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Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.
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Neoplasias de la Mama , Recurrencia Local de Neoplasia , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Recurrencia Local de Neoplasia/genética , Pronóstico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Estudios Retrospectivos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Timely and accurate identification of harmful bacterial species in the environment is paramount for preventing the spread of diseases and ensuring food safety. In this study, laser-induced breakdown spectroscopy technology was utilized, combined with four machine learning methods - KNN, PCA-KNN, RF, and SVM, to conduct classification and identification research on 7 different types of bacteria, adhering to various substrate materials. The experimental results showed that despite the nearly identical elemental composition of these bacteria, differences in the intensity of elemental spectral lines provide crucial information for identification of bacteria. Under conditions of high-purity aluminum substrate, the identification rates of the four modeling methods reached 74.91%, 84.05%, 85.36%, and 96.07%, respectively. In contrast, under graphite substrate conditions, the corresponding identification rates reached 96.87%, 98.11%, 98.93%, and 100%. Graphite is found to be more suitable as a substrate material for bacterial classification, attributed to the fact that more characteristic spectral lines are excited in bacteria under graphite substrate conditions. Additionally, the emission spectral lines of graphite itself are relatively scarce, resulting in less interference with other elemental spectral lines of bacteria. Meanwhile, SVM exhibited the highest precision rate and recall rate, reaching up to 1, making it the most effective classification method in this experiment. This study provides a valuable approach for the rapid and accurate identification of bacterial species based on LIBS, as well as substrate selection, enhancing efficient microbial identification capabilities in fields related to social security and military applications.
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Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Silicosis , Tuberculosis Pulmonar , Humanos , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tuberculosis Pulmonar/complicaciones , Micobacterias no Tuberculosas , Silicosis/complicacionesRESUMEN
Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Antígeno Prostático Específico/análisis , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.
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Enteritis , Neoplasias Pélvicas , Traumatismos por Radiación , Humanos , Recto , Resultado del Tratamiento , Neoplasias Pélvicas/radioterapia , Traumatismos por Radiación/terapia , Grupo de Atención al PacienteRESUMEN
Objective: To preliminarily analyze the application experience of veno-arterio-venous extracorporeal membrane oxygenation (VAV-ECMO).The VAV-ECMO is a rescue strategy for patients with extremely critical respiratory failure combined with refractory shock. Methods: From February 2016 to February 2022, the characteristics and outcomes of patients who were started on either veno-venous or veno-arterial ECMO due to respiratory or hemodynamic failure, and then converted to VAV-ECMO in respiratory intensive care unit (ICU) of Beijing Chaoyang Hospital were analyzed. Results: A total of 15 patients underwent VAV-ECMO, aged 53 (40, 65) years, and 11 of whom were male. Within the group, VV-ECMO was initially used in 12 patients due to respiratory failure, but then VAV-ECMO was used due to cardiogenic shock (7/12) and septic shock (4/12), while VAV-ECMO was established in two patients due to lung transplantation. One patient was diagnosed with pneumonia complicated by septic shock, which was initially determined to be VA-ECMO, but then switched to VAV-ECMO because it was difficult to maintain oxygenation. The time from the establishment of VV or VA-ECMO to the switch to VAV-ECMO was 3 (1, 5) days and the VAV-ECMO support time was 5 (2, 8) days. ECMO-related complications were bleeding, mostly in the digestive tract (n=4) and airway hemorrhage (n=4), without intracranial hemorrhage, and poor arterial perfusion of the lower limbs (n=2). Among these 15 patients, the overall ICU mortality was 53.3%. The mortality of patients who received VAV-ECMO due to septic shock and cardiogenic shock was 100% (4/4) and 42.8% (3/7), respectively. Two patients who received VAV-ECMO due to lung transplantation all survived. Conclusion: VAV-ECMO may be a safe and effective treatment for carefully selected patients with critical respiratory failure associated with cardiogenic shock or end-stage lung disease lung transplantation transition, however, patients with septic shock may benefit the least.
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Oxigenación por Membrana Extracorpórea , Trasplante de Pulmón , Insuficiencia Respiratoria , Choque Séptico , Humanos , Masculino , Femenino , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Choque Séptico/complicaciones , Choque Séptico/terapia , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiología , Estudios RetrospectivosRESUMEN
Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.
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Productos Biológicos , Exenteración Pélvica , Neoplasias del Recto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Productos Biológicos/uso terapéutico , Diafragma Pélvico/cirugía , Diafragma Pélvico/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/cirugía , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Osteoarthritis (OA) has the highest disability rate among chronic diseases. The burden on patients and public health care resources is increasingly evident due to increasing obesity rates and aging populations. So, there is still a lack of early diagnosis and treatment for OA. MATERIALS AND METHODS: A total of three OA cartilage tissue datasets (GSE1919, GSE32317, and GSE5235) were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially expressed genes and WGCNA of overlapping genes were performed using the R language package. Functional and immune infiltration analyses of overlapping genes were also carried out while hub genes were screened through LASSO regression analysis method and ROC curve. Finally, experimental validation was carried out through PCR and Western Blot analysis of rat cartilage. RESULTS: A total of 149 differentially expressed genes were screened, and they were mainly enriched in the cytokine-cytokine receptor interaction, rheumatoid arthritis, and interleukin (IL-17) signaling pathways. Four co-expression modules were obtained, of which the blue module was the most substantial morbidity associated with OA. Thirteen overlapping genes were identified based on significant module network topology analysis and differential genes, upon which their validation through LASSO regression analysis method and ROC curve was performed. From these, five signature genes were determined, before three potential core genes were finally identified after confirmation using the validation set. CONCLUSIONS: ATF3, FOSL2, and GADD45B may be hub genes to the osteochondropathy, and they are expected to be new biomarkers and drug targets in OA research.
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Artritis Reumatoide , Osteoartritis , Animales , Ratas , Cartílago , Investigación , Osteoartritis/genética , Curva ROC , Antígenos de DiferenciaciónRESUMEN
Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q1, Q3). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q1, Q3) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ2=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ2=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ2=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.
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Recuperación Mejorada Después de la Cirugía , Neoplasias Gástricas , Femenino , Gastrectomía , Humanos , Tiempo de Internación , Masculino , Dolor , Evaluación del Resultado de la Atención al Paciente , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 µg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.
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Aminobutiratos , Apelina , Insuficiencia Cardíaca , Valsartán , Remodelación Ventricular , Aminobutiratos/farmacología , Animales , Apelina/metabolismo , Compuestos de Bifenilo , Colágeno/metabolismo , Doxorrubicina/farmacología , Fibrosis , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/patología , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Valsartán/farmacología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Objective: To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) . Methods: This prospective, multicenter, open label, single-arm, phase â ¡ study investigated bendamustine's efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed. Results: The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage â ¢/â £ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS (P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS (P=0.009) . Conclusion: Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.
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Clorhidrato de Bendamustina , Linfoma de Células B , Recurrencia Local de Neoplasia , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Clorhidrato de Bendamustina/efectos adversos , Linfoma de Células B/tratamiento farmacológico , Neutropenia/inducido químicamente , Estudios Prospectivos , Trombocitopenia/inducido químicamente , China , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
Objective: To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces. Methods: From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted. Results: A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95%CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95%CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95%CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95%CI:-2.05, -0.48). Conclusion: The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.
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Hipertensión , Sodio en la Dieta , Adolescente , Adulto , Anciano , Presión Sanguínea , China , Humanos , Persona de Mediana Edad , Potasio , Sodio , Cloruro de Sodio Dietético , Adulto JovenRESUMEN
OBJECTIVE: Dynamic monitoring of CTCs/CSCs can assist in the diagnosis and prognosis of tumors. This study explores the diagnostic significance of microfluidic chip technology in the detection of CTCs/CSCs in clinical staging and metastasis of patients with non-small cell lung cancer (NSCLC). That lays a solid foundation for the use of microfluidic chips to monitor CTCs/CSCs for the stage and metastasis of patients with non-small cell lung cancer. PATIENTS AND METHODS: This study collected 80 patients with lung cancer from October 2017 to October 2018. Meanwhile, 30 healthy people and 30 patients with benign lung diseases were selected during the same period as the control group 1 and the control group 2, respectively. CellSearch (Huntington Valley, PA, USA) and microfluidic chip were used to detect CTCs, the sensitivities were recorded. ELISA methods were used to detect the concentrations of tumor markers VEGF-C, CEA, and CA125 in serum, and their association with CTCs and CSCs was analyzed. In addition, after 3 months, we followed up 40 patients with lung cancer, recorded their prognosis, and extracted peripheral blood to detect changes in their CTCs and CSCs. The CellSearch (Huntington Valley, PA, USA) system and the microfluidic chip system were used to detect the CTCs in patients with lung cancer, and the sensitivity and specificity of the patients were analyzed. The changes in CTCs and CSCs in the peripheral blood of the patient were recorded. RESULTS: It can be seen that the positive rate of CTCs and CSCs is not significantly correlated with the patients' age, gender, pathological type (adenocarcinoma, squamous cell carcinoma), etc. They are significantly correlated with clinical stage (I + II and III + IV) and metastasis (metastasis and non-metastasis) (p<0.01). Then, we divided the patients into groups for testing, and analyzed the association between different groups of patients and CTCs and CSCs. Compared with control group 1 and control group 2, the positive rates of CTCs and CSCs in lung cancer metastasis group and non-metastasis group were significantly different (p<0.05). Compared with the control group 1 and control group 2, the positive rates of CTCs and CSCs in stage I + II and III + IV of lung cancer were significantly different (p<0.05). The positive rate was significantly higher in the cancer metastasis group (p<0.05). The concentrations of tumor markers VEGF-C, CEA, CA125 in the serum of patients were consistent with CTCs-negative and CTC-positive lung cancer, with significant differences (p<0.05). CSCs negative and CSCs positive patients have similar results. Subsequently, we analyzed the sensitivity and specificity of CSCs, CTCs, and tumor markers for the diagnosis of NSCLC. The results showed that the sensitivity of CSCs and CTCs to diagnose patients was significantly higher than that of tumor markers. CONCLUSIONS: This study shows that our microfluidic chip device can exhibit relatively good performance and can better detect CTCs and CSCs. Monitoring CTCs and CSCs of patients can provide a basis for judging the stage and metastasis of patients.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Dispositivos Laboratorio en un Chip , Neoplasias Pulmonares/diagnóstico , Células Neoplásicas Circulantes/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: To understand the population distribution, density, seasonal fluctuation and nocturnal activity of malaria vectors in Anhui Province from 2016 to 2018, so as to provide a data support for formulating the control strategy for imported malaria during the malaria post-elimination stage. METHODS: The malaria vectors were monitored in 105 counties (cities or districts) of Anhui Province from 2016 to 2018, and the population density, seasonal fluctuation and nocturnal activity of the mosquitoes were observed using the lamp trapping and human bait trapping methods. The density of Anopheles mosquitoes was compared among different years, regions and mosquito-capturing sites. RESULTS: Anopheles mosquitoes were captured in 103 counties (cities or districts) of Anhui Province during the period from 2016 to 2018, and a total of 32 494 mosquitoes were captured using the lamp trapping method and 36 228 captured using the human bait trapping method. All captured mosquitoes were morphologically identified as Anopheles sinensis, and no An. anthropophagus was found. The density of An. sinensis peaked from June to August, and the peak nocturnal activity was found during the period between 19â¶00 and 23â¶00. Among all mosquito-capturing sites, the highest mosquito density was seen in the livestock and poultry sheds (H = 18.835, P < 0.05). The density of An. sinensis varied significantly in regions in 2016 and 2017 (H = 16.655 and 11.566, P < 0.01), and a low density was found in north of the Huai River. CONCLUSIONS: An. sinensis is widely distributed in Anhui Province, which is the currently predominant malaria vector in the province. During the malaria post-elimination stage, the malaria vector monitoring should be intensified and vector control interventions should be timely adopted in epidemic foci of Anhui Province to prevent the local re-transmission of overseas imported malaria.
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Anopheles , Malaria , Mosquitos Vectores , Distribución Animal , Animales , Anopheles/parasitología , China , Malaria/parasitología , Malaria/transmisión , Mosquitos Vectores/parasitología , Densidad de Población , Estaciones del AñoRESUMEN
Objective: To investigate the effects of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining on clinical prognosis in patients with IgA nephropathy. Methods: From January 1st, 2007 to December 30th, 2016, a total of 519 patients with biopsy-proven IgA nephropathy (IgAN) in West China Hospital were retrospectively reviewed and divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A with IgA/C3 ratio ≥3.046 (median) and glomerular C3 staining ≥2 (n=151), group B with IgA/C3 ratio ≥3.046 and glomerular C3 staining<2 (n=109), group C with IgA/C3 ratio<3.046 and glomerular C3 staining ≥2 (n=119), and group D with IgA/C3 ratio<3.046 and glomerular C3 staining<2 (n=140). Clinical data, pathological characteristics and the primary endpoint [≥ 50% decline in estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD)]were collected. Clinical prognosis and relevant risk factors were analyzed among the four groups. Results: Totally, 519 patients (298 males, 57.4%) with an average age of (33.6±10.9) years were recruited and followed up for (43.4±21.6) months. The rate of complete remission plus partial remission was 74.2% (112/151), 74.3% (81/109), 72.3% (86/119), 81.4% (114/140) in group A, B, C, D, respectively. Meanwhile, The rate of ESRD was highest in group A (14.6% vs 9.2%, 13.4%, 8.6%). Renal outcome (patients reached the endpoint) was worse in group A and C compared with group B and D (15.2%, 16.0 vs 8.3%, 7.9%). Moreover, 80-month renal survival rate was significantly worse in group A (84.8%) than that in group B and D (91.7% and 92.1%), but no statistical significant difference was found between group A and B (P(AB)=0.085; P(AD)=0.028). There was no significant difference of renal survival rate between group A and C (84.8% vs 84.0%, P=0.896). Multivariate Cox model showed that hypertension (HR=2.753, 95%CI: 1.452-5.217, P=0.002), serum creatinine (HR=1.011, 95%CI: 1.008-1.014, P<0.001), and tubular atrophy/interstitial fibrosis (T1/T2) (HR=6.595, 95%CI: 3.107-13.999, P<0.001) were independent predictors of poor renal survival. Conclusion: Serum IgA/C3 ratio and glomerular C3 staining are predictors of renal clinical prognosis in patients with IgA nephropathy.
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Glomerulonefritis por IGA , Adulto , China , Complemento C3/análisis , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Humanos , Inmunoglobulina A , Masculino , Pronóstico , Estudios Retrospectivos , Coloración y Etiquetado , Adulto JovenRESUMEN
Oxic-settling-anaerobic (OSA) process is effective in minimizing sludge production, by inserting an anaerobic side-stream reactor (ASSR) in the recycling bypass. Interchange ratio (IR), the quantity ratio of sludge entering the ASSR to the sludge in the main stream reactors, is one of the most important parameters for OSA process. In the present study, a laboratory-scale anaerobic/anoxic/oxic (A2/O) process combined with an ASSR (A2/O-ASSR) was operated for 366 days in parallel with a conventional A2/O process to investigate the effects of IR on sludge reduction. IR was assigned values of 5%, 8%, 10%, and 15%, and the A2/O-ASSR process achieved 14.0%, 16.0%, 24.1%, and 13.7% of sludge reduction, respectively. At the optimum IR of 10%, high through-put sequencing analysis showed that the microbes responsible for pollutant removal and ubiquitous in wastewater treatment remained predominant in the two systems, and slow-growing microbes related to hydrolysis, nitrogen and phosphorus removal increased in the A2/O-ASSR process, which probably played a key role in sludge reduction. 40.6-58.6% of sludge reduction was caused by sludge decay in the ASSR. The tiny amount of extracellular polymeric substance released in the A2/O-ASSR process was subthreshold to cause remarkable sludge reduction.
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Microbiota , Aguas del Alcantarillado , Anaerobiosis , Reactores Biológicos , Matriz Extracelular de Sustancias Poliméricas , Eliminación de Residuos LíquidosRESUMEN
Beginning in December 2019, coronavirus disease 2019 (COVID-19), due to 2019-nCoV infection, emerged in Wuhan and spread rapidly throughout China and even worldwide. Employing combined therapy of modern medicine and traditional Chinese medicine has been proposed, in which Ma Xing Shi Gan Decoction (MXSGD) was recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. We investigated the underlying mechanism of MXSGD in treating COVID-19 utilizing the approaches of integrating network pharmacology. A total of 97 active ingredients of MXSGD were screened out, and 169 targets were predicted. The protein-protein interaction network exhibited hub targets of MXSGD, such as Heat shock protein 90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP-1, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Vascular endothelial growth factor A, and Tumour necrosis factor. Gene Ontology functional enrichment analysis demonstrated that the biological processes altered within the body after taking MXSGD were closely related to the regulation of such processes as the acute inflammatory response, chemokine production, vascular permeability, response to oxygen radicals, oxidative stress-induced apoptosis, T cell differentiation involved in the immune response, immunoglobulin secretion, and extracellular matrix disassembly. KEGG enrichment analysis indicated that the targets of MXSGD were significantly enriched in inflammation-related pathways, immunomodulation-related pathways, and viral infection-related pathways. The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary edema, regulating the immune response, and decreasing fever.