ABSTRACT
Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.
Subject(s)
Humans , Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/prevention & control , Treatment Outcome , ChinaABSTRACT
Colon cancer is a malignant tumor that harms human health. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with colon cancer remains poor. Ubiquilin-2 (UBQLN2) is a member of the ubiquitin family, actively implicated in the degradation of misfolded and redundant proteins through the ubiquitin-proteasome system and macroautophagy. However, the role and mechanism of UBQLN2 in colon cancer are not clear. This study was designed to explore the role of UBQLN2 in colon cancer and whether the Wnt pathway is involved. IHC and Western blotting analysis showed lower UBQLN2 expression in colon cancer tissues and cells (P<0. 05), and exhibited a negative correlation of UBQLN2 expression with clinical stage and lymph node metastasis (P< 0. 05). CCK-8 assay and flow cytometry demonstrated that UBQLN2 expression could inhibit colon cancer cell proliferation and promote cell apoptosis (P<0. 05). Western blotting analysis reveals that suppression of UBQLN2 enhances Bcl-2 expression but inhibits Bax and Wnt signaling. Taken together, these results showed that UBQLN2 inhibits proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt signaling pathway.
ABSTRACT
Sine oculis homeobox homolog 1 (SIX1) is involved in the regulation of many kinds of tumors and plays an important role in the occurrence and development of breast cancer, but the exact mechanism remains to be explored. In this study, we analyzed the expression of SIX1 in breast cancer, and investigated the role of SIX1 in the proliferation and invasion of breast cancer cells. TCGA database and GEPIA2 showed that the expression of SIX1 in breast cancer was significantly higher than that in normal tissues, which was confirmed in different molecular subtypes of breast cancer, including Basal-like, HER2, Luminal A and Luminal B (P < 0. 05). Besides, the analysis of HPA database also showed that the expression of SIX1 was significantly upregulated in breast cancer, and the difference was statistically significant (P < 0. 001). After interfering with the expression of SIX1 in the breast cancer cell line MDA-MB-231 and overexpressing SIX1 in MCF-7, the growth curve and EdU results showed that the proliferation of breast cancer cells was inhibited after knocking down SIX1, while overexpression of SIX1 could promote the proliferation ability (the growth curve assays: P < 0. 05; EdU assays: P < 0. 001). Besides, Transwell assays showed that SIX1 could enhance the invasion ability of breast cancer cells (P < 0. 001). In TCGA database we defined the high and low expression populations according to the upper and lower quartiles of SIX1 gene expression, and differentially expressed genes were found to be associated with metabolism and stem cell regulatory pathways. For further confirmation, high-throughput RNA deep sequencing (RNA-seq) was conducted using SIX1-knockdown cells, and analysis also showed that SIX1 was closely related to metabolism, stem cell regulation and EMT pathways. We selected several representative genes, MYC, SNAI2 and EGFR, to examine their associations with SIX1 expression and prognosis in patients with clinical breast cancer using published GEO datasets and KM-plotter, we found that SIX1 was positively correlated with the expression of MYC, SNAI2 and EGFR, and the high expression of SIX1, MYC, SNAI2 and EGFR is not conducive to the survival of breast cancer patients. GCBI, GeneMANIA and String online tools were conducted to predict the associated genes, lncRNA and miRNA of SIX1. Collectively, our study initially revealed the role of SIX1 in breast cancer and its regulatory mechanism, providing new insights for further studies.
ABSTRACT
BACKGROUND AND OBJECTIVE@#Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.@*METHODS@#Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively.@*RESULTS@#A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition.@*CONCLUSIONS@#In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Subject(s)
Animals , Male , Mice , Dexamethasone/therapeutic use , Disease Models, Animal , Kupffer Cells/physiology , Liver Failure, Acute/pathology , Mice, Inbred C57BL , Nuclear Receptor Subfamily 4, Group A, Member 1/physiology , Receptors, Glucocorticoid/physiologyABSTRACT
BACKGROUND@#The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups.@*METHODS@#Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted.@*RESULTS@#Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4@*CONCLUSIONS@#The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4
Subject(s)
Humans , Age Factors , Blood Cell Count , CD4 Lymphocyte Count , COVID-19/pathology , Cough , Dizziness , Headache , Patient Discharge , Recurrence , Risk FactorsABSTRACT
With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.
Subject(s)
Humans , China , Dendritic Cells/immunology , Immunity, Cellular , Immunotherapy/methods , Killer Cells, Natural/immunology , Neoplasms/therapy , Patient Selection/ethics , T-Lymphocytes/immunologyABSTRACT
<p><b>OBJECTIVE</b>To study the clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia (BPD).</p><p><b>METHODS</b>A prospective study was performed on the clinical data of 59 premature infants (gestational age <32 weeks) with BPD. Among the 59 premature infants, 37 cases had mild BPD and the other 22 cases had moderate to severe BPD. The clinical and imaging data were compared between these premature infants with different degrees of BPD.</p><p><b>RESULTS</b>The durations of mechanical ventilation, oxygen therapy, antibiotic therapy, parenteral nutrition, and hospitalization in the moderate to severe group were significantly longer than those in the mild group (P<0.05). The incidence of nosocomial infection and number of times of red blood cell transfusion in the moderate to severe group were significantly higher than that in the mild group. The rates of X-ray changes, including grade I respiratory distress syndrome (1 day after birth) and hypolucency of lungs (4-10 days and ≥ 28 days after birth) were significantly higher in the mild group than in the moderate to severe group. The rates of X-ray changes in classical BPD stage III (4-10 days after birth) and IV (≥ 28 days after birth) were significantly higher in the moderate to severe group than in the mild group.</p><p><b>CONCLUSIONS</b>The durations of mechanical ventilation, oxygen therapy, and antibiotic therapy and the incidence of nosocomial infection are correlated with the severity of BPD. The premature infants with severer BPD need a longer duration of parenteral nutrition and more times of red blood cell transfusion and have more typical imaging changes of BPD. Imaging examination has a predictive value for the severity of BPD.</p>
Subject(s)
Female , Humans , Infant, Newborn , Male , Bronchopulmonary Dysplasia , Diagnostic Imaging , Infant, Premature , Radiography, Thoracic , Tomography, X-Ray ComputedABSTRACT
The cross reactivity of mimotopes of hepatitis C virus (HCV) hypervariable region 1 (HVR1) was investigated to obtain epitopes that have high cross reactivity. Five expression vectors encoding B cell mimotopes fused with Trx were constructed, and the mimotope proteins were purified. The cross reactivity of mimotope proteins with HCV positive sera was determined by ELISA. HCV pseudotype particles (HCVpp) were generated and applied to evaluate neutralization effects of the sera of BALB/c mice immuned with the mimotope proteins on infection of Huh7. 5 cells. Our data showed that the mimotope proteins (P1, P2, P5, P6, P8) could react to the HCV positive sera. The HCVpp infection inhibition of the sera of BALB/c mice immuned with P6 or P8 was detectable. These results suggest that the mimotopes may be valuable in the studies of anti-HCV infection and development of HCV vaccines.
Subject(s)
Animals , Humans , Mice , Amino Acid Sequence , Complementarity Determining Regions , Allergy and Immunology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Epitopes , Hepacivirus , Allergy and Immunology , Mice, Inbred BALB C , Molecular Sequence DataABSTRACT
<p><b>OBJECTIVE</b>To explore the role of eotaxin in the pathogenesis of bronchial asthma and the clinical value in the diagnosis of asthma.</p><p><b>METHODS</b>Serum eotaxin were measured by ELISA in 38 patients with asthma, 28 patients with non-asthma allergy, and 30 healthy controls.</p><p><b>RESULTS</b>The levels of serum eotaxin in the asthma group were higher than those in the non-asthma allergic and control group (P<0.01). Furthermore, eotaxin levels in patients with acute asthma were significantly higher than those in patients with stable asthma (P<0.001). It was also found that the eotaxin levels of the acute asthma group were positively correlated to the amounts of eosinophils in peripheral blood (r=0.4196, P<0.001), and inversely correlated to the forced expiratory volume in one second (FEV1) (r=-0.3746, P<0.001).</p><p><b>CONCLUSION</b>It suggests that eotaxin may play a crucial pathogenic role in the asthmatic process possibly by activating the allergic inflammatory cells and controlling the recruitment of eosinophils from blood to bronchial epithelium of the airway. The concentration of eotaxin is significantly associated with the attack of acute asthma and its severity. Eotaxin may be a potential therapeutic target in patients with asthma.</p>