We aimed to establish an immune-related gene (IRG) based signature that could provide guidance for clinical bladder cancer (BC) prognostic surveillance.Differentially expressed IRGs and transcription factors (TFs) between BCs and normal tissues were extracted from transcriptome data downloaded from the TCGA database. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to identify related pathways based on differently expressed IRGs. Then, univariate Cox regression analysis was performed to investigate IRGs with prognostic values and LASSO penalized Cox regression analysis was utilized to develop the prognostic index (PI) model.A total of 411 BC tissue samples and 19 normal bladder tissues in the TCGA database were enrolled in this study and 259 differentially expressed IRGs were identified. Networks between TFs and IRGs were also provided to seek the upstream regulators of differentially expressed IRGs. By means of univariate Cox regression analysis, 57 IRGs were analyzed with prognostic values and 10 IRGs were finally identified by LASSO penalized Cox regression analysis to construct the PI model. This model could significantly classified BC patients into high-risk group and low-risk group in terms of OS (P=9.923e-07) and its AUC reached 0.711. By means of univariate and multivariate COX regression analysis, this PI was proven to be a valuable independent prognostic factor (HR =1.119, 95% CI =1.066-1.175, P<0.001). CMap database analysis was also utilized to screen out 10 small molecules drugs with the potential for the treatment of BC.Our study successfully provided a novel PI based on IRGs with the potential to predict the prognosis of BC and screened out 10 small molecules drugs with the potential to treat BC. Besides, networks between TFs and IRGs were also displayed to seek its upstream regulators for future researches.
To investigate effects moxibustion exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Crohn's disease (CD). C57BL/6 wild type (WT) and A20IEC−KO mice (48 each) were randomly divided into normal control (NC), model control (MC), mesalazine (MESA) and herbs-partitioned moxibustion (HPM) groups (12 mice per group). An experimental model of CD was established using 2, 4, 6 trinitrobenzene sulfonic acid. MESA and HPM mice were treated with MESA and HPM (at Tianshu (ST25) and Qihai (CV6)), respectively. In HPM group, moxa cones (0.5 cm in diameter and 0.3 cm in height) made of refined mugwort floss were placed on herbal cakes (medicinal formula dispensing [radix] Aconiti praeparata, [cortex] Cinnamomi, etc.) at Tianshu (ST25) and Qihai (CV6) and ignited. The moxa cones were ignited, and two moxa cones were used for each treatment once daily for 10 days. In MESA group, mice were fed MESA, which was prepared at a proportion of 1:0.0026, twice daily for 10 days. Intestinal epithelial ultrastructure of WT HPM mice improved more than A20IEC−KO HPM mice compared to MC mice. WT HPM mice exhibited greater expression of A20 compared with MC mice (P < 0.01). TNF-α, NF-kB p65, MLCK, MLC, TRAF6 and RIP1 levels in A20IEC−KO and WT HPM mice were all decreased compared to MC mice (Pall < 0.01). NF-κB p65、MLCK and TRAF6 levels were increased in A20IEC−KO HPM mice as compared to WT HPM mice (Pall < 0.05). Intestinal epithelial levels of occludin, claudin-1, ZO-1 and F-actin increased in all HPM mice (Pall < 0.01–0.05), while occludin, claudin-1, and ZO-1 levels were lower in A20 IEC-KO HPM mice (P < 0.05, P < 0.01, P < 0.01). HPM downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway by upregulating expression of A20 in a mouse model of CD, thereby protecting intestinal epithelial tight junctions and repairing the damage CD causes to the intestinal epithelial barrier.
Objective
To summarize the experience of diagnosis and treatment of rare type of hepatic benign space occupying lesions.
Methods
The clinical data of 113 patients with rare type of hepatic benign space occupying lesions confirmed by surgery and pathology from Jan 2009 to Dec 2018 were retrospectively analyzed.
Results
There were 51 males and 62 females , age ranging from 12 to 83 years, with an average of 44.3 years. 91.2% of the 113 cases were single lesions and 8.8% were multiple lesions. Surgical methods included hepatectomy in 98 cases, ablation therapy in 12 cases and hepatectomy combined with ablation in 3 cases. There were 21 types of pathology in 113 patients. The top five types were focal nodular hyperplasia (30 cases), hepatocellular adenoma (16 cases), dysplasia nodules (14 cases), perivascular epithelioid cell tumors (12 cases), and mucinous cystic neoplasms (11 cases), accounting for 73.5% cases. All the patients were alive in the follow-up period ranging from 6 to 120 months.
Conclusion
Preoperative diagnosis of rare benign space-occupying lesions of the liver is very difficult. Preoperative MRI is helpful for diagnosis. Conservative treatment or follow-up observation can be considered for the type malignancy have never been reported. For the borderline types or those with difficulty in definite diagnosis, surgical removal is recommended.
Key words:
Liver neoplasms; Surgical procedures, operatives
Rationale: Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive inherited disease that causes severe systemic joint deformity and articular dysfunction in young patients. Patient concerns: Ilizarov technique treatment in PPD patients has never been reported before. Diagnoses: A 17-year-old male patient presented with a 10-year history of polyarthritis and 4-year history of progressive hip and knee pain and stiffness. Genetic testing for the WISP3 gene was done and showed compound heterozygous mutations: NM_198239.1 (WISP3):c.1064_1065dupGT (p.Gln356ValfsTer33) and NM_198239.1 (WISP3):c.643+2T > C. Interventions: Taking his young age into consideration, the Ilizarov external fixation technique was adopted for the treatment of the deformity in knees. Outcomes: One year after the operation, the improvement of joint deformity was satisfactory. Lessons: The Ilizarov technique is economical and less invasive, and most importantly, it can delay the possible arthroplasty. It gives young PPD patients with arthropathy an alternative treatment.
We conducted a case-control study to investigate the associations of functional single-nucleotide polymorphisms in the purinergic P2X7 receptor (P2X7R) gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with obesity and overweight in a population of Chinese postmenopausal women.Our study included 180 obese women, 179 overweight women, and 204 controls. All participants were genotyped at the P2X7R rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143 loci via allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism procedures. The relationships between P2X7R genetic polymorphisms and their associated haplotypes with obesity (body mass index [BMI] ≥30 kg/m] and overweight (25 kg/m ≤ BMI < 30 kg/m) were evaluated.Our results showed that P2X7R rs2230911G and rs1718119A were associated with an increased risk of obesity; in particular, both carriers of the rs2230911G allele and GG/(CG + GG) genotypes (G vs C, P < 0.001, odds ratio [OR] 2.87, 95% confidence interval [CI] 1.98-4.16; GG vs CC, P < 0.001, OR 8.76, 95% CI 3.29-23.35; CG + GG vs CC, P < 0.001, OR 2.54, 95% CI 1.63-3.95) and carriers of the rs17181191A allele and GA/(GA + AA) genotypes (A vs G, P < 0.001, OR 2.97, 95% CI 1.86-4.74; GA vs GG, P = 0.001, OR 2.72, 95% CI 1.55-4.79; GA + AA vs GG, P < 0.001, OR 3.05, 95% CI 1.79-5.19) were at a higher risk of obesity. No association with obesity or overweight was observed for the other three P2X7R polymorphisms (rs2393799, rs7958311, and rs3751143). Haplotype analysis indicated that P2X7R rs1718119A-rs2230911G-rs3751143C appeared to be a significant risk haplotype with obesity (P = 0.0005, OR 2.37, 95% CI 1.45-3.90).P2X7R functional genetic polymorphisms and their estimated haplotypes are associated with obesity in Chinese postmenopausal women.
Abstract Background: Aneuploid circulating endothelial cells (CECs) are an indicator in breast cancer (BC). Significant changes of aneuploid CECs occurred during neoadjuvant chemotherapy (NCT). The aim of this study was to explore the predictive and prognostic value of aneuploid CECs in locally advanced breast cancer (LABC) patients with different NCT responses. Methods: Breast cancer patients received an EC4-T4 NCT regimen. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for detection of CECs (CD45–/CD31+/DAPI+). Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of aneuploid CEC counts in distinguishing NCT-resistant patients from sensitive ones. All patients were observed for progression-free survival (PFS) and overall survival (OS). Results: The CEC counts at any time point did not show the ability to predict the efficacy of NCT. The difference of the CECs between post-chemotherapy level and baseline could be sufficient to distinguish chemotherapy-resistant cases from other cases in Hormone+Her-2-/+ (HR+) BC patients. Patients with reduction of CECs after all courses of NCT were associated with higher probability of PFS. Conclusion: Variation of aneuploid CECs during NCT may have some ability to predict chemotherapy response in patients with HR+ breast cancer. The decrease of aneuploid CECs number after all courses of NCT indicate better treatment outcomes in LABC patients.
Clinically, the renin-angiotensin-aldosterone system is activated intensely in patients with moderate to severe traumatic brain injury (TBI). Increased angiotensin II in circulatory blood after TBI can enter the brain through the disrupted blood-brain barrier. Angiotensin-converting enzyme 2 (ACE2) is an enzyme that metabolizes angiotensin II into angiotensin (1-7), which has been shown to have neuroprotective results. The expression and role of ACE2 in the brain after TBI remains elusive, however. We found that ACE2 protein abundance was downregulated around the contusional area in the brains of both humans and mice. Endogenous ACE2 was expressed in neurons, astrocytes, and microglia in the cortex of the mouse brain. Administration of recombinant human ACE2 intracerebroventricularly alleviated neurological defects after TBI in mice. Treatment of recombinant human ACE2 suppressed TBI-induced increase of angiotensin II and the decrease of angiotensin (1-7) in the brain, mitigated neural cell death, reduced the activation of NLRP3 and caspase3, decreased phosphorylation of mitogen-activated protein kinases, and nuclear factor kappa B, and reduced inflammatory cytokines tumor necrosis factor alpha and interleukin-1β. Administration of ACE2 enzyme activator diminazene aceturate intraperitoneally rescued downregulation of ACE2 enzymatic activity and protein abundance in the brain. Diminazene aceturate treatment once per day in the acute stage after TBI alleviated long-term cognitive defects and neuronal loss in mice. Collectively, these results indicated that restoration of ACE2 alleviated neurological deficits after TBI by mitigation of pyroptosis and apoptosis.
Objective To evaluate the effects and meaning of radiotherapy of esophagus cancer invading trachea or main bronchus.Methods 73 esophagus cancer invading trachea or main bronchus were analyzed retrrospetively.All cases were confirmed combining clinical symptom,the esophagus ray examination,gastroscopy,fiberoptic bronchoscopy,the CT or MRI 60Co or 6,15 MV X.Results 6 cases did not finish radiotherapy plan and all died in half year,patients receiving more than 40Gy,chest ache,voice hoarseness,emptysis and inspitation dyspnea symptom decreased rate were 87.2%,74.1%,99.3%,100% respectively,patients received 50~70Gy,the 0.5,l,2,3 year survival rates were 79.5%,68.5%,27.4% and 9.6%.Conclusion Esophagus cancer invading trachea or main bronchus is local advanced tumor,radiotheropy can improve the quality of patients,life and extend survival time obviously,receveing 60~70Gy is proper,survival rate make no difference of focus tumor size and the sites of trachea invaded.
Abstract Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characteristic of small airway inflammation, obstruction, and emphysema. It is well known that spirometry alone cannot differentiate each separate component. Computed tomography (CT) is widely used to determine the extent of emphysema and small airway involvement in COPD. Compared with the pulmonary function test, small airway CT phenotypes can accurately reflect disease severity in patients with COPD, which is conducive to improving the prognosis of this disease. CT measurement of central airway morphology has been applied in clinical, epidemiologic, and genetic investigations as an inference of the presence and severity of small airway disease. This review will focus on presenting the current knowledge and methodologies in chest CT that aid in identifying discrete COPD phenotypes.
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