Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.

In case of ischemic stroke(IS),thrombus in the vascular system can cause ischemia and hypoxia in brain tissue,produce inflammatory cytokines and cause brain tissue damage,while reactive oxygen species during ischemia-reperfusion cause stress injury.Conventional drug administra-tion is limited by the selective permeability of the blood-brain barrier and the low bioavailability of the drug itself,and its therapeutic effect against IS is unsatisfactory.Nanomedicine is expected to bring hope in that it has a unique mechanism of action and can cross the blood-brain barrier to reach the periphery of the infarct,release drugs or therapeutic genes,and exert a therapeutic effect.Nanomedi-cine inhibits platelet aggregation,enhances the efficacy of thrombolytic drugs,dissolves thrombus,increases blood supply to ischemic areas,eliminates reactive oxygen species and weakens injury response by fighting inflammatory cytokines.Loaded therapeutic genes regulate the differentiation pro-cess of neural stem cells,increase the number of neurons,induce the occurrence of blood vessels,and enhance the repair function of brain tissue.Nanomedicines can not only improve pharmacokinetics and pharmacodynamics to achieve more effective drug treatment,but also use nanoimaging technology to achieve real-time monitoring and condition assessment of therapy.

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

Sepsis is a life-threatening multiple organ dysfunction disease with high mortality and has become leading causes of death affecting intensive care unit (ICU) patients. Both long non-coding RNA (lncRNA) and microRNA (miRNA) are involved in the pathophysiological process of sepsis and can regulate the inflammatory response, both of which could be used as important diagnostic indicators and therapeutic targets of sepsis. The interaction among lncRNA, miRNA and messenger RNA (mRNA) plays an important role in sepsis and multiple organ dysfunction. This paper reviewed the regulatory relationship of lncRNA, miRNA and mRNA, as well as the regulatory role of lncRNA-miRNA-mRNA axis in inflammatory immune response and multiple organ dysfunction syndrome in sepsis, to provide new targets and strategies for the treatment of sepsis and organ dysfunction.

Objective: To detect the expression of miR-373 in osteosarcoma cells and explore its effects on cell proliferation, invasion, and migration. Methods: Human osteosarcoma cell line SJSA-1 and human osteoblast hFOB 1.19 cultured in vitro. Human osteosarcoma cell line SJSA-1 were randomly divided into four groups: blank control group (CK group), negative control group (NC group), miR-373 over-expressed plasmid group (miR-373 mimic group) and miR-373 inhibited plasmid group (miR-373 inhibitor group). Cells were transfected with FuGENE^® HD transfection reagent. After 48 hours of transfection, the relative expression of miR-373 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell proliferation by cell counting kit-8 (CCK-8) and cell invasion and migration by Transwell. Results: The relative expression of miR-373 in SJSA-1 cells was significantly higher than that in hFOB-1.19 cells (P<0.05); compared with CK group and NC group, the relative expression of miR-373 in the miR-373 mimic group increased significantly (P<0.05), and the relative expression of miR-373 in the miR-373 inhibitor group was significantly lower than that in the control group (P<0.05); optical density (OD) value of miR-373 mimic group at 24 h, 36 h, and 48 h were significantly higher than that of CK group and NC group (P<0.05), and OD value of miR-373 inhibitor group at 24 h, 36 h, and 48 h were significantly lower than that of CK group and NC group (P<0.05); the number of cell migration in the miR-373 mimic group was significantly higher than that in the CK group and NC group (P<0.05), and the number of cell migration in the miR-373 inhibitor group was significantly lower than that in CK group and NC group (P<0.05); the number of cell migration in the miR-373 mimic group was significantly higher than that in the CK group and NC group (P<0.05), and the number of cell migration in the miR-373 inhibitor group was significantly lower than that in CK group and NC group (P<0.05). Conclusions The expression of miR-373 is up-regulated in osteosarcoma. Overexpression of miR-373 can promote the proliferation, invasion, and migration of osteosarcoma cells, while the low expression of miR-373 can inhibit the proliferation, invasion, and migration of osteosarcoma cells, which may be an important target for the diagnosis and treatment of osteosarcoma.

Objective:To discuss the diagnosis and treatment of ectopic ureter company with the bladder neck and urethral maldevelopment in children.Methods:The clinical data of the 6 patients admitted to Children’s Hospital affiliated to Chongqing Medical University from September 1993 to April 2019 diagnosed as ectopic ureter company with the bladder neck and urethral maldevelopment were retrospectively reviewed. The 6 children were girls and the median age was 7 years old , ranged from 2 to 15 years old. All children had ectopic ureter, including 3 in left-sided, 1 in right-sided, and 2 in bilateral-sided. Five children presented the intermittent dribbling incontinence and one child presented the continuously incontinence without normal voiding. Through ultrasound, IVP, MRI, cystoscopy and retrograde urography, seven ureters were found ectopic position, including bladder neck in 4 cases, two ureters inserted in the vagina in 2 cases. There were two cases with duplex kidney and 4 cases with renal dysplasia. Preoperative cystoscopy revealed wide and short urethra in 1 case, wide bladder neck combined with wide and short urethra in 4 cases. The surgery type included nephrectomy in cases 1-3, bilateral ureter reimplantation in case 4 who had the bilateral ectopic ureter , bilateral ureter reimplantation and bladder neck reconstruction at the same time in case 5. Nephrectomy associated with bladder neck and urethral reconstruction in case 6.Results:Five patients were followed-up and one patient was lost to follow-up after the first operation. Mean follow-up was 41.2 months (ranging 2 to 84 months). Four patients with bladder neck and maldevelopment that were not solved intraoperatively got reoperations due to incontinence without remission. Case 1, who underwent urethral reconstruction and extension, and urinary incontinence was partially relieved. Case 2 was found to have wide bladder neck deformity, and then retrospectively got bladder neck reconstruction and urethrovaginal fistula repair in 3 years and 5 years later. The urinary incontinence was completely relieved. The ureteral stump of case 3 was resected 2 years after operation due to recurrent urinary tract infection, and then got twice bladder neck and urethral reconstruction in 3 years and 6 years later of nephrectomy. His incontinence was partially relieved. The case 4 got bladder neck and urethral reconstruction in one year after bilateral ureter reimplantation, and incontinence was partially relieved too. Among the two patients underwent combined surgery, the case 5, who got bilateral ureteral bladder replantation combined with bladder neck reconstruction, were lost to follow-up after surgery. The case 6 got dysplasia nephrectomy combined with bladder neck reconstruction and urethroplasty were completely relieved of urinary incontinence.Conclusions:Bladder neck and urethra maldevelopment is one of the main causes of urinary incontinence after surgery in children with ectopic ureter. The diagnosis mainly relies on cystoscopy. The treatment mainly relies on surgery. Bladder neck and urethral reconstruction is expected to be available. If the operative conditions permit, synchronous surgical treatment of ectopic ureter and bladder neck and urethral maldevelopment will get a better prognosis than staging surgery.

In this article,the content of radiation physics in the ICRU report No.89 were interpreted in details,aiming to provide reference in the radiation physics for radiologists performing brachytherapy for cervical cancer patients.

This paper made a detailed interpretation about the radiobiology-related contents in the ICRU report No.89,aiming to provide reference to resolve the problems related to radiobiology for the colleagues occupied in the brachytherapy for cervical cancer.

Radiotherapy is an important part of the postoperative adjuvant therapy of cervical cancer. Along with the persistent development of radiotherapy techniques, the application of brachytherapy has been more and more used as a boost to external beam radiotherapy. In this artical, the indications of postoperative radiotherapy and the application of brachytherapy were reviewed.

Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models.Methods The nude mouse models with MCF-7 and HeLa xenografts were established.The degree of hypoxia and EGFR expression were observed by confocal microscopy.The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay.Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia.Furthermore,the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR.Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression.Under hypoxic conditions,EGFR exoression is negatively correlated with cell apoptosis.