. Results: Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment. Conclusions: Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.
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Subfamilia B de Transportador de Casetes de Unión a ATP/deficiencia , Colestasis Intrahepática , Secuenciación del Exoma , Humanos , Masculino , Femenino , Colestasis Intrahepática/genética , Colestasis Intrahepática/diagnóstico , Estudios Retrospectivos , Niño , Preescolar , Lactante , Adolescente , Mutación , Hígado/patología , gamma-Glutamiltransferasa/sangre , Alanina Transaminasa/sangre , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Pronóstico , Aspartato Aminotransferasas/sangreRESUMEN
Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.
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Cuello del Útero , Sensibilidad y Especificidad , Tomografía de Coherencia Óptica , Neoplasias del Cuello Uterino , Humanos , Femenino , Tomografía de Coherencia Óptica/métodos , Adulto , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Persona de Mediana Edad , Cuello del Útero/diagnóstico por imagen , Cuello del Útero/patología , Adolescente , Anciano , Displasia del Cuello del Útero/diagnóstico por imagen , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Adulto Joven , Frotis Vaginal , Biopsia , Valor Predictivo de las Pruebas , Detección Precoz del Cáncer/métodosRESUMEN
BACKGROUND: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. METHODS: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. RESULTS: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19 + MIF + epithelial cells and via epithelial-stromal crosstalk. CONCLUSIONS: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
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Células Epiteliales , Fibrosis de la Submucosa Bucal , Humanos , Fibrosis de la Submucosa Bucal/patología , Fibrosis de la Submucosa Bucal/metabolismo , Animales , Células Epiteliales/metabolismo , Linfocitos T/metabolismo , Linfocitos T/inmunología , Ratas , Células Madre/metabolismo , Células Madre/citología , Masculino , Mucosa Bucal/patología , Mucosa Bucal/metabolismo , Comunicación CelularRESUMEN
Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed. Results: â 326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS â ¡ patients. The median progression-free survival (PFS) time of R2-ISS â , R2-ISS â ¡, R2-ISS â ¢, and R2-ISS â £ was 52, 29, 20, and 15 months (P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months (P<0.001). Multifactor analysis revealed that ISS â ¡, ISS â ¢, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS â ¡, ISS â ¢, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. â¡The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. â¢The median PFS for 1q+-related double-hit in R2-ISS â ¢ and â £ were 20, 15 months (P=0.084) and the median OS were 35, 36 months (P=0.786), respectively. In R2-ISS â ¢, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months (P=0.974), while the median OS was 35, 47, and 56 months (P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping (P<0.001) . Conclusions: The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS â ¡ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.
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Mieloma Múltiple , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Pronóstico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Estudios Retrospectivos , Aberraciones Cromosómicas , Análisis de Supervivencia , Estadificación de NeoplasiasRESUMEN
Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder characterized by high heterogeneity. This study aimed to further understand the correlation between clinical phenotypes and genotypes in GD patients through a retrospective analysis of 20 cases in Shanxi Bethune Hospital, including their clinical manifestations, laboratory tests, enzyme studies, and genetic results. Among the 20 GD patients, 16 were classified as Type â GD with a median age of diagnosis of 24 years, and 4 were classified as Type â ¢ GD with a median age of diagnosis of 19 years. All patients exhibited splenomegaly and thrombocytopenia, with 16 patients showing skeletal imaging changes, and 5 of them presenting with bone pain symptoms. Genetic analysis revealed 15 distinct mutations, predominantly missense mutations, with L483P being the most prevalent (35.7%), followed by V414L, L303I, and F252I. Mutation sites were predominantly located in exon 7. Noteworthy findings included the first report of the S310G mutation by our research group and the first occurrence of the K196R mutation in the Chinese population. Additionally, the N227S mutation was implicated in a potential association with neuropathy. Despite advancements, Uncertainties still exist in the correlation between clinical phenotypes and genotypes in GD patients.
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Enfermedad de Gaucher , Humanos , Adulto Joven , Adulto , Enfermedad de Gaucher/genética , Estudios Retrospectivos , Fenotipo , Genotipo , MutaciónRESUMEN
Numerous organic molecules are known to inhibit the main protease (MPro) of SARS-CoV-2, the pathogen of Coronavirus Disease 2019 (COVID-19). Guided by previous research on zinc-ligand inhibitors of MPro and zinc-dependent histone deacetylases (HDACs), we identified BRD4354 as a potent inhibitor of MPro. The in vitro protease activity assays show that BRD4354 displays time-dependent inhibition against MPro with an IC50 (concentration that inhibits activity by 50%) of 0.72 ± 0.04 µM after 60 min of incubation. Inactivation follows a two-step process with an initial rapid binding step with a KI of 1.9 ± 0.5 µM followed by a second slow inactivation step, kinact,max of 0.040 ± 0.002 min-1. Native mass spectrometry studies indicate that a covalent intermediate is formed where the ortho-quinone methide fragment of BRD4354 forms a covalent bond with the catalytic cysteine C145 of MPro. Based on these data, a Michael-addition reaction mechanism between MPro C145 and BRD4354 was proposed. These results suggest that both preclinical testing of BRD4354 and structure-activity relationship studies based on BRD4354 are warranted to develop more effective anti-COVID therapeutics.
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For most patients undergoing clear aligner treatment, it could be necessary to bond multiple attachments on their tooth surfaces. The clear aligner attachment is designed to enhance aligner retention, transmit orthodontic forces, and make the programmed tooth movement more predictable. Materials such as restorative resin, orthodontic bonding adhesive, flowable resin, and resin-modified glass ionomer cement are currently used for attachment bonding. But there is currently no conclusion as to which material suits most. The objective of this review is to look into the studies published in recent years, in order to explore the optimal material option for making clear aligner attachments.
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Recubrimiento Dental Adhesivo , Aparatos Ortodóncicos Removibles , Humanos , Ensayo de Materiales , Cementos de Ionómero Vítreo , Cementos de Resina , Resinas CompuestasRESUMEN
BACKGROUND: The incidence of preserved ejection fraction heart failure has significantly increased in persons with type 2 diabetes mellitus (T2DM). Left ventricular (LV) diastolic dysfunction is an early and important manifestation of preserved ejection fraction heart failure. The onset of heart failure in persons with diabetes is associated with diabetic neuropathy. However, the relationship among sudomotor function, which is an early manifestation of small fiber neuropathy, and LV diastolic function remains unclear. This study aimed to explore the association between sudomotor function and LV diastolic function in persons with T2DM. METHODS: In total, 699 persons with T2DM were enrolled and divided into three groups according to electrochemical skin conductance (ESC) assessed using the SUDOSCAN device: "no dysfunction" group (NSF), "moderate dysfunction" group (MDF), and "severe dysfunction" group (SDF). LV diastolic function was assessed using Doppler echocardiography. To evaluate the relationship between ESC and echocardiographic parameters, Pearson's correlation analysis was performed. Additionally, logistic regression analysis was used to determine the association between LV diastolic function and ESC. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of sudomotor function indicators in detecting impaired cardiac diastolic function. RESULTS: There were 301 persons (43.06%) in the NSF group, 232 (33.19%) in the MDF group, and 166 (23.75%) in the SDF group. Compared to the NSF group, the MDF and SDF groups had higher A and E/e' and lower e' values (all p < 0.05). Pearson's correlation analysis showed that A and E/e' were negatively associated with foot ESC (FESC) and hand ESC (HESC), whereas e' was positively associated with FESC and HESC (all p < 0.05). After adjusting for confounding factors, binary logistic regression analysis showed that ESC was independently associated with impaired LV diastolic function (p = 0.003). The area under the ROC curve values for FESC and HESC were 0.621 and 0.635, respectively (both p < 0.05). CONCLUSIONS: Deteriorating sudomotor function was associated with reduced diastolic function indicators. ESC can be used as a biomarker for detecting LV diastolic impairment.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Función Ventricular Izquierda , Disfunción Ventricular Izquierda/diagnóstico , Insuficiencia Cardíaca/complicacionesRESUMEN
The development of preeclampsia (PE) is associated with the impaired trophoblast motility. MicroRNAs (miRs) contribute to the modulation of trophoblast invasion. In the current study, the role of miR-206/AGTR1 in the TNF-alpha-induced invasion defect of trophoblasts was explored. The levels of miR-206 and ATGR1 in clinical placenta tissues were investigated. Trophoblasts were treated with TNF-alpha, and the levels of miR-206 and ATGR1 were modulated. Changes in cell viability, invasion, and inflammation in trophoblasts were detected. The level of miR-206 was induced, while the level of AGTR1 was suppressed in placenta tissues. In in vitro assays, TNF-alpha suppressed viability, induced inflammatory response, inhibited invasion, upregulated miR-206, and down-regulated AGTR1. The inhibited expression of miR-206 or the overexpression of AGTR1 counteracted the effects of TNF-alpha, indicating the key role of the miR-206/AGTR1 in progression of PE. Collectively, miR-206 suppressed viability, induced inflammatory response, and decreased invasion of trophoblasts by inhibiting AGTR1.
Asunto(s)
MicroARNs , Preeclampsia , Embarazo , Femenino , Humanos , Placenta/metabolismo , Preeclampsia/genética , Preeclampsia/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Trofoblastos/metabolismo , Movimiento Celular , Proliferación Celular , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismoRESUMEN
OBJECTIVE: This study aimed to analyze the maternal and fetal outcomes of pregnant women with pre-eclampsia (PE), complicated with fetal growth restriction (FGR), and establish a prediction model of vaginal delivery to guide the selection of the delivery mode. PATIENTS AND METHODS: The study included 208 pregnant women with PE complicated with FGR. Of them, 49 patients were in the vaginal delivery group, and 159 patients were in the cesarean section group. The relevant maternal and fetal outcomes were analyzed. Patients were randomly divided into the training sample group and the test group with a ratio of 2:1. The three-layer neural network was used to select 24 maternal and infant outcome factors as the input nodes of the neural network to build a vaginal delivery prediction model. RESULTS: Results showed that the gestational age, the highest systolic and diastolic blood pressure, body weight, body length, and placental weight of the newborns in the vaginal delivery group were significantly higher than those in the cesarean section group. Incidence of preterm birth, amniotic fluid grade III, oligohydramnios, and severe small-for-gestational-age (sSGA) neonates were significantly lower in the vaginal delivery group compared to the cesarean section group (p < 0.05). A three-layer neural network delivery prediction model was constructed, and the accuracy rate of fitting with test samples was 91.80%. CONCLUSIONS: There is no significant difference in the incidence of maternal and fetal complications in PE complicated with FGR in different delivery methods. The three-layer neural network prediction model has good prediction ability for vaginal delivery of PE complicated with FGR and may be applied in clinical practice.
Asunto(s)
Preeclampsia , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Retardo del Crecimiento Fetal/etiología , Cesárea/efectos adversos , Mujeres Embarazadas , Placenta , Parto Obstétrico/efectos adversosRESUMEN
This study used machine learning techniques combined with routine blood cell analysis parameters to build preliminary prediction models, helping differentiate patients with depression from healthy controls, or patients with anxiety. A multicenter study was performed by collecting blood cell analysis data of Beijing Chaoyang Hospital and the First Hospital of Hebei Medical University from 2020 to 2021. Machine learning techniques, including support vector machine, decision tree, naïve Bayes, random forest and multi-layer perceptron were explored to establish a prediction model of depression. The results showed that based on the blood cell analysis results of healthy controls and depression group, the accuracy of prediction model reached as high as 0.99, F1 was 0.975. Receiver operating characteristic curve area and average accuracy were 0.985 and 0.967, respectively. Platelet parameters contributed mostly to depression prediction model. While, to random forest differential diagnosis model based on the data from depression and anxiety groups, prediction accuracy reached 0.68 and AUC 0.622. Age, platelet parameters, and average volume of red blood cells contributed the most to the model. In conclusion, the study researched on the prediction model of depression by exploring blood cell analysis parameters, revealing that machine learning models were more objective in the evaluation of mental illness.
Asunto(s)
Depresión , Aprendizaje Automático , Humanos , Teorema de Bayes , Máquina de Vectores de Soporte , Recuento de Células SanguíneasRESUMEN
Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.