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Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.
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Anticuerpos Monoclonales Humanizados , Arritmias Cardíacas , Infarto del Miocardio , Ratas Sprague-Dawley , Receptores de Interleucina-6 , Animales , Masculino , Infarto del Miocardio/complicaciones , Ratas , Arritmias Cardíacas/etiología , Receptores de Interleucina-6/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/farmacología , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant (P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.
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Neoplasias Esofágicas , Cinesinas , Humanos , Pronóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Mapas de Interacción de Proteínas , Proteínas de Unión al ARNRESUMEN
Objective: To establish a method for the determination of two perfluorinated compounds in urine by liquid chromatography-tandem mass spectrometry. Methods: In November 2022, urine samples were extracted by acidic methanol, purified by WAX solid phase extraction column, and eluted with methanol water, then Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) was used with 1.0 mmol/L ammonium acetate solution and methanol as mobile phase. The gradient elution was carried out, the detection was carried out by electrospray negative ion multiple response monitoring (MRM) mode, and the quantitative method was internal standard method. Results: Perfluorooctanoic acid and perfluorooctane sulfonic acid had a good linear relationship in the concentration range of 0.5-50.0 µg/L, and the correlation coefficient was >0.999. The limit of detection was 0.017 µg/L, and the limit of quantitation was 0.005 µg/L. The average recoveries were 96.3% and 101.8%, respectively. Days of precision were 3.5%-6.2% and 3.1%-7.4%, respectively, daytime precision were 4.3%-6.8% and 4.7%-8.1%, respectively. Conclusion: The established method of liquid chromatography-tandem mass spectrometry is high sensitivity and accuracy, and is suitable for the determination of perfluorooctanoic acid and perfluorooctane sulfonic acid in human urine.
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Ácidos Alcanesulfónicos , Caprilatos , Fluorocarburos , Metanol , Espectrometría de Masas en Tándem , Humanos , Cromatografía Líquida de Alta Presión , Cromatografía Liquida/métodos , Extracción en Fase SólidaRESUMEN
Objective: To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS. Methods: In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI(-)) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results: The linear ranges of TCC and TCS were 0.5-100.0 µg/L and 1.0-100.0 µg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 µg/L, and 0.5 and 1.0 µg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 µg/L. Conclusion: QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.
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Carbanilidas , Triclosán , Triclosán/análisis , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Acetonitrilos , Extracción en Fase SólidaRESUMEN
Objective: To establish a method for the rapid determination of the three metabolites of xylene, 2-methylmarmaluronic acid, 3-methylmarmaluronic acid and 4-methylmarmaluronic acid, in urine of occupationally exposed workers by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) . Methods: In July 2022, urine samples were diluted and extracted with pH=6.86 phosphate cache solution, cleaned up by a MAX solid-phase extraction (SPE) column and separated by an Accucore Ph/Hexyl column (100 mm×2.1 mm, 2.6 µm) with a gradient of 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and methanol as mobile phases. The analysis was carried out in electrospray ionization mode and full mass-data dependent secondary mass spectrometry mode, and quantified by external standard method. The characteristics of each index of this method were analyzed. Results: A good linearity was obtained in the concentration range of 1.0-200.0 µg/L for 2-methylmuramic acid, 3-methylmuramic acid and 4-methylmuramic acid with the correlation coefficients of 0.9979-0.9993. The limits of detection of the method were 0.18-0.24 µg/L. While the spiked recoveries at the three concentrations (1.0 µg/L, 100.0 µg/L, and 180.0 µg/L) were in the range of 83.0%-93.7%, with the relative standard deviations of 2.2%-7.9%. Conclusion: The UPLC-HRMS method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the three metabolites of xylene in the urine of occupationally exposed workers.
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Espectrometría de Masas en Tándem , Xilenos , Humanos , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Extracción en Fase SólidaRESUMEN
Aim: Metformin is a first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM), due to its inhibition of hepatic gluconeogenesis. Wingless family member 5a (Wnt5a) was significantly decreased in newly diagnosed T2DM patients and regulates secretion of ß cells through the Wnt/calcium signalling cascades. This study aims to investigate how metformin works on glucose-lowering effects in diabetes and whether the mechanism underlying it is associated with Wnt5a. Methods: A total of 144 participants were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters were evaluated in normal weight, overweight and obese new-onset T2DM subjects grouped. Results: Wnt5a was increased in overweight T2DM patients and obese T2DM patients compared with the levels in normal Body Mass Index (BMI) T2DM. The level of Wnt5a gradually increased after 3 and 6 months of metformin treatment. Among the three groups, the most significant improvement in blood glucose was observed in the obese type 2 diabetic patients, and the improvement showed a significant correlation with Wnt5a protein after patients received metformin treatment. Pearson correlation showed that there was a significant relationship between â³2hOGTT and Wnt5a. After further adjusting for sex and age, a significant association existed only between Wnt5a and 2-h oral glucose tolerance test(2hOGTT), and this association was negative. Conclusion: Our results indicate that Wnt5a may play a role in the mechanism by which metformin improves blood glucose in patients with type 2 diabetes.
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Objective: To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV. Methods: Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR. Results: A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant (χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions: There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.
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Coinfección , Gripe Humana , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Adulto , Humanos , Lactante , China/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/diagnóstico , Gripe Humana/epidemiología , Virus de la Parainfluenza 1 HumanaRESUMEN
OBJECTIVE: To explore the mechanism through which quercetin improves pulmonary arterial hypertension (PAH). METHODS: Rat models of hypoxic pulmonary hypertension were established by exposure to hypoxia for 8-10 h each day (6 days a week for 4 weeks), and before each hypoxic exposure, the rats were given intragastric administration of 100 mg/kg quercetin or saline. After the treatments, the right ventricular systolic pressure (RVSP) and pulmonary artery systolic pressure of the rats were recorded. The right ventricular hypertrophy index (RVHI) was measured to evaluate right ventricular hypertrophy. HE staining was used to observe the remodeling of the pulmonary arterioles. The right cardiac function of the rats was evaluated by ultrasound. The protein levels of HMGB1, RAGE, NF-κB, Bax, Bcl-2 and cleaved caspase-3 in the lung tissue of the rats were detected using Western blotting. RESULTS: Compared with the rats maintained in normoxia, the rats with chronic hypoxic exposure showed significantly increased RVHI and RVSP (P<0.01), which were obviously lowered by quercetin treatment (P<0.01). HE staining showed significant pulmonary artery wall thickening with reduced lumen diameter in hypoxia group, and quercetin treatment effectively improved pulmonary vascular remodeling. Ultrasound examination revealed a significantly increased RVFW and a lowered PAT/PET ratio in hypoxia group (P<0.01), and such changes were ameliorated by quercetin treatment (P<0.01). Chronic hypoxia significantly increased the protein expressions of HMGB1 (P<0.01), RAGE, NF-κB and Bcl-2 (P<0.01) and lowered the protein expressions of Bax and cleaved caspase-3 (P<0.01); Quercetin treatment obviously lowered the protein expressions of HMGB1, NF-κB (P<0.05), RAGE (P<0.01) and (P<0.05) and increased the expressions of Bax and cleaved caspase-3 in the rat models (P<0.01). CONCLUSION: Quercetin improves pulmonary hypertension in rats possibly by promoting apoptosis through the HMGB1/RAGE/NF-κB pathway.
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Proteína HMGB1 , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Ratas , Animales , FN-kappa B/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Quercetina/farmacología , Quercetina/uso terapéutico , Caspasa 3 , Ratas Sprague-Dawley , Hipertrofia Ventricular Derecha , Proteína X Asociada a bcl-2 , Arteria Pulmonar , HipoxiaRESUMEN
OBJECTIVE: To evaluate the therapeutic efficacy of lifetide biofeedback intervention in patients with type 2 diabetes mellitus (T2DM). METHODS: We analyzed the changes in average blood glucose, estimated glycosylated hemoglobin (HbA1c), fasting blood glucose and HbA1c levels in 5 patients with T2DM undergoing lifetide biofeedback intervention without the use of hypoglycemic drugs. A transient blood glucose monitoring system was used for drug withdrawal management during the intervention. RESULTS: Compared with those before the intervention, the average blood glucose and fasting blood glucose and HbA1c levels showed no significant changes after the intervention without using hypoglycemic drugs (P>0.05), but the estimated HbA1c was significantly decreased after the intervention (P<0.05). Two patients achieved complete remission, two showed partial remission, and one had substantially improved blood glucose levels. One patient showed a marked increase in extremity temperature after the intervention (P<0.05). Another patient had a significantly increased heart rate variability index (P<0.05) without obvious changes in heart rate after the intervention (P>0.05). CONCLUSION: By reestablishing the balance in autonomic nervous system regulation and enhancing peripheral microcirculation, lifetide biofeedback intervention helps to maintain stable blood glucose levels, achieve disease remission, and reduce the occurrence of complications in T2DM patients after discontinuation of hypoglycemic drugs without changing their lifestyles.
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Diabetes Mellitus Tipo 2 , Humanos , Glucemia , Hemoglobina Glucada , Automonitorización de la Glucosa Sanguínea , Hipoglucemiantes/uso terapéuticoRESUMEN
Objective: To analyze the epidemiological characteristics and related factors of hepatitis C in Beijing City from 2004 to 2021. Methods: Descriptive epidemiological method and Joinpoint regression were used to analyze the trend and other epidemiological characteristics of hepatitis C in Beijing City from 2004 to 2021 in National Notifiable Disease Reporting System. According to a 1â¶1 matched case-control study design, logistic regression was used to investigate the risk factors of hepatitis C infection in 2021. Results: From 2004 to 2021, the reported incidence of hepatitis C in Beijing City ranged from 2.37/100 000 to 10.46/100 000. The reported cases were mainly aged 30-60 years, and most of them were chronic. The reported incidence of hepatitis C showed an initial increase from 2004 to 2006 (APC=45.37%, 95%CI:-1.56%-114.69%), and declined after 2006 (APC=-9.21%, 95%CI:-10.70%-7.70%). Logistic analysis showed that history of surgery (OR=1.84, 95%CI: 1.08-3.14) and previous blood transfusion (OR=34.22, 95%CI: 8.05-145.41) were risk factors for hepatitis C infection. Conclusion: The reported incidence of hepatitis C in Beijing City increases first and decreases later. It currently remains at a low level. The risk factors of infection are surgery and blood transfusion history. Safe blood supply and preventing iatrogenic transmission should be focused on the prevention of hepatitis C transmission.
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Hepatitis C , Humanos , Beijing/epidemiología , Estudios de Casos y Controles , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Factores de Riesgo , IncidenciaRESUMEN
Objective: Previous studies have found that wnt5a promotes ß-cell insulin secretion and reduced concentrations in patients with type 2 diabetes. GLP-1RA (Glucagon-like peptide-1 receptor agonists) can regulate insulin secretion. However, the evidence that GLP-1RA affect insulin secretion through the Wnt5a is inconclusive. Therefore, this study aimed to evaluate the effect of GLP-1 RA on wnt5a levels in patients with type 2 diabetes. Methods: A total of 56 onset diabetics were selected our study, 29 of them were treated by GLP-1RAs (1.2mg subcutaneous injection once a day, liraglutide, Novo Nordisk), the rest (27 case) treated by Metformin (0.5 g twice a day, Glucophage, Merck). Individuals who were using medications to manage platelet (Aspirin) and cholesterol (Statins) were enrolled and continued treatment throughout the study. Results: Our study found that the waist circumference and insulin secretion index in the GLP-1RA intervention group were significantly increased, and the insulin resistance index was lower than that of the control group. More interestingly, the serum Wnt5a protein level increased dramatically after the GLP-1RA intervention, and the level of Secreted frizzled-related protein 5 (Sfrp5) decreased compared with the control group. Multivariate linear regression analysis showed that the change of HOMA-ß (Homeostasis model assessment- ß) was significantly correlated with the changes of Wnt5a and Sfrp5, and the change of Wnt5a protein was positively correlated with HOMA-ß. Conclusion: Our results confirmed that GLP-1RA may improve HOMA-ß in patients with type 2 diabetes by affecting the level of Wnt5a protein.
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Objective: To explore the effects of hyperandrogenism (HA) on pregnancy outcomes in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: A retrospective study was conducted on infertile women with PCOS undergoing IVF/ICSI-ET from January 2017 to June 2021 in our center. Patients were divided into HA group and NON-HA group according to the levels of testosterone. Propensity score matching (PSM) was used to balance the influence of female age and IVF/ICSI-ET for patients with gonadotropin-releasing hormone (GnRH)antagonist protocol and GnRH agonist protocol, separately. After the PSM procedure, 191 cases in HA group and 382 cases in NON-HA group, were included. Hormone levels and pregnancy outcomes were compared in the two groups. Results: The female age was comparable in two groups [HA: (29.6±3.7) vs NON-HA: (29.5±3.6), P=0.665]. The basal luteinizing hormone [(10.82±6.73) vs (7.76±5.30) IU/L], testosterone [(3.27±0.97) vs (1.60±0.59) nmol/L], free androgen index (7.13 vs 2.77), anti-mullerian hormone [(11.37±5.74) vs (9.67±4.67) ng/ml], fasting glucose [(5.18±0.49) vs (5.06±0.42) mmol/L], 1h glucose [(9.34±2.42) vs (7.99±2.21) nmol/L], 2 h glucose [(7.66±2.17) vs (6.64±1.84) nmol/L], 2 h insulin [(129.81±145.49) vs (97.51±86.92) mU/L], total cholesterol [(5.35±0.89) vs (4.92±0.92) mmol/L], triglycerides [(1.55±1.28) vs (1.33±0.77) mmol/L], and low density lipoprotein cholesterol levels [(3.38±0.66) vs (3.14±0.71) mmol/L] were significantly higher in HA group, compared with NON-HA group (P<0.05). The initiated gonadotropin dose was higher in HA group than that in NON-HA group [(126.96±33.65) vs (137.60±38.12) U, P=0.001], but moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was similar in two groups (P>0.05). The rates of implantation, clinical pregnancy, miscarriage, and live birth were comparable between the two groups (P>0.05). Also, in the subgroups, the rates of implantation, clinical pregnancy, live birth, and miscarriage were similar in HA group and NON-HA group. Conclusions: The risks of hormonal abnormality and glucose-lipid metabolic disorder were higher in PCOS women with HA, whereas satisfactory pregnancy outcomes could be achieved under proper ovarian stimulation undergoing IVF/ICSI-ET.
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Aborto Espontáneo , Hiperandrogenismo , Infertilidad Femenina , Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Masculino , Inyecciones de Esperma Intracitoplasmáticas , Resultado del Embarazo , Estudios Retrospectivos , Infertilidad Femenina/terapia , Índice de Embarazo , Semen , Fertilización In Vitro/métodos , Transferencia de Embrión , Inducción de la Ovulación/métodos , Hormona Liberadora de Gonadotropina , TestosteronaRESUMEN
OBJECTIVE: To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients. METHODS: We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells. RESULTS: The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 µg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 µg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells. CONCLUSION: As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.
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Neoplasias Gástricas , Aldehído Oxidorreductasas , Antígeno CA-19-9 , Antígeno Carcinoembrionario , Gastrectomía , Humanos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patologíaRESUMEN
Objective: To introduce and compare four analysis methods of multiple parallel mediation model, including pure regression method, method based on inverse probability weighting, extended natural effect model method and weight-based imputation strategies. Methods: For the multiple parallel mediation model, the simulation experiments of three scenarios were carried out to compare the performance of different methods in estimating direct and indirect effects in different situations. Dataset from UK Biobank was then analyzed by using the four methods. Results: The estimation biases of the regression method and the inverse probability weighting method were relatively small, followed by the extended natural effect model method, and the estimation results of the weight-based imputation strategies were quite different from the other three methods. Conclusions: Different multiple parallel mediation analysis methods have different application situations and their own advantages and disadvantages. The regression method is more suitable for continuous mediator, and the inverse probability weighting method is more suitable for binary mediator. The extended natural effect model method has better performances when the residuals of two parallel mediators are positively correlated and the correlation degree is small. The weight-based imputation strategies might not be appropriate for parallel mediation analysis. Therefore, appropriate methods should be selected according to the specific situation in practice.
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Análisis de Mediación , Proyectos de Investigación , Sesgo , Simulación por Computador , Humanos , Modelos Estadísticos , Probabilidad , Análisis de RegresiónRESUMEN
Objective: To investigate a preoperative multi-sequence MRI-based radiomic nomogram for prediction of platinum-based chemotherapy sensitivity in patients with epithelial ovarian cancer (EOC). Methods: The complete data of 114 patients with EOC confirmed by surgery and pathology in Nantong Tumor Hospital of Nantong University from January 2015 to May 2020 were retrospectively analyzed, with an average age of 32-76 (57±8) years. All patients underwent platinum-based chemotherapy after maximal cytoreductive surgery. According to whether relapse occurred within 6 months, those patients were divided into platinum-resistant disease (PR, n=39) group and platinum-sensitive disease group (PS, n=75).All patients underwent MRI examination before treatment, and the 3-dimensional solid component of the tumor area of interest (ROI) on T2-weighted image (T2WI), diffusion weighted imaging (DWI) and T1-weighted image-enhanced image (T1CE) were manually delineated using Itk-snap software.Then AK software was imported for radiomics features extracting. They were randomly divided into training group (n=80) and validation group (n=34) in a ratio of 7â¶3 (stratified sampling method). Firstly, the radiomics features were initially screened by the method of maximum correlation and minimum redundancy (mRMR), and features with the greatest predictive power were retained. Then, the LASSO regression analysis was performed to select the best features and construct the radiomics model. Univariate analysis was used to screen out clinical relevant factors, which combined with radiomic score (Radscore) was applied to develop a radiomics nomogram by multivariable logistic regression. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the predictive ability and clinical application value of radiomics model, clinical related factor model and radiomics nomogram. Results: Compared with the radiomics model (12 optimal radiomics features) and the clinical relevant factors model (residual disease, neutrophil count, carbohydrate antigen 199), the radiomics nomogram model demonstrated the best prediction performance: in the training groups, the AUC (Area Under the ROC Curve), accuracy, sensitivity, and specificity were 0.90 (95%CI:0.82-0.99), 90.0%, 89.0%, and 92.0%, respectively. In the validation groups, the AUC, accuracy, sensitivity, and specificity were 0.89 (95%CI:0.78-1.00), 85.0%, 87.0%, and 80.0%, respectively. DCA shows that the use of nomograms with a threshold in the range of 0.01 to 0.90 has a greater clinical application value in predicting the sensitivity of platinum chemotherapy in patients with EOC. Conclusion: The multi-sequence MRI-based radiomics nomogram has a high diagnostic value in predicting the sensitivity of platinum-based chemotherapy in patients with EOC.
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Nomogramas , Neoplasias Ováricas , Adulto , Anciano , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Objective: To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy. Methods: The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1(+) AML and 56 patients with CBFß-MYH11(+) AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results: The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFß-MYH11(+) AML than in those with RUNX1-RUNXIT1 (+) AML (P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1(+) AML, did not affect DFS (P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1(+) AML (P<0.001) , and allo-HSCT significantly prolonged DFS in these patients (P=0.010) . Conclusions: KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1(+) AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-kit/genética , Adolescente , Adulto , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Mutación , Pronóstico , Adulto JovenRESUMEN
Objective: To investigate the effect of programmed death receptor (PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer. Methods: Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected. At the same time, all of the above-mentioned hepatitis B virus (HBV) patients were treated with nucleos(t)ide analogues. Patients clinical diagnostic data, laboratory test results, tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety, therapeutic anti-tumor effect, HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy, high viral load treatment condition, and HBV reactivation safety issues. Statistical analysis was performed by non-parametric rank sum test. Results: Therapeutic anti-tumor effect and safety profile were good in patients. The complete remission rate was reached 27.6%. Adverse reactions were mostly mild, and the incidence of serious adverse reactions was low. After 12 weeks of follow-up, HBV DNA and hepatitis B surface antigen (HBsAg) was quantitatively decreased (P < 0.05). HBV DNA and HBsAg were decreased more significantly in patients with progressive disease (PD), stable disease (SD) and partial response (PR) (P < 0.05). Five patients with HBV DNA ≥ 10(4) IU/ml had responded well to the tumor treatment without serious adverse reactions. One patient had a slight increase in HBV DNA and alanine aminotransferase, while there was no HBV reactivation and correlated liver damage. Conclusion: Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile. PD-1 treatment has a certain effect on HBV. Compared with non-responders, patients with tumor response have better antiviral treatment efficacy. The safety of treatment in patients with high viral load is manageable, and there are no safety issues related to HBV reactivation.