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Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage â ¢C and 47 cases (77.0%) classified as stage â £ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Antígeno B7-H1/genética , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Resultado del TratamientoRESUMEN
Objective: To analyze the association between low-frequency variants of ARID1A gene and primary liver cancer using latent category model. Methods: The low-frequency variants of ARID1A gene was combined according to different functional areas, and the combined variables were analyzed by using the latent class model to obtain the latent variables. Then the logistic regression was used to analyze the association between low-frequency variants of ARID1A gene and primary liver cancer. Results: The low-frequency variants of ARID1A gene were divided into three categories by the latent class model. The class 1 was mainly unmutated population, the proportion was 94.2% (2 454/2 603). The class 2 was mainly transcriptional regulatory domain mutation, take 4.8% (124/2 603). The class 3 was dominantly exon mutation, about 1.0% (27/2 603). Using class 1 as a reference, it was found that mutations in the transcriptional regulatory domain could reduce the risk of liver cancer (OR=0.601, 95% CI=0.364-0.992, P=0.046). Conclusion: The latent class model can identify low-frequency variants of gene associated with liver cancer and can be extended to more genetic association studies of low-frequency variants related to complex diseases.
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Neoplasias Hepáticas , Proteínas Nucleares , Proteínas de Unión al ADN , Humanos , Análisis de Clases Latentes , Neoplasias Hepáticas/genética , Mutación , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Sepsis , Animales , Modelos Animales de Enfermedad , Interleucinas , Quinasas Janus , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo , Sepsis/tratamiento farmacológico , Transducción de Señal , Interleucina-22RESUMEN
Objective: To investigate the blood pressure control and its influencing factors in hypertension patients with MS. Methods: Between January 2017 and December 2018, more than 78 000 residents aged 35-75 years selected through convenient sampling were invited to participant in China Patient-Centered Evaluative Assessment of Cardiac Event Million Persons Project in Fujian province, physical and laboratory tests were conducted for them, and their basic information were recorded. A total of 5 281 hypertension patients with MS were included in the study. Results: The treatment rate of hypertension patients with MS was 55.5%, and the control rate was 7.2%. The control rate was higher in patients who were older, women, had advanced education level, had history or family history of cardiovascular disease. The results of multivariate analysis indicated that living area (urban or rural), cardiovascular history, diabetes, urine protein, BMI had impacts on both treatment and control of hypertension. Family history of cardiovascular disease, age, self-management of hypertension, dyslipidemia, waist circumference and drinking had impacts on the treatments, and gender had effects on the control. Conclusions: The treatment rate of hypertension patients with MS was unsatisfactory and the control rate was low. Intervention should be strengthened in rural area, males and young age groups, and activity of self-management group of hypertension should be conducted regularly.
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Hipertensión , Síndrome Metabólico , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/prevención & control , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Factores Socioeconómicos , Resultado del TratamientoRESUMEN
Objective: To summarize the clinical diagnosis and therapeutic method in chronic hepatitis B (CHB) combined with autoimmune hepatitis (AIH). Methods: Clinical manifestations, laboratory examination, imaging, histopathological characteristics, treatment and prognosis of 19 cases diagnosed with CHB combined with AIH followed at the outpatient Department of Gastroenterology of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine during December 2013 to June 2018 were retrospectively analyzed. Paired sample t-test was used before and after treatment for the measurement of normal distribution data. Measurement data of non-normal distribution were expressed as a median (quartile spacing) and Wilcoxon matched-pairs signed rank test was used before and after treatment. Results: Among the 19 cases, 5 were male and 14 were female. The age of onset was 35 to 63 years, and the average age was 47.10 ± 8.76 years. There were 12 cases diagnosed with CHB before AIH, 5 cases diagnosed with AIH before CHB, and 2 cases diagnosed with AIH and CHB at the same time. After the definite diagnosis of CHB combined with AIH, nucleoside (acid) analogues (antiviral against hepatitis B virus) combined glucocorticoid therapy were given, and azathioprine or mycophenolate mofetil (immunosuppressant) was added according to the intrahepatic inflammation (inflammation graded at G3 and above) and leukocyte conditions. The duration of treatment varied between 2 weeks to 16 (median treatment duration of 6 weeks), except for one case who was just diagnosed and followed up. Biochemical indicators and immunoglobulin of the remaining 18 cases before and after treatment was significantly decreased, and the differences were statistically significant (P < 0.05), with HBV DNA < 20 copies/ml. Conclusion: CHB combined with AIH diagnosis can be easily missed. Therefore, it requires comprehensive diagnosis combined with clinical characteristics, autoantibodies, and immunoglobulin levels with special emphasis on pathological characteristics of liver tissue. Anti-HBc-positive patients using immunosuppressant should be carefully monitored for HBV DNA and anti-HBV treatment should be given if necessary.
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Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/terapia , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/terapia , Adulto , China , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis Autoinmune/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Objective: To explore whether combining treatment of chronic obstructive pulmonary disease (COPD) with anti-tumor therapy is better than that of tumor treatment alone in advanced non-small cell lung cancer (NSCLC) patients with COPD in the real world. Methods: The clinical data of 101 patients with advanced NSCLC complicated with COPD from January 1, 2015, to December 31, 2017, in the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively, including 99 males and two females, aged from 52 to 84 years[average (67±8) years]. Among the patients, 90 (89.1%) were smokers, with an average pack-year smoking index of (47±4) . The patients were divided into observation and control groups, depending on whether they received standardized anti-COPD supportive treatment. In the observation group, there were 36 patients, including 35 males and one female, aged from 54 to 84 years[ average (67±8) years], with an average pack-year of smoking (47±4). There were 65 patients in the control group, including 64 males and one female, aged from 52 to 83 years [average (67±8) years], with an average pack-year of smoking 47±4. There was no significant difference in the baseline data between the two groups. The primary outcome measures included the Objective response rate (ORR), disease control rate (DCR), disease-free survival (PFS), and overall survival (OS) of the two groups. An unpaired t-test was used to compare continuous variables between the observation and control groups. The Pearson chi-square test was used to compare categorical variables between the two groups. Kaplan-Meier survival curves were used to evaluate the median PFS and median OS of patients, and the log-rank test was used to assess differences between groups. Result: The ORR of the observation group and the control group was 22.6% (7 cases) and 22.2% (11 cases), respectively, with no significant difference (χ(2)=0.01, P=0.971). The DCR between the observation group and the control group was 58.1% (19 cases) and 57.8% (27 cases), with no significant difference (χ(2)=0.02, P=0.889). Median PFS in the observation group was 6.0 months, which was better than the 3.5 months in the control group (χ(2)=3.947, P<0.05). The median OS of the observation group was 18.0 months, which was better than the 15.0 months of the control group (χ(2)=4.083, P<0.05). Conclusions: Compared with the treatment of tumors alone, combination of anti-tumor therapy with anti-COPD therapy showed longer PFS and OS in patients with advanced NSCLC complicated with COPD.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To explore the relationship of Crohn's disease (CD) susceptibility to aryl hydrocarbon receptor (AhR) polymorphisms and haplotypes in Han population in Wenzhou city, China. Methods: A total of 310 CD patients and 573 age- and sex-matched healthy controls were enrolled in our study. Three single nucleotide polymorphisms (SNPs) of AhR(rs10249788,rs2158041,rs2066853) were determined by the improved multiple ligase detection reaction technique. Unconditional logistic regression analyses was applied to analyze the allelic and genotypic differences of each SNP between CD patients and controls, as well as their influence on the clinicopathologic characteristics in CD patients. Analyses of linkage disequilibrium and haplotype were performed by Haploview 4.2 software in all study subjects. Results: Compared with the controls, the variant allele (T) and genotype (CT+TT) of (rs2158041) were evidently decreased among CD patients (19.52% vs. 25.04%, P=0.009; 34.19% vs. 44.68%, P=0.003). According to "the Montreal Classification Standards" , CD patients were divided into different subgroups. The variant allele (T) and genotype (CT+TT) of (rs2158041) were significantly lower in patients with terminal ileum CD than in controls (16.79% vs. 25.04%, P=0.005; 28.24% vs. 44.68%, P=0.001). Similar conclusions were also drawn in patients with constricting disease when compared with the controls (15.20% vs. 25.04%, P=0.003; 28.43% vs. 44.68%, P=0.003). The three SNPs above were shown to be in a linkage disequilibrium. Compared with the controls respectively, the frequency of haplotype (CCG) was increased in CD patients (44.73% vs. 39.60%, P=0.039), whereas that of haplotype (CTG) was decreased (18.02% vs. 22.78%, P=0.047). Conclusions: AhR (rs2158041) variation might influence the risk as well as the location and behavior of CD. The haplotype (CCG) possibly increase the risk of CD development, whereas haplotype (CTG) might decrease it.
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Pueblo Asiatico/genética , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Hidrocarburo de Aril/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Niño , China , Enfermedad de Crohn/diagnóstico , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO(2) improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion: Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Hipoxia/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Hipoxia/etiología , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pemetrexed/administración & dosificación , Inducción de Remisión , Criterios de Evaluación de Respuesta en Tumores Sólidos , Índice de Severidad de la Enfermedad , Taxoides/administración & dosificación , GemcitabinaRESUMEN
Objective: To explore the association of Crohn's disease (CD) with T cell immunoglobulin and mucin domain 3 (Tim-3) gene polymorphisms in patients of Zhejiang Han population in China. Methods: A total of 308 CD patients and 573 age- and sex-matched healthy controls were enrolled in our study. Two single nucleotide polymorphisms (SNPs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique (iMLDR). Analyses of linkage disequilibrium and haplotype were also performed by Haploview 4.2 software in all study subjects. Results: In general, the allele and genotype frequencies of Tim-3 (rs1036199 and rs10515746) were not statistically different between CD patients and the controls (all P>0.05). According to "the Montreal Classification" , CD patients were divided into different subgroups. The variant allele (C) and genotype (AC+ CC) of rs1036199 were more frequent in CD patients with penetrating diseases than in the controls (10.4% vs 1.7%, P=0.002; 20.8% vs 3.5%, P=0.023). Similar conclusions were also drawn for the variant allele (A) and genotype (CA+ AA) of rs10515746 in patients with penetrating diseases when compared with the controls (10.4% vs 2.2%, P=0.000; 20.8% vs 4.2%, P=0.033, respectively). The two SNPs of Tim-3 were in strong linkage disequilibrium (D'=1.0, r2=0.928). The haplotype (AC) formed by their wild-type alleles (A) and (C) was decreased in patients with penetrating CD compared with the controls (89.6% vs 98.3%, P=0.000). However, the haplotype (CA) formed by their variant alleles was more frequent in patients with penetrating CD than in the controls (10.4% vs 1.6%, P=0.000). Conclusions:Tim-3 (rs1036199 and rs10515746) variations might be correlated with the enhanced risk of penetrating diseases in CD patients. Furthermore, the haplotype (AC) and (CA) formed by the two SNPs might be a protective and a risky factor for penetrating CD respectively.
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Enfermedad de Crohn/genética , Receptor 2 Celular del Virus de la Hepatitis A/genética , Proteínas de la Membrana/genética , Mucina 3 , Linfocitos T/metabolismo , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Enfermedad de Crohn/etnología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunoglobulinas , Polimorfismo de Nucleótido Simple , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
Objective: To investigate the expression of programmed death-1 (PD-1) in liver tissue and its association with liver pathology in patients with autoimmune hepatitis (AIH). Methods: A total of 54 AIH patients (38 in the active stage and 16 in the remission stage) were enrolled, and 9 healthy volunteers were enrolled as control group. Immunohistochemistry combined with quantitative image analysis was used to measure the expression of PD-1 in liver tissue. The t-test, rank sum test, one-way analysis of variance, least significant difference t-test, Mann-Whitney U test, and Pearson relation analysis were used for statistical analysis of different types of data. Results: The AIH group had a significantly higher positive rate of PD-1 in liver tissue than the control group (13.57%±6.84% vs 2.22%±0.66%, P < 0.01), and the patients in the active stage of AIH had a significantly higher positive rate of PD-1 in liver tissue than those in the remission stage (16.53%±7.72% vs 6.56%±3.16%, P < 0.01). The positive rate of PD-1 in liver tissue was 6.56%±3.16% in G0 group, 14.33%±5.08% in G1-2 group, and 19.23%±5.41% in G3-4 group (P < 0.01), but there was no significant difference in the positive rate of PD-1 between S0, S1-2, and S3-4 groups (P > 0.05). In AIH patients, the positive rate of PD-1 in liver tissue was positively correlated with the levels of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and IgG (r = 0.665, 0.721, 0.711, and 0.813, all P < 0.01). Conclusion: AIH patients have regulated PD-1 expression in liver tissue, which is closely associated with liver inflammation and is not associated with fibrosis degree, suggesting that PD-1 is involved in the development and progression of inflammation in AIH patients.
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Aspartato Aminotransferasas/sangre , Hepatitis Autoinmune/metabolismo , Inflamación/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Alanina Transaminasa , Estudios de Casos y Controles , Hepatitis Autoinmune/diagnóstico , Humanos , Receptor de Muerte Celular Programada 1/fisiologíaRESUMEN
Objective: To investigate the association of ulcerative colitis (UC) with fork head/winged helix transcription factor-3 (Foxp3) polymorphisms in Han population in Zhejiang province, China. Methods: A total of 381 UC patients and 490 healthy controls were enrolled in this study.The four single nucleotide polymorphisms (SNPs) of Foxp3 (rs3761547, rs2232365, rs2294021, rs3761548) were examined by SNaPshot.The analyses of linkage disequilibrium (LD) and haplotype were also performed in all study subjects. Results: When male and female UC patients were compared with their corresponding controls respectively, the alleles and genotypes of the four SNPs were not statistically different (all P>0.05). According to severity and location of the disease, the UC patients were divided into different subgroups. The alleles (C, G, A) of (rs2232365, rs2294021, rs3761548) were more frequent in male patients with severe UC than in the male controls (69.6% vs 34.3%, P=0.001; 69.6% vs 34.3%, P=0.001; 39.1% vs 14.4%, P=0.002, respectively). As compared with the female controls, the alleles (C, G, A) and genotypes (TC+ CC, AG+ GG, CA+ AA) of (rs2232365, rs2294021, rs3761548) were significantly increased in the female patients with severe UC (51.9% vs 38.0%, 63.5% vs 39.2%, 53.8% vs 21.4%, 80.8% vs 57.7%, 84.6% vs 58.4%, 76.9% vs 34.7%, all P<0.05). The four SNPs above were shown to be in a strong LD both in male and in female subjects.When male and female UC patients were compared with their corresponding controls respectively, nevertheless, each haplotype frequency was not statistically different (all P>0.05). Conclusions:Foxp3 (rs2232365, rs2294021, rs3761548) variations might engender the increased risk of severe UC in Chinese Han patients.
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Pueblo Asiatico/genética , Colitis Ulcerosa/genética , Factor de Transcripción 3/genética , Factores de Transcripción Winged-Helix/genética , Adulto , Alelos , China , Colitis Ulcerosa/etnología , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To investigate the association of Crohn's disease (CD) with transcobalamin â ¡ (TCN2) gene polymorphisms and serum homocysteine (Hcy), folate, and vitamin B12 levels in Chinese patients. METHODS: In a total of 307 CD patients (CD group) and 574 healthy controls (control group) of Han ethnicity selected at 4 hospitals in Wenzhou between January 2007 and August 2015, TCN2 gene polymorphisms (rs1801198, C/G; rs9606756, A/G) in peripheral blood were determined using improved multiple ligase detection reaction (iMLDR). The Simplified Crohn's Disease Activity Index (CDAI) was applied to evaluate activity of CD. Eighty-eight CD patients and 138 age- and sex-matched controls were randomly selected from all the study subjects using computer-generated random numbers, in whom serum Hcy level was tested by enzymatic cycling assay, folate and vitamin B12 levels were examined by chemiluminescence immunoassay. RESULTS: (1) The mutant allele (G) and genotype (CG+ GG) of rs1801198 were not significantly different between the CD group and the control group (both P>0.05), but more prevalent in patients with stricturing CD than in controls (65.75% vs 56.10%, 93.15% vs 82.40%, both P<0.05). The frequencies of mutant allele (G) and heterozygous genotype (AG) of rs9606756 were higher in CD patients than in controls (2.44% vs 1.05%, 4.89% vs 2.09%, both P<0.05), also higher in patients with stricturing CD or ileocolonic CD compared with controls (stricturing CD: 4.79% vs 1.05%, 9.59% vs 2.09%; ileocolonic CD: 3.18% vs 1.05%, 6.36% vs 2.09%; all P<0.05). The two polymorphic loci (rs1801198 and rs9606756) were shown to be in a weak linkage disequilibrium. The frequency of haplotype (GG) was higher in the CD patients than in the controls (2.23% vs 0.81%, P<0.05). (2) When compared with the controls, the serum Hcy level was higher in the CD patients (P=0.023), whereas the folate and vitamin B12 levels were decreased in the CD patients (both P<0.001). The prevalence of hyperhomocysteinemia (Hcy >15 µmol/L), folate deficiency (folate <4 µg/L) and vitamin B12 deficiency (<203 ng/L) were higher in the CD patients than in the controls (18.18% vs 4.35%, 27.27% vs 5.07%, 31.82% vs 5.07%, all P<0.01). Compared to the patients at remission stage (CDAI<5), the serum Hcy level was increased in those at active stage (CDAI≥5) (P=0.005), while the folate and vitamin B12 levels were decreased in the patients ate active stage (both P<0.05). (3) According to the results of multivariate linear regression analysis, average Hcy level in the CD patients was negatively associated with folate level (ß=-0.494, P<0.001), while positively correlated with percentage of neutrophils (ß=0.294, P=0.004). Unconditional Logistic regression showed that both folate deficiency and vitamin B12 deficiency were independent risk factors for CD (OR=5.415, OR=7.112, both P<0.001). CONCLUSIONS: TCN2 rs1801198 mutation might be associated with increased risk of stricturing CD. TCN2 rs9606756 mutation might be a potential functional locus to affect CD susceptibility. Individuals carrying the haplotype (GG) formed by TCN2 (rs1801198 and rs9606756) seem to be at higher risk of developing CD. Hyperhomocysteinemia, folate deficiency, and vitamin B12 deficiency are prevalent in this cohort of CD patients of Han ethnicity from Zhejiang province. Both folate deficiency and vitamin B12 deficiency are independent risk factors for CD.
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Enfermedad de Crohn , Polimorfismo Genético , Alelos , Ácido Fólico , Deficiencia de Ácido Fólico , Genotipo , Haplotipos , Heterocigoto , Homocisteína , Humanos , Hiperhomocisteinemia , Mutación , Prevalencia , Factores de Riesgo , Transcobalaminas , Vitamina B 12 , Deficiencia de Vitamina B 12RESUMEN
Objective: To understand the underreporting of death cases and related factors in disease surveillance system of Fujian province. Methods: We carried out a field underreporting survey in 20 disease surveillance sites selected through stratified cluster random sampling during 2012-2014. The related factors of underreporting were analyzed by using logistic regression method. Propensity score weighting method was used to calculate the underreporting rate in different groups classified by year, urban/rural areas, gender, age and death cause variables. Results: The overall underreporting rate was 9.21%(95%CI: 9.06%-9.39%) after adjusting by propensity score weighting method. The underreporting rate was higher in rural area (11.55%, 95%CI: 11.30%-11.81%) than in urban area (6.64%, 95%CI: 6.50%-6.78%). The underreporting rate was highest in age group 0-14 years (36.29%, 95% CI: 34.23%-38.67%) and lowest in age group ≥65 years (7.91%, 95% CI: 7.78%-8.03%). The underreporting rate was higher in people died of perinatal disease, congenital anomalies and injury. Conclusion: The underreporting rates were different between different groups classified by urban/rural areas, age and death cause variables. Propensity score weighting method can be used to adjust underreporting rate of death cases in mortality surveillance in Fujian.
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Causas de Muerte , China , Humanos , Puntaje de Propensión , Población Rural , Población UrbanaRESUMEN
OBJECTIVE: To evaluate the patterns, related factors and prognostic value of abnormal magnetic resonance angiography (MRA) in human immunodeficiency virus negative tuberculous meningitis. MATERIALS AND METHODS: We performed a prospective study in patients aged >14 years. Abnormality on MRA was correlated with clinical, laboratory and magnetic resonance imaging findings. Modified Barthel index was used to assess outcome at 6 months after inclusion. RESULTS: Of 101 patients included, MRA was abnormal in 45 (44.6%). The distribution of MRA abnormality was classified as disseminated irregular calibres of intracranial arteries with or without reduction in distant branches (29.7%, pattern 1) and localised stenosis at the base of the brain (26.7%, pattern 2). In logistic regression analysis, pattern 2 was related to stage of the disease (P = 0.002), basal exudates (P = 0.03) and infarction (P = 0.000), while pattern 1 was related to duration of disease (P = 0.050), hydrocephalus (P = 0.032) and age (P = 0.002). Pattern 1 was also correlated with infarction (P = 0.000), particularly infarction in the tubercular zone (P = 0.035) in univariate analysis. MRA abnormality was associated with paradoxical worsening (P = 0.022) and poor prognosis in univariate analysis (P = 0.035). CONCLUSION: MRA abnormality is associated with stroke and poor outcomes. Although it indicates mild vascular injury, pattern 1 MRA abnormality is nevertheless associated with infarction and needs proper intervention.
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Hidrocefalia/diagnóstico , Angiografía por Resonancia Magnética , Accidente Cerebrovascular/complicaciones , Tuberculosis Meníngea/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Constricción Patológica/diagnóstico , Femenino , Seronegatividad para VIH , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: The precise etiology of inflammatory bowel diseases (IBDs) is still unknown although dysregulation of apoptosis likely plays an important role in this pathogenesis. However, the significance of mucosal T-cell apoptosis in ulcerative colitis (UC) is unclear. In the present work we investigated the role of TNF-related apoptosis-inducing ligand (TRAIL), which is implicated in various human disorders. PATIENTS AND METHODS: Results from a total of 393 UC patients and 1292 healthy individuals were analyzed in this study. We determined the three single nucleotide polymorphisms of TRAIL in 3' untranslated regions (UTR), and examined the plasma soluble TRAIL (sTRAIL) levels by enzyme-linked immunosorbent assay. RESULTS: We found that the mutant genotypes of TRAIL (G1525A/G1588A/C1595T and G1525A and G1588A) were much lower in UC patients compared to the controls. Furthermore, mutant allele and genotype of TRAIL C1595T were more prevalent in severe UC patients than in other patients (p < 0.001; p = 0.005, respectively). The three polymorphic sites in 3'UTR were in a perfect linkage disequilibrium in our study. In contrast to controls, the GAT haplotype was increased (p < 0.001), while the AAT haplotype was decreased in UC patients (p < 0.001). Besides, the plasma levels of sTRAIL were significantly higher in UC patients than in controls (p < 0.001). CONCLUSIONS: Our findings suggested that increased occurrence of the genetic mutations of TRAIL in 3'UTR and possibly decreased plasma levels of sTRAIL might lead to a lower risk of UC attack in Chinese patients.
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Pueblo Asiatico/genética , Colitis Ulcerosa/genética , Estudios de Asociación Genética , Polimorfismo Genético/genética , Vigilancia de la Población , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Adulto , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Femenino , Estudios de Asociación Genética/métodos , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Ligando Inductor de Apoptosis Relacionado con TNF/sangreRESUMEN
UNLABELLED: To reduce the cost of bacterial cellulose (BC) production, the possibility of using acetone-butanol-ethanol (ABE) fermentation wastewater with high COD value (18 050 mg l(-1) ) for BC production by Gluconacetobacter xylinus was evaluated. After 7 days of fermentation, the highest BC yield (1·34 g l(-1) ) was obtained. The carbon sources including sugars (glucose and xylose), organic acids (acetic acid and butyric acid) and alcohol compounds (ethanol and butanol) were utilized by G. xylinus simultaneously during fermentation. Although the COD decrease ratio (about 14·7%) was low, the highest BC yield on COD consumption (56·2%, g g(-1) ) was relatively high and the remaining wastewater could be used for further BC fermentation. Besides, the environment of ABE fermentation wastewater showed small influence on the BC structure by comparison with the BC products obtained in traditional HS medium using field emission scanning electron microscope (FE-SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Overall, ABE fermentation wastewater is one promising substrate for BC production. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of using acetone-butanol-ethanol (ABE) fermentation wastewater for bacterial cellulose (BC) production by Gluconacetobacter xylinus was evaluated in this study. This is the first time that ABE fermentation wastewater was used as substrate for BC fermentation. The results provide detail information of metabolism of G. xylinus in ABE fermentation wastewater and the influence of wastewater environment on the structure of BC samples. Overall, this bioconversion could reduce the cost of BC production greatly.
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Celulosa/biosíntesis , Fermentación/fisiología , Gluconacetobacter xylinus/metabolismo , Aguas Residuales/microbiología , Ácido Acético/metabolismo , Acetona/metabolismo , Butanoles/metabolismo , Ácido Butírico/metabolismo , Carbono/metabolismo , Celulosa/metabolismo , Etanol/metabolismo , Glucosa/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Xilosa/metabolismoRESUMEN
OBJECTIVE: The aim of the present study was to investigate the presence of anti-Chlamydia pneumoniae (Cp) antibodies in patients with ankylosing spondylitis (AS) to determine whether there is an association with AS disease activity. METHODS: Seventy-nine AS outpatients and 73 normal controls were enrolled in this case-control study. Serum anti-Cp immunoglobulins (CpIg) were detected by enzyme-linked immunosorbent assay (ELISA). Antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Chlamydia trachomatis (Ct) were also measured. Clinical and experimental data were collected, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was determined. Patients with positive Cp IgM or Cp IgA were considered to have had a recent Cp infection. RESULTS: Cp IgG was detected in the majority of AS patients and also controls (88.8% vs. 91.8%, respectively). The seroprevalence of Cp IgA and Cp IgM was significantly higher in AS patients than in the controls (51.9% vs. 31.5%, p = 0.010 for Cp IgA; 79.7% vs. 20.5%, p < 0.0001 for Cp IgM). Seropositivity of Cp IgM was associated with elevation of the disease activity index, including erythrocyte sedimentation rate (ESR; p = 0.021), C-reactive protein (CRP; p = 0.007) and the BASDAI (p = 0.009). Persistent positive Cp IgM was associated with active disease, while seroreversion of Cp IgM was associated with a reduction in these disease activity indices. There was no correlation between Cp IgM or Cp IgA and symptomatic upper respiratory infections or other clinical manifestations. CONCLUSIONS: Recent Cp infections occur frequently in AS patients and Cp IgM antibody is correlated with active disease. These findings indicate that Cp infections may be a triggering factor for active AS.
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Pueblo Asiatico , Infecciones por Chlamydia/etnología , Infecciones por Chlamydia/epidemiología , Chlamydophila pneumoniae , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/etnología , Espondilitis Anquilosante/epidemiología , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Estudios de Casos y Controles , China , Infecciones por Chlamydia/inmunología , Chlamydia trachomatis/inmunología , Chlamydophila pneumoniae/inmunología , Estudios de Cohortes , Comorbilidad , Citomegalovirus/inmunología , Femenino , Herpesvirus Humano 4/inmunología , Humanos , Masculino , Espondilitis Anquilosante/inmunologíaRESUMEN
A new sample introduction method of capillary electrophoresis, in which field-amplified sample injection was combined with a pre-concentration of non-uniform field electrophoresis, is presented in this paper. With an additional pre-concentration voltage applied to sample solution, a non-uniform electric field was generated, with which analytical cations or anions were pre-concentrated around an electrode adjacent to the injection end of capillary. After the pre-concentration, analytical ions were injected into the capillary and stacked at the boundary between sample and buffer solution inside capillary by field-amplified injection technique. In contrast to the conventional field-amplified injection, larger concentration factor and higher analytical sensitivity were obtained with the improved pre-concentration method. Its concentration factor was about 10 approximately 15 fold as that of field-amplified sample injection.