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Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.
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Neoplasias Encefálicas , Biopsia Guiada por Imagen , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Glioma/patología , Adulto , Anciano , Encéfalo/patología , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/métodosRESUMEN
Objective: To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC). Methods: This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ2 test or Fisher's exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results: According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant(χ2=4.459,P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant(χ2=4.410,P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95%CI: 5.8 to 13.2 months) and 7.3 months (95%CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95%CI: 12.5 to 33.9 months) and 15.9 months (95%CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion: Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Hepatitis B , Neoplasias Hepáticas , Masculino , Femenino , Humanos , Estudios Retrospectivos , Neoplasias Hepáticas/patología , Antígenos de Superficie de la Hepatitis B/uso terapéutico , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Hepatitis B/tratamiento farmacológico , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Carcinoma Hepatocelular/patologíaRESUMEN
Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereâ toâ ¡adverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombosis , Masculino , Humanos , Femenino , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Estudios RetrospectivosRESUMEN
Objective: To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification. Methods: Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC). Results: A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95%CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions: There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Diabetes Mellitus Tipo 1/diagnóstico , Péptido C , Consenso , Pueblos del Este de Asia , Estudios Retrospectivos , AutoanticuerposRESUMEN
Objective: To compare the safety and diagnostic efficiency of CT-guided trans-organ and non-trans-organ large needle biopsy in the diagnosis of pancreatic space-occupying lesions. Methods: The clinical data of 367 patients with pancreatic mass who underwent CT-guided percutaneous biopsy in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed, including 211 males and 156 females, aged 18 to 87 (60.7±11.8) years old. They were divided into a trans-organ route group (n=142) and a non-trans-organ route group (n=225) according to whether traversing the organs during the procedures. The imaging data, pathological results, puncture process and complications of patients of the two groups were recorded. The successful rate for obtaining tissue,one-time successful diagnosis rate, accuracy, sensitivity, specificity, false negative rate and the incidence of complications were compared between the two groups. Results: There was no significant difference in baseline data between the two groups (all P>0.05).There were 28, 57, 24, and 33 biopsies were performed via a pathway traversing liver, stomach, small bowel and colon, respectively. The overall sampling success rates of the two groups were 100%.The one-time successful diagnosis rate did not show statistically difference between the two groups [86.6%(123/142) vs 87.1%(196/225),P=0.892]. There was no statistically difference in accuracy, sensitivity and false negative rates between trans-organ route group and non-trans-organ routegroup [92.3%(131/142) vs 92.0%(207/225), 91.8% (123/134) vs 90.0%(190/211) and 8.2% (11/134) vs 10.0%(21/211), all P>0.05]. The specificity was 100% in both groups. The common complications of the two groups were increased pancreatic amylase and hematoma, and there was no significant difference in the incidence of complications between the trans-organ route group and the non-trans-organ route group [10.6% (15/142) vs 12.4% (28/225), P=0.585]. In the trans-organ route group, 5 patients had increased pancreatic amylase and 10 patients had local hematoma, all of which were improved after conservative treatment. In the non-organ route group, 11 patients had elevated pancreatic amylase, and 17 patients had local hematoma, 1 case received surgical treatment due to bleeding, the rest were improved by conservative treatment. Conclusion: CT-guided percutaneous transabdominal organ large needle biopsy of pancreatic space-occupying lesions has the comparable diagnostic efficiency and safety as non-transabdominal organ approach.
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Biopsia con Aguja Gruesa , Neoplasias Pancreáticas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Amilasas , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto Joven , Adulto , Anciano de 80 o más AñosRESUMEN
The clinical data of ten patients with immune checkpoint inhibitor-related type 1 diabetes mellitus were enrolled in the Second Xiangya Hospital of Central South University from January 2020 to October 2022 including 9 males and 1 female, with an average age of (57±8) years. There were 7 cases of fulminant type 1 diabetes and 3 cases of acute type 1 diabetes. Among the 10 patients, there were 5 cases of lung cancer, 2 cases of esophageal cancer, 1 case of gastric carcinom, 1 case of renal cell carcinoma, and 1 case of nasopharyngeal cancer. The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. Among them, 8 patients had diabetic ketoacidosis (DKA), 1 patient had ketosis, and 1 case had no ketosis at onset; 9 patients were negative for diabetes-related antibodies, and 1 patient was positive. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy.
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Antineoplásicos Inmunológicos , Diabetes Mellitus Tipo 1 , Neoplasias Nasofaríngeas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , InsulinaRESUMEN
Objective: To compare the safety and efficacy of cryoablation(CYA) and radiofrequency ablation(RFA) for stageâ non-small cell lung cancer(NSCLC). Methods: From January 2014 to January 2019, 90 eligible patients [48 males, 42 females, age: 39-85(63.6±10.1)years] in the First Affiliated Hospital of Zhengzhou University met the inclusion criteria were retrospectively analyzed. They were divided into 2 groups according to different treatment methods(group CYA and group RFA). The duration of operation, intraoperative pain, local tumor progression rate and the incidence of complications were compared. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Results: The clinical data and tumor situation of the patients between two groups did not show significant differences. The mean duration of operation for group CYA was longer than that for group RFA [(73.5±17.2)min vs (51.4±18.7)min, P<0.001];the mean intraoperative visual analogue score(VAS)for group CYA was lower than that for group RFA (0.53±0.89 vs 3.44±2.44, P<0.001). The median follow-up period time were 53 months and 52 months for group CYA and RFA. At the end of the study, The local tumor progression rate was 31.6%(12/38) and 25.0%(13/52) for group CYA and group RFA, the difference were not statistically(P=0.491). There was no statistical difference for progress-free survival(PFS)between group CYA and group RFA[51(95%CI:40.3-55.0)months)vs 44(95%CI:37.2-54.1) months, P=0.649]. The median OS was not reached in both groups. The most common complications observed in the two groups were pneumothorax, hemorrhage and pleural effusion. There was no statistical difference in the incidence rates [42.1%(16/38) for group CYA vs 28.8% (15/52)for group RFA, P=0.191]. The incidence rate of pleural effusion for group CYA was higher than that for group RFA [26.3%(10/38)vs 5.8%(3/52), P=0.006]. The incidence rates of pneumothorax and hemorrhage had no statistical difference between the two groups [13.3%(5/38)vs 13.5% (7/52) and 15.8%(6/38) vs 9.6% (5/52), all P>0.05]. Conclusion: Compared with RFA,CYA shows no significant differences in the same efficacy and safety for treating patients with stage â NSCLC, with less intraoperative pain but longer operative duration.
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Carcinoma Hepatocelular , Carcinoma de Pulmón de Células no Pequeñas , Ablación por Catéter , Criocirugía , Neoplasias Hepáticas , Neoplasias Pulmonares , Derrame Pleural , Neumotórax , Ablación por Radiofrecuencia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Dolor , Derrame Pleural/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Diabetes is a group of highly heterogenous diseases with multiple etiopathologies and clinical characteristics. In type 1 diabetes mellitus, there are different endotypes and clinical phenotypes based on genetics, immunology, metabolism and therapeutics. Precision medicine provides novel ideas and strategies for further studies and clinical prevention/control of diabetes. The article summarizes the concepts, progress and future directions of precision medicine for the diagnosis, prevention, treatment, prognosis, and monitoring of diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 1/terapia , Humanos , Fenotipo , Medicina de PrecisiónRESUMEN
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus report on the management of type 1 diabetes in adults in September 2021. The writing group has proposed principles of the diagnosis and management of adult patients with type 1 diabetes, and has made suggestions for glycemic control with individualized glycemic targets to avoid hypoglycemia. They have also emphasized the importance of education and support for the self-management of diabetes in the management of type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglucemia , Adulto , Glucemia , Consenso , Diabetes Mellitus Tipo 1/terapia , Humanos , Hipoglucemiantes , Estados UnidosRESUMEN
Objective: We aimed to investigate the autoimmune status of long-term type 1 diabetes mellitus (T1DM) patients with residual ß-cell function. Methods: The residual ß-cell function of long-term (disease duration≥10 years) autoimmune T1DM patients from the T1DM Integrated Management Clinic of the Second Xiangya Hospital was assessed by serum C-peptide levels. Patients with fasting or 2-hour postprandial C-peptide levels over the lower sensitivity limit of detection (16.7 pmol/L) were grouped as C-peptide-positive, and others were grouped as C-peptide-negative. We screened and enrolled all the C-peptide-positive patients (n=19). C-peptide-negative patients with matched sex, age, duration, BMI (n=19) and healthy controls (n=19) were recruited at the same time. The frequencies of CD4+T cell (Th1/Th2/Th17/Treg) and B cell (MZB/FoB/B10) subsets, the expression of PD-1/PD-L1 on T and B lymphocytes, and the levels of T1DM related cytokines including IFN-γ, TNF-α, IL-1ß, IL-1RA, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-23 and IP-10 were tested. We compared these parameters in patients with different levels of ß-cell function. Results: In healthy controls, C-peptide-negative and C-peptide-positive patients, the frequencies M (Q1, Q3) of Th1 cells were 9.93% (7.45%, 15.20%), 14.90% (11.70%, 18.00%) and 10.20% (6.93%, 15.80%) (P=0.015), and the frequencies M (Q1, Q3) of Treg cells were 3.52% (2.92%, 5.68%),2.88% (1.64%, 3.22%) and 3.12% (2.81%, 4.81%) (P=0.005), and the frequencies M(Q1,Q3) of PD-1+B cells were 4.69% (2.64%, 6.37%), 2.11% (1.45%, 3.63%) and 4.20% (2.53%, 6.01%) (P=0.003), respectively. The levels of IL-6 M(Q1,Q3)were 26.43(18.06, 33.35) ng/L, 42.97 (25.52, 66.30) ng/L, and 22.07 (14.85, 34.45) ng/L (P=0.006), and the levels of IP-10 M(Q1,Q3) were 107.39 (76.19, 126.07) ng/L, 188.82 (131.27, 348.18) ng/L and 128.26 (114.31, 136.50) ng/L (P<0.001) in healthy controls, C-peptide-negative and C-peptide-positive patients, respectively. Compared with C-peptide-positive patients, the frequency of Th1 cells and the levels of IL-6 and IP-10 cytokines were higher, while the frequencies of Treg cells and PD-1+B cells were lower in C-peptide-negative patients (all P<0.05). Conclusions: Long-term T1DM patients with residual ß-cell function had lower frequency of Th1 cells, lower levels of IL-6, IP-10 cytokines, and higher frequencies of Treg and PD-1+B cells, which indicated a pronounced autoimmune tolerance.
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Diabetes Mellitus Tipo 1 , Péptido C , Quimiocina CXCL10/metabolismo , Citocinas/metabolismo , Humanos , Interleucina-6/metabolismo , Receptor de Muerte Celular Programada 1 , Linfocitos T Reguladores/metabolismo , Células TH1/metabolismo , Células Th17/metabolismoRESUMEN
Objective: To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function. Methods: A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q1, Q3)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their ageï¼»Mï¼Q1ï¼Q3ï¼ï¼½was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1ß in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results: The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>Tãc.1564T>Cc.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1ß secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q1, Q3)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010). Conclusions: NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1ß. This result suggests that NLRC4 rare variants may have an impact on gene function.
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Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Caspasa 1/genética , Caspasa 1/metabolismo , Niño , Diabetes Mellitus Tipo 1/genética , Exones , Femenino , Heterocigoto , Humanos , Inflamasomas/genética , Inflamasomas/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1â¶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Neoplasias Gástricas , Quimioradioterapia , Análisis de Datos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Humanos , Estudios RetrospectivosRESUMEN
Currently, the systematized nomenclature of medicine (SNOMED) of liver cancer is confusing, and it is mixed with the SNOMED of cholangiocarcinoma. We hereby presented our own points, hoping to provide a reference for standardizing the nomenclatures and classifications of liver cancer in future clinical studies. The preface of Chinese Guidelines of Primary Liver Cancer Diagnosis and Treatment (2019 Edition) indicated that primary liver cancer mainly includes three different pathological types, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and mixed-type carcinoma of both HCC and ICC. These three types of carcinoma show great differences in terms of pathogenesis, biological behavior, histological morphology, treatment methods, and prognosis, among which, HCC accounts for 85% to 90%. Therefore, this study is a detailed analysis of the above-mentioned related SNOMED and proposes suggestions for corrections.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Conductos Biliares Intrahepáticos , HumanosRESUMEN
Objective: To establish the luciferase immunoprecipitation system assay (LIPS) to test tetraspanin 7 autoantibody (TSPAN7A) and evaluate its value in Chinese type 1 diabetes (T1D) patients. Methods: Renilla luciferase-tagged TSPAN7 plasmids were transfected into 293T cells to obtain Renilla luciferase-tagged TSPAN7 fusion protein. The cell lysate was incubated with sera overnight, followed by addition of protein A-agarose and extensive wash. Finally, the substrate of Renilla luciferase was added and luminescence was detected. Sera from 100 T1D patients [64 males and 36 females,with a mean age of (28±16) years], 119 type 2 diabetes (T2D) patients [78 males and 41 females,with a mean age of (47±12) years] and 98 healthy volunteers [55 males and 43 females,with a mean age of (28±12) years] from the Department of Metabolism and Endocrinology of the Second Xiangya Hospital, Central South University from 2014 to 2017, were tested by LIPS to evaluate the frequency of TSPAN7A. Radioligand binding assay (RLA) was used to test glutamic acid decarboxylase autoantibodies (GADA), protein tyrosine phosphatase-2 autoantibodies (IA-2A) and zinc transporter 8 autoantibodies (ZnT8A). Results: The frequencies of GADA, IA-2A, ZnT8A and TSPAN7A in T1D patients were 72.0%, 40.0%, 29.0% and 25.0%, respectively. After Bonferroni correction, the positivity of TSPAN7A was lower than GADA (P<0.001), but similar with IA-2A (P=0.035) and ZnT8A (P=0.630). The positivity of TSPAN7A in T1D patients was significantly higher than that in T2D (0.84%, P<0.001) and in healthy controls (1.02%, P<0.001). In combination with TSPAN7A, the positivity of islet autoantibodies in T1D patients increased from 82% to 85%. There was no significant difference in clinical characteristics between TSPAN7A-positive T1D and the other three islet autoantibodies-positive patients. Conclusion: This study succeeded in establishing LIPS method to assay TSPAN7A. Moreover, TSPAN7A are valid islet autoantibodies for T1D patients in China.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Autoanticuerpos , Niño , China , Femenino , Glutamato Descarboxilasa , Humanos , Masculino , Persona de Mediana Edad , Tetraspaninas , Adulto JovenRESUMEN
Inflammation is a critical player in the development and progression of colon cancer. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays an important role in infection and tumor immunity through regulating the development of conventional type 1 dendritic cells (cDC1s). However, the function of BATF3 in colitis and colitis-associated colon cancer (CAC) remains unclear. Here, BATF3 wild-type and knockout mice were used to construct an AOM/DSS-induced CAC model. In addition, DSS-induced chronic colitis, bone marrow cross-transfusion (BMT), neutrophil knockout, and other animal models were used for in-depth research. We found that BATF3 deficiency in intestinal epithelial cells rather than in cDC1s inhibited CAC, which was depended on inflammatory stimulation. Mechanistically, BATF3 directly promoted transcription of CXCL5 by forming a heterodimer with JunD, and accelerated the recruitment of neutrophils through the CXCL5-CXCR2 axis, ultimately increasing the occurrence and development of CAC. Tissue microarray and TCGA data also indicated that high expression of BATF3 was positively correlated with poor prognosis of colorectal cancer and other inflammation-related tumors. In summary, our results demonstrate that intestinal epithelial-derived BATF3 relies on inflammatory stimulation to promote CAC, and BATF3 is expected to be a novel diagnostic indicator for colitis and CAC.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Quimiocina CXCL5/metabolismo , Neoplasias Asociadas a Colitis/etiología , Neoplasias Asociadas a Colitis/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Infiltración Neutrófila/inmunología , Proteínas Represoras/metabolismo , Animales , Quimiocina CXCL5/genética , Colitis , Neoplasias Asociadas a Colitis/patología , Neoplasias del Colon/etiología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Mucosa Intestinal/patología , Ratones , Ratones Noqueados , Neutrófilos/inmunología , Neutrófilos/metabolismoRESUMEN
Objective: To compare the efficacy and safety of Changsulin® with Lantus® in treating patients with type 2 diabetes mellitus (T2DM). Methods: This was a phase â ¢, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3â¶1 to Changsulin® or Lantus® treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results: After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin® and in Lantus®, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin® and Lantus® in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin® and Lantus®, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin® and Lantus®, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions: Changsulin® shows similar efficacy and safety profiles compared with Lantus® and Changsulin® treatment was well tolerated in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes/uso terapéutico , Insulina Glargina/uso terapéutico , Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia , Resultado del TratamientoRESUMEN
Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with â £ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage â £ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage â £A patients, and 58.8%, 29.0% and 23.5% in stage â £B patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with â £ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage â £ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/radioterapia , China/epidemiología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIMS: To examine the association between 24 literature-based single nucleotide polymorphisms and diabetic kidney disease in Chinese people with type 2 diabetes. METHODS AND RESULTS: Twenty-four candidate diabetic kidney disease-susceptible single nucleotide polymorphisms were genotyped in 208 participants with type 2 diabetes and diabetic kidney disease and 200 participants with type 2 diabetes without diabetic kidney disease (case and control groups, respectively), together with 206 healthy participants using MassARRAY. Rs11643718 in the SLC12A3 gene was associated with diabetic kidney disease in the recessive model after adjusting for confounding factors, such as age and gender (adjusted odds ratio 2.056, 95% CI 1.120-3.776; P = 0.020). Meta-analyses further confirmed the association (P = 0.002). In addition, participants with the GG genotype had worse renal function and more albuminuria than those with the AA+AG genotype (P < 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease and AA+AG or GG genotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance of SLC12A3 was reduced in patients with the GG genotype, while elevated expression of SLC12A3 was associated with better renal function. In addition, rs10951509 and rs1345365 in ELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjusted P = 0.010 and 0.015, respectively). CONCLUSIONS: The G allele and GG genotype of SLC12A3 rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes.
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Proteínas Adaptadoras Transductoras de Señales/genética , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Nefropatías Diabéticas/etiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Miembro 3 de la Familia de Transportadores de Soluto 12/genéticaRESUMEN
Objective: To examine the effect of pancreaticojejunostomy with pancreatic duct binding external drainage in laparoscopic pancreatoduodenectomy. Methods: The data of 21 patients who underwent laparoscopic pancreaticoduodenectomy in the same treatment group from January 2017 to October 2019 in Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were analyzed retrospectively.All patients underwent pancreaticojejunostomy with external drainage of pancreatic ducts.There were 12 males and 9 females, aged (63.1±8.1)years old (range: 46 to 77 years old), body mass index (24.8±3.2)kg/m(2)(range: 18.8 to 29.1 kg/m(2)).There were 3 cases of hypertension, 5 cases of diabetes, 3 cases of hypertension and diabetes, 3 cases of liver cirrhosis. Results: Laparoscopic pancreatoduodenectomy was successfully performed in all 21 patients.The operation time was (359.3±71.0)minutes, the pancreaticojejunostomy time was (23.8±7.4)minutes, the diameter of pancreatic duct was(3.3±0.6)mm, the intraoperative blood loss was (247.6±90.1)ml, the postoperative hospital stay was(13.7±4.9)days, the leakage of B-level fistula occurred in 1 case(4.8%), and there was no C-level pancreatic fistula.There were 3 cases of bile leakage, 1 case of incision infection, 2 cases of gastroparesis, 1 case of hydrops abdominis, no death and secondary operation. Conclusion: It is a simple and easy method of pancreatoenterostomy with pancreatic duct binding external drainage, which can reduce the incidence of pancreatic fistula and related complications after laparoscopic pancreatoduodenectomy for patients with high risk pancreatic fistula.