Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 832
Filtrar
1.
Front Immunol ; 13: 870406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572526

RESUMO

Maintenance therapy is rarely considered in pancreatic ductal adenocarcinoma (PDAC). We describe the case of a 57-year-old man with metastatic PDAC treated with an initially full but subsequently de-escalated dose of combination chemotherapy due to intolerance to neurotoxicity. After a complete response to combined radiofrequency ablation for the liver metastasis and radiotherapy for the pancreatic tumor was achieved, chemotherapy was terminated and maintenance therapy was applied: nivolumab plus cytokine-induced killer cell therapy initially and then a de-escalated dosing interval of nivolumab monotherapy subsequently. No adverse events occurred during nivolumab therapy for more than 2 years, and the patient remains disease-free. To date, this is the first report of maintenance nivolumab after successful multimodality therapy in metastatic PDAC.

2.
Infect Genet Evol ; 101: 105293, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504588

RESUMO

Mitochondria are essential for hepatitis B virus (HBV) infection. Moreover, the findings of our previous study indicate that host mitochondrial genetic factors are associated with chronic hepatitis B (CHB) for the Han Chinese. However, in terms of genetic heterogeneity, the impact of mitochondria on host susceptibility to HBV infection in ethnic minorities in China remains unclear. Here, a total of 7070 subjects who had visited the hospital between June 1, 2019, and April 31, 2020, were enrolled for seroprevalence of HBV infection investigation. A total of 220 individuals with CHB (CHBs) and 223 individuals with a trace of HBV infection (spontaneously recovered subjects, SRs) were analyzed for mitochondrial DNA (mtDNA) sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between CHBs and SRs. Among eight nationalities, Yi nationality patients had the highest HBsAg prevalence rate (27.9% [95% CI: 25.3%-30.5%]) and the lowest vaccination rate (4.9% [95% CI: 3.7%-6.2%]). After adjustment for age and gender, haplogroup F was a risk factor for CHB infection (P = 0.049, OR = 2.079, 95% CI = 1.002-4.31), while D4 had a significant negative correlation with the HBeAg-positive rate (P = 0.024, OR = 0.215, 95% CI = 0.057-0.816). Together with our previous study, the findings indicate that different nationalities have different genetic susceptibility to HBV infection.

3.
Am J Cancer Res ; 12(4): 1884-1898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530292

RESUMO

Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (NalFL) comprises the current standard for gemcitabine-failed metastatic pancreatic ductal adenocarcinoma (PDAC). As liposomes generally accumulate in the spleen, we evaluated the impact of spleen volume on prognosis. We enrolled patients with metastatic PDAC who failed gemcitabine-based therapy and were initiated on NalFL between August 2018 and November 2020. The spleen volume before NalFL administration was evaluated. They were stratified into dose subgroups (i.e. low, < 48 mg/m2; intermediate, 48 - < 64 mg/m2; high, ≥ 64 mg/m2) by the average nal-IRI dose during the entire treatment, and multivariate analysis of overall survival (OS) was performed. We included 547 patients with a median age of 63 years (range, 27-89 years) and a median of 1 (range, 0-7) palliative chemotherapy regimen. The median spleen volume was 245 mL (range, 82-817 mL). Among patients with splenomegaly (≥ 245 mL), the low-dose subgroup had the worst median time to treatment failure (TTF, 1.8 months vs. 2.5 months vs. 2.5 months, P = 0.020) and OS (3.3 months vs. 5.9 months vs. 6.6 months, P = 0.018) as against no prognostic impact in patients without splenomegaly. In the multivariate analysis of patients with splenomegaly, performance status (PS) ≥ 2, body surface area (BSA) < 1.6 m2, prior fluoropyrimidine use, liver metastasis, and low-dose subgroup were independent poor prognostic factors. A low average nal-IRI dose was significantly associated with poor prognosis, especially among patients with splenomegaly. Further pharmacological studies should validate the relevance of spleen volume on the treatment outcomes of nal-IRI.

4.
Front Pharmacol ; 13: 887598, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600888

RESUMO

Background: Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterification of aspirin with eugenol using the prodrug principle. AEE has the pharmacological activities of being anti-inflammatory, antipyretic, analgesic, anti-cardiovascular diseases, and anti-oxidative stress However, its oral bioavailability is poor, and its intestinal absorption and transport characteristics are still unknown. Objective: The purpose of this study was to investigate the uptake and transport mechanisms of AEE in Caco-2 cells. Methods: The effects of time, concentration, and temperature on the transport and uptake of AEE were studied. Results: The results showed that a higher concentration of salicylic acid (SA) was detected in the supernatant of cell lysates and cell culture medium, while AEE was not detected. Therefore, the content change of AEE was expressed as the content change of its metabolite SA. In the uptake experiment, when the factors of time, concentration, and temperature were examined, the uptake of SA reached the maximum level within 30 min, and there was concentration dependence. In addition, low temperature (4°C) could significantly reduce the uptake of SA in Caco-2 cells. In the transport experiment, under the consideration of time, concentration, and temperature, the transepithelial transport of SA from AP-BL and BL-AP sides was time-dependent. The amount of SA transported in Caco-2 cells increased with the increase of concentration, but the transmembrane transport rate had no correlation with the concentration. This phenomenon may be due to the saturation phenomenon of high concentration. The efflux ratio (ER) was less than 1, which indicated that their intestinal transport mechanism was passive transport. Moreover, the temperature had a significant effect on the transport of AEE. Conclusion: In summary, intestinal absorption of AEE through Caco-2 cell monolayers was related to passive transport. The uptake and transport of AEE were concentration-dependent, and temperature significantly affected their uptake and transport. The absorption and transport characteristics of AEE may contribute to the exploration of mechanisms of absorption and transport of chemosynthetic drugs in vitro.

5.
Vet Microbiol ; 269: 109420, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35533579

RESUMO

The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) variants represents a threat to public health. tet(X4) is highly endemic in northwestern China. Here, we extended the region to western China to further understand its epidemiology and distribution. During 2018-2020, 1497 faecal samples from pigs, sheep and goats in western China were screened for tet(X4)-positive strains. A total of 134 tigecycline-nonsusceptible Escherichia coli were isolated; among them, the largest number were isolated from Guangxi (66.42%, 89/134), Shaanxi (17.16%, 23/134) and Ningxia (8.21%, 11/134). Antibiotic susceptibility testing showed that all of these isolates were multidrug-resistant bacteria that were also resistant to florfenicol. Eighty-nine of 134 tet(X4)-positive Escherichia coli were analysed by whole-genome sequencing. They belonged to twenty-seven sequence types, and ST10, ST48, ST189 and ST2223 were the main types of Escherichia coli. Seventy-six of the 134 tet(X4)-positive Escherichia coli could transfer tet(X4) into the recipient Escherichia coli 26 R 793. Southern blot analysis showed that there were multiple plasmids carrying the tet(X4) gene in a single strain. The plasmids of the 89 tet(X4)-bearing isolates in this study were analysed. tet(X4)-bearing plasmids ranged from 20 to 400 kb, and the main plasmid types were categorised as IncX1, IncY, and ColRNAI. Guangxi, Ningxia, and Shanxi are likely to be the seminal and most affected areas. Additional efforts are needed to evaluate the impact of the spread of these tigecycline resistance genes and tigecycline-resistant isolates.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Doenças dos Ovinos , Doenças dos Suínos , Animais , Antibacterianos/farmacologia , China/epidemiologia , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Testes de Sensibilidade Microbiana/veterinária , Plasmídeos/genética , Ovinos , Suínos , Doenças dos Suínos/epidemiologia , Tigeciclina/farmacologia
6.
Front Genet ; 13: 836431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464850

RESUMO

Type 3 hereditary hemochromatosis (HH) is a rare form of HH characterized by genetic mutation in the TFR2 gene. Clinical features reported in patients with type 3 HH include abnormal liver function, liver fibrosis, cirrhosis, diabetes, hypogonadism, cardiomyopathy, and skin pigmentation. Since its original description in 2000, 33 pathogenic TFR2 mutations associated with HH have been described until now. Here, we first reported a Chinese pedigree of TFR2-related hemochromatosis with a novel compound heterozygous mutation c.1288G > A (p.G430R)/c.960T > A (p.Y320X). Interestingly, different phenotypes were reported although the proband and his sister shared the same gene mutation. This inconsistency between genotypes and phenotypes indicates multifactorial etiology contributing to the development of HH. Our report broadens the mutation spectrum of the TFR2 gene associated with HH.

7.
Cancer Cell Int ; 22(1): 145, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392906

RESUMO

BACKGROUND: This study aimed to observe the effect of transient receptor potential canonical channel 6 (TRPC6) antagonist 1-(ß-[3-(4-method-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrate (SKF-96365) and its agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) on the proliferation of cervical cancer cell lines HeLa and SiHa, deoxyribonucleic acid (DNA) synthesis, cell migration, and TRPC6 expression. METHOD: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of TRPC6 in HeLa and SiHa cells. The tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the 5-ethynyl -2'- deoxyuridine (EdU) fluorescence detection assay, and a scratch test were used to detect the changes of proliferation, DNA synthesis and cell migration of HeLa and SiHa cells after SKF 96,365 and OAG acted on HeLa and SiHa cells for different lengths of time. RT-qPCR was used to detect expression changes of TRPC6 SKF-96365 and OAG treated HeLa and SiHa cells. RESULTS: TRPC6 was expressed both in HeLa and SiHa cells. The MTT assay showed that after 24 h of SKF-96365 treatment, compared with the control group, the proliferation of HeLa and SiHa cells was inhibited, and there was a statistically significant difference (p < 0.05). After 24 h of OAG, compared with the control group, the proliferation of HeLa and SiHa cells had increased, and there was a statistically significant difference (p < 0.05). EdU fluorescence detection showed that SKF-96365 could inhibit the DNA synthesis of HeLa and SiHa cells, and OAG could promote the DNA synthesis of HeLa and SiHa cells (p < 0.05) in HeLa and SiHa cell lines. CONCLUSION: The high expression of calcium channel TRPC6 in HeLa and SiHa tissues may be related to the malignant behavior of cervical cancer cell lines HeLa and SiHa. This calcium channel may be a new target for the prevention and treatment of cervical cancer.

8.
Front Chem ; 10: 862007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402389

RESUMO

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a sensitive surface analytical technology, which can simultaneously acquire diverse chemical components and their precise locations on the surfaces of samples without any requirements for chemical damage pretreatments or additional matrices. Commonly, the quality control of TCMs (traditional Chinese medicines) is limited by the qualitative and quantitative evaluations of the specifically extractive constituents. In this study, a practical sample preparation strategy named two-layered media embedding sample preparation was developed to obtain ideal freezing sections of dried materials of Cordyceps sinensis. Meanwhile, the well-established sample preparation method was applied for in situ chemical profiling and imaging of natural (NCS) and cultured Cordyceps sinensis (CCS) by using TOF-SIMS. More than 200 components were tentatively identified and imaged in NCS and CCS at the same time. Mass spectrometry imaging revealed that most components have even distributions in caterpillars of Cordyceps sinensis, while TAGs, DAGs, MAGs, and FAs only have distributions outside caterpillars' digestive chambers. This is the first time that components were in situ imaged for Cordyceps sinensis to exhibit the chemical distributions which have never been achieved by other analytical techniques so far. In addition, chemometrics was used to simplify and explain the massive TOF-SIMS mass data sets, which revealed the high chemical similarity between CCS and NCS. Furthermore, the relative quantification of TOF-SIMS data showed that CCS has comparable proportions of amino acids, nucleosides, monosaccharides, sphingolipids, sterols and other principles to NCS except for fatty acids, glycerides and glycerophospholipids. The higher amounts of TAGs and DAGs in CCS were confirmed by quantitative 1H-NMR, indicating reliable relative quantification of TOF-SIMS. In general, our research developed a novel approach of TOF-SIMS for in situ chemical analysis of TCMs, and its successful application in comparative study of CCS and NCS suggested that TOF-SIMS is an advanced and promising analytical technology for the research of TCMs.

9.
Front Psychol ; 13: 793483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360560

RESUMO

Student-teacher relationships (STRs) have been examined by many studies. However, an omission still exists, the existing scales are not appropriate for studying STRs in private colleges because of the special character of these schools. This paper presents the development and validation of Private-College Student-Teacher Relationship Scale (PCSTRS), the first instrument to evaluate student-teacher relationships (STRs) in private colleges. The PCSTRS has six dimensions: trust, interaction, intimacy, care, approval, and comfort. In our main study, the validity and reliability of the six-factor PCSTRS model were demonstrated. The result of internal consistency coefficient indicated the high reliability of the scale, and the result of concurrent validity indicated the significant correlational relationships between the PCSTRS with other STR measures. In supplementary study, the PCSTRS was administered to 360 participants to confirm the applicability of PCSTRS and investigate the relation of STRs and students' traits, performance, and wellbeing, as well as the differences between the private school and the public school in this relation; the analyses revealed that there were significant differences in trust, intimacy, and care between private and public colleges; positive correlations were found between STRs and self-esteem, self-efficacy, academic performance, extracurricular activity involvement, and subjective wellbeing. Present research firstly develops the PCSTRS, examined the reliability and validity, and provides the proposed nomological network among related constructs.

10.
J Viral Hepat ; 29(6): 420-431, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35274400

RESUMO

This study evaluated the predictive value of serum HBV DNA, HBV RNA, HBcrAg, HBsAg, intrahepatic HBV DNA and cccDNA for HBeAg clearance and seroconversion during long-term treatment with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). A single centre, prospective cohort of CHB patients was used for this study. Serum HBV RNA levels were retrospectively measured at baseline, 6, 12, 24, 36, 48, 60, 72 and 84 months post-NAs treatment. Serum HBsAg and HBcrAg levels were quantified at baseline, month 6, 60 and 72. Histological samples from liver biopsy at baseline and month 60 were analysed for intrahepatic HBV DNA and cccDNA. Eighty-three HBeAg-positive patients were enrolled with a median follow-up time of 108 months (range 18-138 months). Of them, 53 (63.86%) patients achieved HBeAg clearance, and 37 (44.58%) achieved HBeAg seroconversion. Cox multivariate analysis showed that only baseline HBV RNA was independently associated with HBeAg clearance and seroconversion (<5.45 log10 copies/mL, HR = 5.06, 95% CI: 1.87-13.71, p = .001; HR = 3.38, 95% CI: 1.28-8.91, p = .01). The independent association with HBeAg clearance and seroconversion remained for HBV RNA levels at month 6 (<4.72 log10 copies/mL, HR = 4.16, 95% CI: 1.61-10.72, p = .003; HR = 6.52, 95% CI: 1.85-22.94, p = .003) and month 12 (<4.08 log10 copies/mL, HR = 3.68, 95% CI: 1.96-6.90, p < .001; HR = 2.79, 95% CI: 1.31-5.94, p = .008). The AUCs of baseline HBV RNA for predicting the HBeAg clearance (0.83, 95% CI: 0.70-0.96, 0.83, 95% CI: 0.70-0.96 and 0.82, 95% CI: 0.69-0.95 respectively) and seroconversion (0.89, 95% CI: 0.77-1.00; 0.81, 95% CI: 0.66-0.95 and 0.84, 95% CI: 0.71-0.98 respectively) at month 36, 60 and 84 were higher than those of HBV DNA, HBsAg and HBcrAg. In conclusion, lower serum HBV RNA at baseline, month 6 and 12 post-NAs treatment could predict HBeAg clearance and seroconversion during long-term NAs treatment.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Estudos Prospectivos , RNA , Estudos Retrospectivos , Soroconversão
12.
Crit Rev Food Sci Nutr ; : 1-19, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234534

RESUMO

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

13.
Front Oncol ; 12: 853801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311112

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans' Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery. Clinical Trial Registration Number: ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35182031

RESUMO

BACKGROUND: Recent studies have suggested the suboptimal efficacy of liposomal irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) patients previously treated with conventional irinotecan. This study investigated the effect of conventional irinotecan treatment in mPDAC patients receiving nal-IRI+5-FU/LV by analyzing a population-based dataset. METHODS: We reviewed 667 consecutive mPDAC patients treated with nal-IRI+5-FU/LV between August 2018 and November 2020 at Taiwanese medical centers. Eighty-six patients previously treated with conventional irinotecan were matched to 86 patients not treated with conventional irinotecan, following propensity matching for age, sex, performance status, metastatic organ site, pre-treatment carbohydrate antigen 19-9 level, lines of prior chemotherapy treatment, and time from first-line treatment to nal-IRI+5-FU/LV therapy. RESULTS: The median overall survival and time-to-treatment failure were 4.8 and 2.6 vs 4.1 and 2.1 months, respectively, for patients who were and were not previously treated with conventional irinotecan. The tumor response and disease control rates were 5.8% and 32.6% vs 5.8% and 37.2%, respectively, for patients previously treated and not treated with conventional irinotecan. No significant differences were observed in survival times and tumor response rates between the two groups. CONCLUSIONS: Previous conventional irinotecan treatment does not compromise the efficacy of subsequent nal-IRI+5-FU/LV treatment in mPDAC patients.

15.
Ren Fail ; 44(1): 224-232, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35166181

RESUMO

BACKGROUND: Cardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration. METHODS: We conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography. RESULTS: ESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification. CONCLUSIONS: CVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.


Assuntos
Calcinose/sangue , Doenças das Valvas Cardíacas/sangue , Hemodiafiltração , Falência Renal Crônica/terapia , Idoso , Calcinose/etiologia , Cálcio/sangue , China , Estudos Transversais , Ecocardiografia , Feminino , Doenças das Valvas Cardíacas/etiologia , Humanos , Falência Renal Crônica/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
16.
Int J Hematol ; 115(5): 704-712, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35212915

RESUMO

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucopenia , Trombocitopenia , Antineoplásicos/efeitos adversos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucopenia/induzido quimicamente , Cromossomo Filadélfia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Taiwan/epidemiologia , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
17.
Sci Total Environ ; 826: 154010, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35218833

RESUMO

BACKGROUND: Mobile tigecycline-resistance gene tet(X) variants have emerged as diverse pathogens from animal, human as well as their associated environments, which could potentially threaten public health. The insertion sequence, ISCR2, carries tet(X4) for horizontal transfer by rolling-cycle (RC) transposition. However, the diversity of ISCR2 and tet(X4) isolated from different sources is largely unknown. METHODS: The tet(X4)-carrying isolates were collected from human and livestock in several multiple regions of China. The whole genomic sequences of these isolates were either obtained from NCBI GenBank or determined by Illumina Hiseq 2500 and the MinION platform. The intact transposon region, ISCR2-tet(X4)-ISCR2, observed in a small number of isolates as the reference sequence to construct the transposon phylogeny. The diversity of the genetic environments of all ISCR2-tet(X4) elements were analyzed. RESULTS: A 2760-bp element encompassing the tet(X4)-hydrolase-encoding gene, catD, located between two ISCR2 elements was highly conserved in all isolates and could form an RC transposable unit (RC-TU). ISCR2 could also capture more resistance genes and formed a larger RC-TU base on RC transposition. However, the ISCR2-mediated RC-TUs were constantly truncated and inserted by other IS elements, indicating frequent recombination events. Of these elements, IS26 disrupted both the upstream and downstream ISCR2-mediated RC-TUs, indicating that IS26 captured tet(X4), thus leading to a wider spread of tet(X4). CONCLUSIONS: These results confirmed the critical role of ISCR2 for dissemination and co-transmission of tet(X4) and other resistance genes. More effort is needed to monitor the variation tendencies of tet(X4)-carrying mobile elements and determine the driving factors for disseminating transferable tigecycline resistance.


Assuntos
Antibacterianos , Escherichia coli , Animais , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Plasmídeos , Tigeciclina
18.
J Leukoc Biol ; 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35188700

RESUMO

Primary bile acids (BAs), products of cholesterol metabolism and clearance, are synthesized in the liver and released into the intestine to facilitate the digestion and absorption of lipids. BAs are further converted by gut commensal bacteria into secondary colonic BAs and the metabolism disorder is closely linked to cholestatic liver diseases via regulating immune response. However, the effect and underlying mechanism of these host-microorganism biliary metabolites on T lymphocyte remain unclear. In the current study, we synthesized a sulfated product of lithocholic acid (LCA), lithocholic acid 3-sulfate (LCA-3-S), and investigated the binding affinity of the BAs metabolites on RORγt, the transcription factor of IL-17A. Our results demonstrated that the sulfate of LCA, LCA-3-S, exhibited better effect than its oxidated metabolite, 3-oxo-LCA, binding to RORγt. The results further demonstrated that LCA-3-S selectively suppressed Th17 cell differentiation without influence on Th1, Th2, and Treg cells. Collectively, we synthesized the sulfated biliary metabolite LCA-3-S and demonstrated that LCA-3-S selectively inhibited Th17 cell differentiation by targeting RORγt, indicating that metabolite disorder of BAs resulting in the decrease of LCA-3-S probably contributes to the pathogenesis of cholestatic liver diseases.

19.
PeerJ ; 10: e12968, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198264

RESUMO

Grain filling affects grain weight and quality and is among the most critical factors in determining the yield and quality of cereal crops. Though hybrids have larger panicles and numerous spikelets with a larger sink capacity than conventional varieties, data on the grain filling commonalities and differences between foxtail millet varieties with different panicle types remain sparse. In this study, we found that "Zhang Gu 13" (ZG, large panicle) exhibits a significantly higher panicle weight than "Yu Gu 18" (YG, conventional panicle) at the early stage of grain filling, but the weight of YG increased rapidly and gradually overtook ZG during the middle stages. A temporal expression pattern analysis demonstrated that the genes involved in photosynthesis, metabolic pathways, and phenylpropanoid biosynthesis were downregulated, while those related to peroxisome function, purine metabolism, and zeatin biosynthesis were upregulated during grain filling in both varieties. A total of 6,832 differentially expressed genes (DEGs) were identified in both varieties, with the majority identified at the early and late stages. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further revealed that the upregulated DEGs in YG were associated with gibberellin (GA) biosynthesis, ATP-binding cassette (ABC) transporters, and plant hormone signal transduction. Photosynthesis-related DEGs, such as photosystem and antenna proteins, were significantly upregulated in ZG. This study provides preliminary insights into the differences in gene expression and molecular mechanisms of grain filling between ZG and YG in the North China summer-sowing region.

20.
Taiwan J Obstet Gynecol ; 61(1): 96-101, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35181055

RESUMO

OBJECTIVE: To investigate whether genomic instability (GI)-derived long non-coding RNAs (lncRNAs) have a prognostic impact on the patients with endometrial cancer. MATERIAL AND METHODS: Patients with Uterine Corpus Endometrial Carcinoma (UCEC) were selected from The Cancer Genome Atlas (TCGA) database. Systematic bioinformatics analyses were performed, including Pearson correlations, GO and KEGG enrichment analysis, bivariate and multiple logistic regression analysis, and Kaplan-Meier (KM) method. RESULTS: A total of 552 UCEC samples were included in the study. The differentially expressed lncRNAs (DELs) were identified, including 79 down-regulated lncRNAs and 31 up-regulated lncRNAs. Bivariate logistic regression analysis showed that 19 GI-derived lncRNAs were prognostic factors. By further multivariate logistic regression analysis, AC005256.1 (estimated coefficient = -0.474), AC026336.3 (estimated coefficient = -0.030), AL161618.1 (estimated coefficient = -1.661), and BX322234.1 (estimated coefficient = 1.511) were used to construct a prognostic risk model. In the train set and test set, the risk model was shown to have both a high prognostic and a diagnostic value. CONCLUSION: We developed a novel GI-derived 4-lncRNA signature for the diagnosis and prognosis of patients with endometrial cancer. These findings offered a novel perspective in the clinical management of endometrial cancer.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Instabilidade Genômica , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Bases de Dados Genéticas , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...