Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer.

BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.

[Poking reduction cannulated screw for the treatment of Sandersâ ¡ calcaneal fracture].

OBJECTIVE: To evaluate clinical effect of poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture. METHODS: From October 2014 to December 2017, 28 patients with Sanders Ⅱ calcaneal fracture were treated with poking reduction cannulated screw guided by Pingle orthopedic muscle-bone interoperability balance theory, including 20 males and 8 females, aged from 24 to 55 years old with an average of (37.2±3.9) years old. Calcaneal width, Bhler angle, and Gissane angle were measured before and after operation, and Maryland Score before and 6 months after operation were compared. RESULTS: All patients were followed up from 12 to 16 months with an average of (13.7±1.3) months. All fractures healed normally, and healing time ranged from 9 to 12 weeks with an average of (10.2±1.3) weeks. No postoperative wound infection, cortical necrosis, or osteomyelitis occurred. The width of the calcaneus decreased from (34.15±2.58) mm before surgery to (30.49±2.37) mm after surgery, Bhler angle increased from (14.16±3.27)° before operation to (31.95±3.07)°after operation, Gissane angle decreased from (128.45±9.04)° before operation to (120.83±8.15)° after operation. Maryland Score was 15.68±4.73 before operation, and was improved to 88.32±2.65 at 6 months after operation;19 patients got excellent result, 6 good, 2 fair and 1 poor. CONCLUSION: Poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture has certain clinical effects, high acceptation of patient, and without special demand for soft tissue around fracture. But it should avoid choosing severe comminuted Sanders Ⅲand Ⅳcalcaneal fracture.

Single-nucleotide polymorphisms of APE1 associated with risk and prognosis of vitiligo in a Han Chinese population.

BACKGROUND: The single-nucleotide polymorphisms (SNPs) of apurinic/apyrimidinicendonuclease 1 (APE1), which has been implicated in cancers and the DNA base excision repair (BER) process, have not been thoroughly investigated in association with the risks of oxidative stress-related vitiligo. OBJECTIVES: The aim of this study is to investigate associations between APE1 single-nucleotide polymorphisms 141T >G and 1349T >G and risk and prognosis of vitiligo. MATERIAL AND METHODS: From June 2013 to June 2015, a total of 460 vitiligo patients were randomly recruited as a case group; 200 of these patients received narrow bound ultraviolet B (NB-UVB) treatment. Meanwhile, 460 healthy controls were included as a control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to explore the distribution frequencies of genotypes. RESULTS: Significant differences were detected between the case group and the control group in the frequencies of the 141T >G and 1349T >G genotypes. At 141T >G, compared with patients carrying the TG + GG genotype, male patients carrying the TT genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Binary logistic regression analysis demonstrated that the TT genotype at 141T >G and the non-TT genotype at 1349T >G were independent risk factors for vitiligo development. At 1349T >G, compared with patients carrying the TT genotype, male patients carrying the TG + GG genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Moreover, patients carrying 141TG + GG or 1349 TT genotypes had better photochromic effects, lower cumulative radiation doses, shorter treatment times, and earlier first photochromic times.

Primary cutaneous zygomycosis due to Absidia corymbifera in a patient with cutaneous T cell lymphoma.

A slowly enlarging arm ulcer appeared in a 61-year-old man with cutaneous T cell lymphoma. Skin biopsy revealed aseptate hyphae and nodular small/medium-sized pleomorphic CD4(+) T cell infiltration. Cultures yielded Absidia corymbifera which was identified by phenotypic and molecular methods. Since a thorough examination did not detect organ involvement, the patient was diagnosed as having primary cutaneous zygomycosis. This is the first case report of cutaneous zygomycosis caused by A. corymbifera in a patient with primary cutaneous CD4(+) small/medium-sized pleomorphic T-cell lymphoma. Other cases of primary cutaneous zygomycosis caused by A. corymbifera are also reviewed.