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Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4+, CD14+, CD68+, and FOXP3+ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.
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Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARalpha/CPT1alpha pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. Keywords: Obesity, Exercise, Diet, Mitochondrial function, Lipid deposition.
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Dieta Alta en Grasa , Entrenamiento de Intervalos de Alta Intensidad , Metabolismo de los Lípidos , Hígado , Obesidad , Ratas Sprague-Dawley , Animales , Obesidad/metabolismo , Obesidad/terapia , Masculino , Dieta Alta en Grasa/efectos adversos , Ratas , Hígado/metabolismo , Condicionamiento Físico Animal/fisiologíaRESUMEN
This study aims at examining the application and development of digital teaching materials in the field of epidemiology, encompassing both China and international contexts. The research involved conducting search on websites and literature databases to assess the status of digital teaching materials in epidemiology, nationally and internationally. At present, in China, digital teaching materials used in epidemiology are primarily presented in the form of printed books with added QR codes, providing teaching resources such as videos and exercises. However, issues with the level of interactivity have been identified. In foreign countries, with stronger emphasis placed on personalization, interactivity, and the use of rich media technologies in the digital teaching materials, epidemiologically. Enhanced digitization regarding materials and learning outcomes is achieved through features such as real-time notes, interactive animations, and quizzes. These approaches are considered worth considering for adoption. This study provides valuable insights for the digital transformation of epidemiology education.
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Epidemiología , Materiales de Enseñanza , Enseñanza , Epidemiología/educación , China/epidemiología , HumanosRESUMEN
Objective: To explore the differences in the performance and tissue repair promotion effects of small intestinal submucosa membrane (SIS membrane) and Bio-Gide resorbable collagen membrane (Bio-Gide membrane) by performing the subcutaneous implantation models in mice. Methods: For in vivo studies, we stablished membrane implantation models using 6-8 week-old male C57BL/6 mice. The degradation rates were explored through HE staining analysis at different time points (1, 3, 5, 7, 14 and 28 d, 3 mice/group/time point). The influences of the two membranes on local macrophages and neovasculum were evaluated by immunofluorescence detection of F4/80 and CD31, and the mobilization effects of the two membranes on local stem cells were evaluated by immunohistochemical detection of Ki67 and CD146. For in vitro studies, mice periodontal ligament stem cells (mPDLSCs) were co-cultured with these two membrane materials, and the cell morphologies were observed by scanning electron microscopy. In addition, the gene expressions of Ki67, Cxcl1, Ccl1, Tnfa were investigated by real-time fluorescence quantitative PCR (RT-qPCR). Results: The results of in vivo studies showed that by day 28, there was no significant difference in degradation rate between these two membrane materials [SIS degradation rate: (16.84±4.00) %, Bio-Gide degradation rate: (24.07±3.97) %, P=0.090], illustrating that both of them could maintain the barrier effects for more than one month. In addition, there was no significant difference in the infiltration number of local F4/80 positive macrophages between these two groups by the day 3 after implantation [SIS: (20.67±5.69) cells/visual field, Bio-Gide: (25.33±2.52) cells/visual field, P=0.292]. However, compared with the Bio-Gide membrane, SIS membrane significantly promoted local CD31+vascular regeneration [SIS: (4.67±1.15) cells/visual field, Bio-Gide: (1.00±1.00) cells/visual field, P=0.015] and CD146+stem cell recruitment [SIS: (22.33±4.16) cells/visual field, Bio-Gide: (11.33±2.52) cells/visual field, P=0.025]. The RT-qPCR results also showed that SIS membrane promoted the gene expression of Cxcl1 (SIS vs Bio-Gide P<0.001) in mPDLSCs, but had no effect on the gene expression of Tnfa (SIS vs Bio-Gide P=0.885). Conclusions: SIS membrane showed a similar degradation rate compared with Bio-Gide membrane, and there was no significant difference in the effects of these two membranes on local inflammation or macrophages. Therefore, both of these membranes could meet the barrier effects required by guided tissue regeneration.
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Materiales Biocompatibles , Regeneración Ósea , Masculino , Ratones , Animales , Antígeno CD146/farmacología , Antígeno Ki-67 , Ratones Endogámicos C57BL , Colágeno , Membranas ArtificialesRESUMEN
Objective: To explore the preoperative whole perforator evaluation and intraoperative eccentric design of anterolateral thigh flap (ALTF) based on superficial fascial perforators by modified computed tomography angiography (CTA), and the clinical effects were observed. Methods: A prospective observational study was adopted. Twelve patients with oral and maxillofacial tumors and 10 patients with open injury of the upper limb with large soft tissue defects were hospitalized in the Department of Hand & Microsurgery and Department of Oral & Maxillofacial Surgery of Affiliated Hospital of Binzhou Medical University from January 2021 to July 2022, with 12 males and 10 females, aged from 33 to 75 years, an average age of 56.6 years. The wounds of the patients with oral and maxillofacial tumors were reconstructed by ALTF after the extensive tumor resection and radical cervical lymph node dissection in the same stage; the wounds of the patients with skin and soft tissue defect on the upper limb were covered by ALTF in stage â ¡ after debridement in stage â . After debridement, the area of wound was 3.5 cm×3.5 cm-25.0 cm×10.0 cm and the area of the required flap area was 4.0 cm×4.0 cm-23.0 cm×13.0 cm. Modified CTA scan was performed on the donor site of ALTF before the operation, with the parameters of modified CTA being set to mainly reduce the tube voltage and tube current, and increase the contrast dose and the dual phase scan. The acquired image data were sent to GE AW 4.7 workstation and adopted the volume reconstruction function for visual reconstruction and evaluation of the whole perforator. The information of perforator and source artery was marked on the body surface before operation according to the above evaluation. During the operation, an eccentric flap centered on the visible superficial fascia whole perforator was designed and cut according to the desired flap area and shape. The donor sites of the flap were repaired by direct sutures or full-thickness skin grafts. The total radiation dose was compared between the modified CTA scan and the traditional CTA scan. The distribution of outlet point of perforator of double thighs, the length and direction of superficial fascia perforators based modified CTA were recorded. The type, number, and origin of the target perforator, distribution of of outlet point of perforator, and the diameter, course, and branch of the source artery observed before the operation were compared with those observed during the operation. The healing of donor site wound and the survival of flaps in recipient site were observed after operation. The texture and appearance of flap, oral and upper limb functions, and the functions of femoral donor sites were followed up. Results: The total radiation dose of modified CTA scan was lower than that of the traditional CTA scan. A total of 48 perforators of double thighs were observed, among which, 31 (64.6%) perforators went outward and downward, 9 (18.8%) perforators went inward and downward, 6 (12.5%) perforators went outward and upward, and 2 (4.2%) perforators went inward and upward, and the average length of superficial fascia perforators was 19.94 mm. The preoperative observed type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery were basically consistent with the intraoperative exploration. The types of 15 septocutaneous (including musculoseptocutaneous) perforators and 10 musculocutaneous perforators observed before the operation was consistent with intraoperative exploration. The distance between the mark of the surface perforator point and the actual exit point of the perforator during operation was (0.38±0.11) mm. All flaps survived without vascular crisis. The donor site wounds of 5 cases of skin grafting and 17 cases of direct suturing wounds healed well. The postoperative follow-up was 2 months to 1 year, with an average of 8.2 months, the flaps were soft and slightly bloated; the function of diet and mouth closing was accessible in patients with oral and maxillofacial tumors, the speech function was mildly impaired in patients with tongue cancer, but they could complete basic oral communication; the wrist and elbow joints and forearm rotation function were not significantly limited in patients with upper limb soft tissue injuries; there was no obvious tightness in the donor sites, and the function of the hip and knee joints was not limited. Conclusions: The whole perforator and even the subcutaneous perforator of the donor site of ALTF can be evaluated by modified CTA, and the flap can be used in oral or maxillofacial reconstruction and repair of skin and soft tissue defects of upper limbs to achieve good results. By clarifying the type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery before the operation, the eccentric design of the ALTF based on the superficial fascia perforator was realized. This study has strong guiding value.
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Angiografía por Tomografía Computarizada , Muslo , Femenino , Masculino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Estudios Prospectivos , Tejido Subcutáneo , Tomografía Computarizada por Rayos XRESUMEN
We analyzed and summarized the imaging characteristics and clinical data of seven pediatric supratentorial embryonal tumors with multilayered rosettes (ETMR). There were four boys and three girls aged from two to six years old. Pediatric supratentorial ETMR often presented large cystic and solid mass, calcification, significant mass effect and mild peritumoral edema. The solid part often showed heterogeneous mild enhancement. In combination with the location of tumor and age of onset, the typical imaging manifestations of supratentorial ETMR in children are valuable for accurate diagnosis.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Neoplasias de Células Germinales y Embrionarias , Tumores Neuroectodérmicos Primitivos , Masculino , Femenino , Humanos , Niño , Preescolar , Neoplasias Encefálicas/patología , Tumores Neuroectodérmicos Primitivos/patologíaRESUMEN
The incidence of anastomotic leakage, a common and serious postoperative complication of low rectal cancer, remains high. Clarifying the risk factors for anastomotic leakage in patients with low rectal cancer after surgery can help guide clinical treatment and help patients improve their prognosis. The current literature suggests that the risk factors affecting the occurrence of anastomotic leakage after low rectal cancer include three aspects: (1) individual factors: male gender, high body mass index, malnutrition, smoking, alcoholism, and metabolic diseases; (2) tumor factors: the lower margin of tumor <5 cm from the anal verge, tumor diameter >2.5 cm, late tumor stage, high level of tumor markers and preoperative intestinal obstruction; (3) surgical factors: long operative time (>180 min), intraoperative bleeding (≥70 ml), more than 2 cartridges of stapling for anastomosis, contamination of the operative field, epidural analgesia and intraoperative hypothermia. Notably, the surgical approach (laparoscopic, open and hand-assisted laparoscopic surgery) was not a factor influencing the occurrence of postoperative anastomotic leakage in low rectal cancer. The findings on the effects of receiving neoadjuvant therapy, gut microbiota,intestinal bowel preparation, insufficient time for preoperative antibiotic prophylaxis, left colonic artery dissection, intraoperative blood transfusion, pelvic drainage, transanal drainage and combined organ resection, and postoperative diarrhea on postoperative anastomotic leakage in low rectal cancer are controversial. However, clinical workers can still take measures to reduce the risk of anastomotic leakage according to the above risk factors by making a good assessment before surgery, actively avoiding them during and after surgery, and taking measures for each step, so as to bring maximum benefits to patients.
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Laparoscopía , Neoplasias del Recto , Humanos , Masculino , Fuga Anastomótica/prevención & control , Recto/cirugía , Neoplasias del Recto/cirugía , Neoplasias del Recto/complicaciones , Anastomosis Quirúrgica/efectos adversos , Laparoscopía/efectos adversosRESUMEN
OBJECTIVE: High glucose can promote the apoptosis of glomerular mesangial cells and cause diabetic nephropathy (DN). However, the mechanism remains unclear. In the present study, we investigated the effects of high glucose on the survival of human renal mesangial cells (HRMCs). MATERIALS AND METHODS: Cells were treated with high glucose (30 mM) or normal glucose (5 mM) for 48 hours. Cell proliferation was determined by trypan blue assay. The relative expression of metalloproteinase-3 (TIMP3) and inflammatory factors detected by real-time polymerase chain reaction (PCR). Protein expression of Smad2/3, p-Smad2/3 and Smad7 in HRMCs were analyzed by Western blot. RESULTS: Compared with normal glucose, we found that high glucose significantly inhibited cell survival, accompanied by the decrease of tissue metalloproteinase-3 (TIMP3) mRNA expression. Western blot results showed that the expression of p-Smad2/3 was significantly up-regulated, the expression of Smad7 was significantly downregulated, and inflammatory factors IL-6/IL-8 mRNA expression were increased in the HRMCs cultured with the high glucose. We also found that, compared with the normal glucose, the level of MDA was significantly increased (p<0.01), and the level of SOD was significantly lower (p<0.05) in the HRMCs cultured with the high glucose. CONCLUSIONS: These findings suggested that high glucose inhibited the survival of HRMCs and may be associated with the downregulation of TIMP3 expression, Smad signaling pathway, inflammation and oxidative stress.
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Nefropatías Diabéticas , Células Mesangiales , Nefropatías Diabéticas/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Humanos , ARN Mensajero/metabolismo , Transducción de SeñalRESUMEN
Objective: To investigate the current situation of occupational exposure to noise among noise workers in an automobile manufacturing enterprise in Tianjin, understand the impact of noise on workersï¼ nervous system and hearing, and assess the risk of hearing loss among noise workers. Methods: In May 2021, 3516 workers in an automobile manufacturing enterprise were investigated by using a self-made questionnaireï¼Noise Workers Questionnaireï¼ and cluster sampling method. The occupational noise hygiene survey and occupational hazards detection were carried out in their workplaces. They were divided into noise exposure group and non-noise exposure group according to whether they were exposed to noise or not. The general characteristics, hearing and nervous system symptoms of the two groups of workers were compared, and the risk of hearing loss was assessed. Results: There were 758 workers in the noise exposure group, aged (26±5) years old, with a working age of 3.0 (2.0, 6.0) years exposed to noise. 2758 workers in the non-noise exposure group, aged (25±6) years old, with a working age of 2.0 (1.0, 4.0) years. There were statistically significant differences in the distribution of workersï¼education level, working age and memory loss between the two groups (χ(2)=37.98, 38.70, 5.20, P<0.05). The workers in the noise exposure group showed a decreasing trend of insomnia, dreaminess, sweating and fatigue with the increase of working age (χ(2trend)=6.16, 7.99, P<0.05). The risk classification of binaural high-frequency hearing loss for workers in all noise positions until the age of 50 and 60 was negligible, the risk of occupational noise deafness was low for workers in stamping and welding noise positions until the age of 60. Conclusion: The occupational noise exposed to automobile manufacturing workers may cause certain harm to their nervous and auditory systems. Noise protection measures should be taken to reduce the risk of hearing loss and occupational noise deafness.
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Sordera , Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Adulto , Automóviles , Pérdida Auditiva Provocada por Ruido/diagnóstico , Pérdida Auditiva Provocada por Ruido/epidemiología , Humanos , Ruido en el Ambiente de Trabajo/prevención & control , Enfermedades Profesionales/diagnóstico , Medición de Riesgo , Adulto JovenRESUMEN
Objective: To learn about the noise exposure and health status of workers and analyze factors that may affect the health outcomes of workers in an auto manufacturing enterprise in Tianjin City. Methods: In September 2020, occupational hygiene survey, noise exposure level detection and occupational health examination data collection were carried out in an auto parts manufacturing enterprise. Chi square test and unconditional logistic regression analysis were used to analyze the health effects of noise exposure and hearing loss of 361 noise exposure workers. Results: The rates of over-standard noise exposure, hearing loss and hypertension were 69.39% (34/49) , 33.24% (120/361) and 11.36% (41/361) , respectively. There were upward trends on age and noise-working years for hearing loss and hypertension rates (χ(2)=-5.95, -6.16, -2.81, -2.74, P<0.05) . Unconditional logistic regression analysis showed that age>35 years old, noise exposure length of service >10 years and noise L(EX, 8 h)>85 dB (A) were risk factors for hearing loss (OR=3.57, 95%CI: 1.09, 11.75; OR=4.05, 95%CI: 1.97, 8.25; OR=1.75, 95%CI: 1.00, 3.05; P=0.036, 0.001, 0.047) . Conclusion: This company has a high rate of job noise exceeding the standard, and noise-exposed workers have more serious hearing loss. Age, noise exposure and high noise exposure are risk factors for hearing loss.
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Sordera , Pérdida Auditiva Provocada por Ruido , Hipertensión , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Exposición Profesional , Adulto , Automóviles , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Humanos , Hipertensión/complicaciones , Ruido en el Ambiente de Trabajo/efectos adversos , Enfermedades Profesionales/complicaciones , Exposición Profesional/efectos adversos , Exposición Profesional/análisisRESUMEN
Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
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Citarabina , Leucemia Mieloide Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Femenino , Homoharringtonina/uso terapéutico , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Proteínas Nucleares , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . â The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. â¡The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . â¢The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Neutropenia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Citarabina/uso terapéutico , Humanos , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Estudios Prospectivos , Recurrencia , Estudios RetrospectivosRESUMEN
Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/patología , Pronóstico , Receptor de Muerte Celular Programada 1 , Estudios RetrospectivosRESUMEN
BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.
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Trastornos del Olfato , Olfato , Humanos , Trastornos del Olfato/etiología , Resultado del Tratamiento , Endoscopía/métodos , Colgajos QuirúrgicosRESUMEN
OBJECTIVE: Angiogenesis impairment is a common feature of diabetes mellitus (DM), whereas CD117+ bone marrow cells (BMCs) injury might be responsible for such complication. In this study, we studied the effect of hyperglycemia on the DNA damage and senility of CD117+ bone marrow cells. MATERIALS AND METHODS: We isolated CD117+ BMCs from the Streptozotocin (STZ) induced diabetes and healthy control mice. Oxidative stress was detected by flow cytometric analysis. γ-H2AX, which is the DNA damage mark, was detected by using Western blotting and immunofluorescence histochemistry. We also detected the expression of γ-H2AX and p16 by using Western blotting. RESULTS: Compared with the control mice, the level of reactive oxygen species (ROS) was increased significantly in the CD117+ BMCs collected from the diabetic mice (p<0.05), and the percentage of γ-H2AX positive cells was higher significantly (p<0.01). The expression of γ-H2AX and p16 was increased significantly in the CD117+ BMCs from the diabetic mice. CONCLUSIONS: Our experiments demonstrated the oxidative stress in CD117+ BMCs under DM conditions, while accelerating the DNA damage and senility in CD117+ BMCs as well.
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Diabetes Mellitus Experimental , Hiperglucemia , Animales , Células de la Médula Ósea/metabolismo , Daño del ADN , Diabetes Mellitus Experimental/metabolismo , Hiperglucemia/metabolismo , Ratones , Estrés Oxidativo , Células Madre/metabolismoRESUMEN
A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe.
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Objective: To investigate the concerns of adult patients with chronic myeloid leukemia (CML) in the chronic phase receiving tyrosine kinase inhibitor (TKI) therapy in China. Methods: A cross-sectional questionnaire including 23 issues of concern was filled by patients with CML nationwide from August to September 2021. The results were compared with those from 2015 to 2016. Results: Data from 952 questionnaires were analyzed. The five most concerned issues were "TKI-related adverse effects and management" (66%) , "stopping TKI therapy" (46%) , "CML risk assessment" (46%) , "TKI dose reduction" (42%) , and "restrictions in daily life activities" (41%) . Compared with the results from 2015 to 2016, patients paid more attention to "TKI-related adverse effects and management" , "monitoring" , and "interpretation of laboratory reports" (all P<0.01) . Concerns of "TKI reimbursement policies" , "price reduction of TKIs" , and issues related to generic TKIs decreased significantly (all P<0.01) . Multivariate analysis showed that female patients (OR=1.8, 95% CI 1.4-2.5, P<0.001) , elderly patients (OR=1.0, 95% CI 1.0-1.0, P<0.001) , or patients with bachelor's degree or higher (OR=1.8, 95% CI 1.3-2.4, P<0.001) were more concerned with "TKI dose reduction" than others. Patients with a bachelor's degree or higher (OR=1.6, 95% CI 1.2-2.2, P=0.002) paid more attention to "CML risk assessment" , whereas those currently receiving a second- or third-generation TKI therapy (OR=1.9, 95% CI 1.3-2.6, P<0.001) were more concerned about "TKI resistance" . Conclusion: Patients with CML paid the most attention to "TKI-related adverse effects and management" , "stopping TKI therapy" , "CML risk assessment" , "TKI dose reduction" , and "restrictions in daily life activities" . Patients' sociodemographic covariates and treatment status were associated with their concerns.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas , Adulto , Humanos , Femenino , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Transversales , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Encuestas y Cuestionarios , China/epidemiologíaRESUMEN
Objective: To explore the current status of alcoholic hepatitis diagnosis by clinicians' in China. Methods: Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases. Results: Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively. Conclusion: Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.
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Enfermedad Hepática en Estado Terminal , Hepatitis Alcohólica , Adulto , China/epidemiología , Femenino , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/epidemiología , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The purpose of this study was to explore the effect of liraglutide on pancreatic islet ß cell apoptosis in rats with type 2 diabetes mellitus (T2DM) and the potential mechanisms. MATERIALS AND METHODS: SD rats were randomly divided into control group, model group, and liraglutide groups (200 and 100 µg/(kg·d)). Rats were fed with high sugar and high-fat diet for 8 weeks, and then streptozotocin (STZ) 40 mg/kg was intraperitoneally injected to establish T2DM model. After successful modeling, rats in the intervention group were given liraglutide through subcutaneous injection for 6 weeks. The indexes of glucose metabolism and lipid metabolism were measured. Apoptosis of islet ß cells was detected by TUNEL. Western blot and RT-PCR were used to detect the protein and mRNA expression levels of IKK ε, NF-κ B, Bcl-2, Bax, IL-6, and Gal-3 in pancreatic tissue. RESULTS: Compared with the control group, the serum FPG, INS, HOMA-IR, TC, TG, LDL-C, IL-6, islet apoptosis rate, glucagon, the positive expression rate of Gal-3, and body weight in the T2DM group were all significantly increased (p<0.05). However, the levels of insulin, SOD, HDL, and HOMA-ß were notably decreased in the T2DM group in comparison with the control group (p<0.05). Moreover, the mRNA and protein expression levels of IKKε, NF-κB, Bax, IL-6, and Bax/Bcl-2 were markedly increased in pancreatic tissue (p<0.05). After liraglutide treatment, these changes were reversed in a dose-dependent manner. CONCLUSIONS: Liraglutide improves pancreatic islet ß cell apoptosis in rats with type 2 diabetes mellitus by inhibiting the IKKε/NF-κB pathway.