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OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.
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BACKGROUND: Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders of varying severity characterized by bone fragility. The primary objective of this international multidisciplinary collaboration initiative was to reach a consensus for a standardized set of clinician and patient-reported outcome measures, as well as associated measuring instruments for dental care of individuals with OI, based on the aspects considered important by both experts and patients. This project is a subsequent to the Key4OI project initiated by the Care4BrittleBones foundation which aims to develop a standard set of outcome measures covering a large domain of factors affecting quality of life for people with OI. An international team of experts comprising orthodontists, pediatric dentists, oral and maxillofacial surgeons, and prosthetic dentists used a modified Delphi consensus process to select clinician-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs) to evaluate oral health in individuals with OI. Important domains were identified through a literature review and by professional expertise (both CROMs and PROMs). In three focus groups of individuals with OI, important and relevant issues regarding dental health were identified. The input from the focus groups was used as the basis for the final set of outcome measures: the selected issues were attributed to relevant CROMs and, when appropriate, matched with validated questionnaires to establish the final PROMs which represented best the specific oral health-related concerns of individuals with OI. RESULTS: Consensus was reached on selected CROMs and PROMs for a standard set of outcome measures and measuring instruments of oral health in individuals with OI. CONCLUSIONS: Our project resulted in consensus statements for standardization oral health PROMs and CROMs in individuals with OI. This outcome set can improve the standard of care by incorporating recommendations of professionals involved in dental care of individuals with OI. Further, it can facilitate research and international research co-operation. In addition, the significant contribution of the focus groups highlights the relevance of dental and oral health-related problems of individuals with OI.
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Salud Bucal , Osteogénesis Imperfecta , Humanos , Salud Bucal/normas , Calidad de Vida , Evaluación de Resultado en la Atención de Salud , Masculino , Femenino , Medición de Resultados Informados por el PacienteRESUMEN
Objective: To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma. Methods: A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results: The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant(Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion: Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.
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Neoplasias de Cabeza y Cuello , Ganglios Linfáticos , Metástasis Linfática , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Persona de Mediana Edad , Masculino , Anciano , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Ganglios Linfáticos/patología , Arterias Carótidas/cirugía , Cuello , Calidad de Vida , Recurrencia Local de Neoplasia , Femenino , StentsRESUMEN
Objective: To evaluate the clinical efficacy of transoral robotic surgery (TORS) with the da Vinci robot system in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Methods: A mixed cohort study was conducted to collect and analyze the clinical data of OPSCC patients who underwent TORS at the Eye & ENT Hospital, Fudan University between July 2020 and February 2023 (TORS group). OPSCC patients who underwent conventional surgery between January 2016 and September 2020 were included as the control group. The baseline information, incidence of complications and follow-up data were compared between the two groups. Results: A total of 166 patients were included, with 102 cases (81 males and 21 females) in the TORS group [mean age: (59.1±9.8) years] and 64 cases (54 males and 10 females) in the control group [ mean age: (57.6±9.7) years]. Compared with the control group, the TORS group had lower postoperative bleeding rate [2.9% (3/102) vs 10.9% (7/64), P=0.035] and infection rate [1.0% (1/102) vs 18.8% (12/64), P<0.001]. No statistically significant differences were observed in tracheotomy rate [46.1% (47/102) vs 59.4% (38/64), P=0.070] and median length of hospital stay [8 (7, 10) d vs 10 (4, 12) d, P=0.088]. After propensity score matching, compared with the control group, the TORS group had lower postoperative infection rate [0 (0/31) vs 19.4% (6/31), P=0.032] and median length of hospital stay [7 (7, 10) d vs 10 (8, 12) d, P=0.031]. No statistically significant differences were found in postoperative bleeding rate [3.2% (1/31) vs 6.5% (2/31), P=1.000] and tracheotomy rate [22.6% (7/31) vs 45.2% (14/31), P=0.060] between the two groups. Moreover, 1-and 2-year disease-free survival rates were 96.3% and 94.6% in the TORS group, and 90.6% and 84.3% in the control group, respectively (P=0.233). The 1-and 2-year cancer-specific survival rates were both 100% in the TORS group, and 96.9% and 93.8% in the control group, respectively (P=0.539). Conclusion: TORS for OPSCC is associated with high clinical safety and favorable oncological outcomes.
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Neoplasias Orofaríngeas , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Orofaríngeas/cirugía , Carcinoma de Células Escamosas/cirugía , Resultado del Tratamiento , Estudios de Cohortes , Complicaciones Posoperatorias , Tiempo de Internación , Anciano , Hemorragia PosoperatoriaAsunto(s)
Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Humanos , Femenino , Terapia de Reemplazo Enzimático/métodos , alfa-Glucosidasas/uso terapéutico , alfa-Glucosidasas/genética , MutaciónRESUMEN
Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p (r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 (r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p (r=-0.394, Pï¼0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G0/G1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased (Pï¼0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm3 vs (857±114) mm3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, Pï¼0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.
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Proliferación Celular , Ratones Desnudos , MicroARNs , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Animales , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Ratones , Línea Celular Tumoral , Apoptosis , ARN Circular/metabolismo , ARN Circular/genética , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ciclo Celular , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
This work presents the changing abundance of surface functional groups (SFGs) on polystyrene (PS) upon weathering within one or a few molecular monolayers from a molecular point of view. PS particles were aged by exposing it to a gas flow of typically (5 %) O3 in O2 (PSO3), UV radiation using a solar simulator under controlled conditions in the laboratory (PSSS) and to the water/air interface immerged in a freshwater lake for 2 months (PSL). The chemical composition of the interface of weathered, compared to pristine (virgin or PSV) material was established using a titration technique that probed the chemical composition of the molecular interface of the polymer. The main conclusions of this exploratory study are: (a) The interface of PS changes significantly compared to ATR-FTIR spectra that do not show additional absorptions in the mid-IR spectrum over a penetration depth of more than hundred monolayers at 10 µm; (b) The average surface functionalization of the gas-solid interface, corresponding to the sum of all examined types of SFG, increases from 20 % of a monolayer for PSV to 40, 50 and 84 % for PSL, PSO3 and PSSS, respectively; (c) in all cases the most important SFG was surface -OH ranging from 11.2 to 64 % for PSV and PSSS, respectively; (d) each PS sample shows a characteristic SFG pattern or fingerprint using several probe gases; (e) O3 interaction led to interface acidification; (f) UV treatment leads to the highest degree of surface -OH functionalization compared to PSO3 and PSL. The accumulation of SFG's renders the interface more reactive towards adsorption of probe gases.
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Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.
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Anticuerpos Monoclonales Humanizados , Arritmias Cardíacas , Infarto del Miocardio , Ratas Sprague-Dawley , Receptores de Interleucina-6 , Animales , Masculino , Infarto del Miocardio/complicaciones , Ratas , Arritmias Cardíacas/etiología , Receptores de Interleucina-6/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/farmacología , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Objective: To explore the operational accuracy and operative time of oral surgery robot-assisted endodontic microsurgery on a head-simulator for clinical reference. Methods: Three pairs of surgical simulation models were set up on head-simulator. Each model included 10 positions anteriorly and posteriorly, 20 teeth for each technique, for a total of 60 teeth. An attending physician with more than 3 years clinical experience in endodontic microsurgery completed fixed-point osteotomy and apicoectomy in three groups of endodontic microsurgery under freehand (FH), static navigation (SN), and surgery robot (SR). The duration of each operation was recorded. Cone-beam CT was taken before the operation and the surgical path was planned in the software; after surgery, a plug gauge (precision gauge for measuring hole dimensions) was inserted into the surgical path for intraoral scanning. Surgical accuracy (starting point, end point, and angular deviation) was assessed in all 3 groups, and surgery time was compared. Results: The deviation at the starting point and the end point, and angular deviation was (0.37±0.11), (0.37±0.10) mm, and 0.71°±0.17°in the SR group. The deviations in the SR group were significantly lower than those in the SN group [(0.59±0.14), (0.65±0.18) mm, and 2.64°±0.75°] (P<0.05), and both groups were significantly lower than the FH group [(1.37±0.31), (1.10±0.21) mm, and 9.84°±3.15°] (P<0.05). The operative time in the SN group [(1.20±0.03) min] was significantly less than that in the SR group [(2.18±0.03) min] (P<0.05), and both groups were significantly less than that in the FH group [(8.70±3.15) min] (P<0.05). Starting point deviation, end point deviation, and angular deviation [(1.09±0.10), (0.90±0.07) mm, 7.22°±1.13°] in anterior teeth using the FH was significantly lower than the starting deviation, endpoint deviation, and angular deviation [(1.65±0.14), (1.30±0.06) mm, 12.46°±2.10°] in the posterior teeth using FH (P<0.05), and the operative time in the anterior teeth using the FH [(5.75±0.57) min] was significantly less than that in the posterior teeth using [(11.65±1.14) min] (P<0.05). The difference in accuracy and operative time between using SN and SR on anterior and posterior teeth was not statistically significant (P>0.05). Conclusions: Oral surgery robot-assisted endodontic microsurgery helps improving the accuracy of clinicians' operations and shorten the operation time.
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Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43â. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.
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Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Mitomicina/administración & dosificación , Mitomicina/uso terapéutico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/terapiaRESUMEN
Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase â ¡ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hipofaríngeas , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/patología , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Cisplatino/administración & dosificación , Estudios Prospectivos , Quimioterapia de Inducción , Estudios de Cohortes , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Docetaxel/uso terapéutico , Docetaxel/administración & dosificación , Resultado del Tratamiento , AdultoRESUMEN
Standard treatment for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) whose larynx could not be preserved surgically consists mainly of concurrent chemoradiotherapy (CCRT). Induction chemotherapy (ICT) followed by radiotherapy or chemoradiotherapy is also an alternative option. However, whether ICT could provide survival benefits for patients with LAHNSCC, besides its role in laryngeal preservation and selecting the treatment modality, is still controversial. The article summarizes the current position of ICT for LAHNSCC and discusses the standard regimen of ICT, its role in larynx preservation, its ability to predicting the result of chemoradiotherapy, clinical outcomes regarding the survival benefits after ICT, its role in the treatment deintensification for human papillomavirus-positive LAHNSCC and its application in the era of immunotherapy.
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Carcinoma de Células Escamosas , Quimioradioterapia , Neoplasias de Cabeza y Cuello , Quimioterapia de Inducción , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamiento farmacológicoRESUMEN
Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 µmol/L, 20 µmol/L and 40 µmol/L hinokiol treatment groups, and 10 µg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G0/G1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G0/G1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.
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Apoptosis , Compuestos de Bifenilo , Ciclo Celular , Vía de Señalización Hippo , Lignanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Transducción de Señal , Humanos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Carcinoma Nasofaríngeo/metabolismo , Ciclo Celular/efectos de los fármacos , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Lignanos/farmacología , Compuestos de Bifenilo/farmacología , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAP , Proteínas Serina-Treonina Quinasas/metabolismo , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/metabolismoRESUMEN
Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
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Dasatinib , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , China , Dasatinib/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Pirimidinas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , /uso terapéuticoRESUMEN
Objective: To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures. Methods: From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method. Results: A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure (P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion: Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.
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Neumoconiosis , Humanos , Neumoconiosis/epidemiología , Neumoconiosis/economía , China/epidemiología , Masculino , Costo de Enfermedad , Soldadura , Años de Vida Ajustados por Discapacidad , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/economía , Femenino , Exposición Profesional , AdultoRESUMEN
Chronic kidney disease (CKD) is a major public health problem worldwide. When CKD patients progress to the stage of kidney failure, kidney replacement therapy (KRT) or conservative treatment (palliative or non-dialysis treatment) will be needed. The risk prediction models of chronic kidney failure have been developed in recent years. These models, focusing on demographic indicators, clinical indicators, and laboratory data, are used to predict the likelihood of progression to kidney failure and requiring KRT. This article will retrieve prediction models for chronic kidney failure as an outcome, demonstrate the current research progress, and hope that it may be helpful for the strategies of preventing chronic kidney failure.
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Fallo Renal Crónico , Humanos , Fallo Renal Crónico/terapia , Factores de Riesgo , Medición de Riesgo , Progresión de la EnfermedadRESUMEN
Objective: The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation. Methods: We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation. Results: A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence. Conclusion: Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.
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Mesenterio , Anomalía Torsional , Humanos , Mesenterio/cirugía , Anomalía Torsional/cirugía , Resultado del Tratamiento , Laparotomía , Recurrencia , Masculino , Femenino , Persona de Mediana Edad , AdultoRESUMEN
Objective: To deepen understanding of IgG4-related diseases (RDs), we analyzed the associated lymphocyte subtypes, and explored the pathogenesis and potential immunotherapeutic targets. Methods: Eighty-six patients with IgG4-RDs were enrolled, and their clinical characteristics, peripheral lymphocyte subtypes, and disease course were analyzed. Results: The mean age of the participants was 36-87(62±11) years; 51 were male (59.3%) and 35 were women (40.7%); and 34.9% had a history of allergy. Follow-up lasted 4.8 (0.4, 14.1) months. The most common symptoms were abdominal pain, and submandibular gland and lacrimal gland swelling (each 20.9%). Sixty-five (75.6%) participants had multiple organ involvement, and the most frequently affected organs were the pancreas (52.3%), submandibular gland (51.2%), and lacrimal gland (34.9%). A high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and low complement C3 and C4 concentrations were present in 18.8% (16/85), 30.0% (24/80), 72.9% (62/85), 58.3% (28/48), 89.5% (77/86), 61.2% (52/85), and 50.0% (42/84), respectively, of the participants. In addition, 64.7% (55/85) were positive for autoantibodies, and the most frequent was anti-nuclear antibody (63.5%). The proportion of CD4+T lymphocytes increased in 25.7% (9/35) of the participants, which was accompanied by an increase in the ratio of CD4+/CD8+T lymphocytes (22.9%, 8/35). Importantly, most participants (90.0%, 18/20) had a high proportion of regulatory T (Treg) cells. High interleukin (IL)-2, IL-6, and IL-10 concentrations were present in 50.0% (11/22), 33.3% (10/30), and 16.7% (5/30), respectively, of the participants. Substantial lymphoplasmacytic infiltration, fibrosis, IgG4-positive plasma cell infiltration, and lymphoid follicle hyperplasia or ectopic formation were present in 79.2% (42/53), 67.9%(36/53), 35.8%(19/53) and 30.2% (16/53), respectively, of the participants. Fifty-three participants with detailed pathologic data were also further evaluated, of whom 24.5% (13/53), 3.8% (2/53), and 67.9% (36/53) had definite, probable, and possible diagnoses; and 3.8% (2/53) could not be diagnosed. Compared with baseline, the percentage of eosinophils and the IgE, IgG, and IgG4 concentrations decreased significantly; and the complement C3 and C4 concentrations had increased significantly after 6 months of treatment (all P<0.05). The IgG4 concentration after 6 months of treatment negatively correlated with that of C4, and positively correlated with the baseline concentration of IgE and the IgG4/IgG ratio. Conclusion: IgG4-RDs are a group of diseases characterized by male predisposition; multiple organ involvement; a high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and a low C3 concentration. Peripheral CD4+T cells and Treg cells are also more abundant. The diseases can be controlled with glucocorticoids and immunosuppressive drugs in the majority of instances. The IgG4 concentration after 6 months of treatment negatively correlates with the baseline complement C4 concentration and positively correlates with the IgE concentration and IgG4/IgG ratio, which suggests that IgG4/IgG, IgE, and complement should be closely monitored to evaluate disease activity and the efficacy of treatment in such patients.