Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

Child ; Humans ; Case-Control Studies ; East Asian People ; Genetic Predisposition to Disease/genetics* ; Methyltransferases/genetics* ; Polymorphism, Genetic ; Wilms Tumor/pathology*

【Objective】 To investigate the efficacy of the adjustable "paper clip" techniques in the suture of dorsal vein complex (DVC) and retention of urethral function in robot-assisted laparoscopic radical prostatectomy (RALRP). 【Methods】 A total of 30 cases of prostate cancer treated with RALRP were enrolled, all of which used the adjustable "paper clip" techniques. During operation, the DVC was sewed with barbed suture, and then a reverse suture was made through two sides of the prostatic ligaments. A Hem-o-lock was used to fasten the suture, which would be flexible to control the degree of tightness for the ligature. Perioperative and follow-up data of urinary continence and symptoms were collected and analyzed. 【Results】 All operations were successful. The estimated blood loss was (123.3±80.7) mL, 53.6% patients recovered continence in 1 month, and the continence rate increased to 92.9% and 96.3% at month 3 and 6. 92.9 of patients had no risk of incontinence 3 months after surgery. 【Conclusion】 The adjustable "paper clip" techniques have advantages in reducing blood loss, maintaining clear surgical field, preserving urethral function, and improving urinary continence.

Objective:To investigate the expression of vitamin D receptor(VDR)in biliary epithelial cells of children with biliary atresia(BA)and explore the correlation between VDR epression levels and clinical pathological prognosis.Methods:A total of 48 BA patients who underwent Kasai surgery in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi′an Jiaotong University from January 2017 to December 2020 with confirmed pathological results were selected as the study subjects.Immunohistochemistry was used to determine the expression of VDR in biliary epithelial cells, and Masson staining was used to determine the degree of liver tissue fibrosis.Based on the VDR expression levels, the 48 BA patients were divided into the significantly low VDR expression group(30 cases)and the normal/high expression group(18 cases).Laboratory testing results within 1 week before Kasai surgery and liver shear wave elastography(SWE)data were collected for all patients.Follow-up was conducted for a period of 0 to 60 months after Kasai surgery or liver transplantation, meanwhile, the occurrence of refractory cholangitis and auto-liver survival time were collected.Results:There was a negative correlation between the degree of liver fibrosis and SWE value in children with BA( r=-0.805, P<0.01).In comparison between the two groups, the significantly low VDR expression group had higher SWE values[(20.57±1.28)kPa vs.(18.02±1.41)kPa, P<0.05], higher liver injury biochemical indicators[ALT(215.8±24.7)U/L vs.(182.6±21.2)U/L, P=0.021; AST(165.4±22.3)U/L vs.(139.6±21.4)U/L, P=0.014], a higher frequency of post-Kasai surgery refractory cholangitis(60.00% vs.22.22%, P=0.037), and a shorter median autologous liver survival time(27.00 months vs.36.00 months, P=0.032)than those in the normal/high expression group. Conclusion:The significant decrease in VDR expression in biliary epithelial cells may serve as an indicator of poor prognosis in BA.

Objective:To explore the possible role and clinical significance of vitamin D receptor (VDR) in intrahepatic bile duct epithelial cells (IBDECs) in biliary atresia (BA).Methods:A retrospective analysis was performed on expression level of VDR in IBDECs of 38 BA children who underwent Kasai surgery in the Second Affiliated Hospital of Xi′an Jiaotong University and the Children′s Hospital of Xi′an Jiaotong University from January 2015 to December 2019.Expression level of VDR in IBDECs of 38 children with BA was detected by immunohistochemical staining, and that in children with choledochal cysts was detected as negative control.Masson staining was performed to examine the degree of liver fibrosis.The correlation between the expression level of VDR in IBDECs of children with BA, and the degree of liver fibrosis during operation, the incidence of refractory cholangitis after Kasai portoenterostomy and the survival time of autologous liver was analyzed.Human intrahepatic bile duct epithelial cells (HiBECs) were induced with dsRNA virus infection by polyinosinic acid-polycytidylic acid [Poly(I∶C)] in vitro, followed by detection of cell activity, apoptosis and VDR level.The differences between 2 independent groups were analyzed using Student t test.The relationship between the expression of VDR and clinicopathologic characteristics was conducted with χ2 test or Fisher′ s test.The Kaplan- Meier survival curve was used to analyze the differences in the survival time of autologous liver after Kasai in BA children with different VDR expression levels. Results:A total of 38 children with BA were included in this study.Among them, 23 cases showed no significant decrease of VDR protein level in IBDECs, and 15 cases showed a significant decrease in IBDECs.Compared with BA children without a significant decrease in VDR level in IBDECs, much severer liver fibrosis ( P<0.001) and significantly higher incidence of refractory cholangitis after Kasai procedure ( P=0.017) were detected in those with a significant decrease in VDR level.Compared with the control group, BA children with significantly lower VDR expression levels in HiBECs had a shorter autologous liver survival time ( P=0.030). Poly (I∶C) increased the apoptotic rate of HiBECs ( P<0.000 1) and decreased cell activity of HiBECs ( P<0.05), which significantly stimulated the secretion of inflammatory factors (interferon, tumor necrosis factor-α, interleukin-6) in the culture medium of HiBECs ( P<0.001). Poly (I∶C) significantly decreased the expression level of VDR protein in HiBECs ( P<0.001). Conclusions:Poly (I∶C) causes HiBECs damage and decreases VDR expression level in HiBECs of BA children, and the significantly decreased VDR expression level in IBDECs may be a marker of poor prognosis of BA.

Objective:To investigate the feasibility and safety of suprapubic bladder puncture and gland fixation in transurethral enucleation of the prostate.Methods:The clinical data of 15 patients with benign prostatic hyperplasia admitted to the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2020 were retrospectively analyzed. The age was (70.27±5.35) years old, preoperative serum prostate-specific antigen (PSA) level was (3.03±1.37) ng/ml, preoperative total prostate weight was 80.3(70.49, 96.78)g, preoperative postvoid residual urine volume(PVR)was 80 (55, 108)ml, and the maximum urine flow rate (Q max) was (6.13±2.25) ml/s. The international prostate symptom score(IPSS) was 25(22, 27), quality of life (QOL)score was 5(5, 6), international erectile function index-5 (IIEF-5) score was (15.38±5.10). All 15 patients underwent conventional transurethral plasma enucleation of prostate by using the three-lobe method, and the enucleated gland was pushed into the bladder completely. Then a laparoscopic pneumoperitoneum needle was used to perform suprappubic cystipuncture, and ureteral grasping forceps were inserted through the outer sheath. The forceps were used to fix the enencied gland. A rapid harvesting electric resection was performed in the broad space of the bladder, and the Ellick was rinsed to remove the tissue fragments. Surgical indicators and complications were recorded. The improvement of subjective score (IPSS, QOL, IIEF-5) and objective index (Q max, PVR) was compared between preoperative and postoperative. Results:All the 15 operations were completed successfully and there were no complications such as blood transfusion, capsule perforation, transurethral resection syndrome, bladder injury, bladder puncture site laceration and bleeding. The weight of resected prostate tissue was 44(40, 60)g, with blood loss (79.20±18.93)ml.The time of enucleation operation was (54.13±10.88)min, with harvest cutting time (14.67±2.50)min, evisceration efficiency (0.89±0.08)g/min, harvesting efficiency (3.26±0.36)g/min, bladder irrigation time (2.47±0.52) d. The time of indwelling catheter was (3.73±0.80)d.The postoperative hospital stay was (4.40±0.91) d. Temporary urinary incontinence occurred in 1 case after operation. All patients were followed up for 6 months after operation. The IPSS score was 3(2, 3), QOL score was 0(0, 1), IIEF-5 score was (20.12±2.30), Q maxwas (21.80±2.14) ml/s and PVR was 10(5, 15)ml, which were all significantly different compared with those before surgery ( P<0.05). The symptoms of the patients were significantly improved. Conclusions:Transurethral plasma enucleation of prostate combined with suprapubic bladder puncture and fixed gland is effective in the treatment of benign prostatic hyperplasia. The subjective symptoms and objective examination of patients have been significantly improved, and no adverse operation-related complications have occurred. It is a suitable method for enucleation of prostate in units which are not equipped with transurethral tissue planer.

The gut brain axis consists of bidirectional' routes of communication between the enteric nervous system and the central nervous system. Intestinal dysfunction can increase the risk of neurodegenerative disease, neuropsychiatric disease and other central system diseases. Improving intestinal function could alleviate symptoms of central system diseases, while the mechanism of that is still unclear. This article reviews the mechanism of intestinal regulation on brain in the gut brain axis.

Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5％ (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8％(8/54), 38.7％(24/62) and 58.3％ (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95％CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95％CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95％CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95％ CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.

Objective To investigate the the operative time of two stage soft ureteroscope lithotripsy for hemorrhagic embolism after percutaneous nephrolithotomy(PCNL).Methods The clinical data of 1 patient with massive hemorrhage after PCNL who treated with superselective renal artery embolization and ureteral soft lens were analyzed.Results The patient with postoperative bleeding after PCNL was treated with superselective renal artery branch embolization,after 30d embolization,the holmium laser lithotripsy under the soft ureteroscope for ureteral calculi was performed,and the renal pelvis mucosa smooth,no bleeding and scar formation were intraoperative visible.After operation,the stone was removed basically,and the double J tube was removed 2 weeks after operation.The patient had no special discomfort and the renal function was normal.Conclusion Postoperative 14-30d is a relatively safe time to perform flexible ureteroscopic lithotripsy for super selective renal artery embolization in the treatment of patient with massive hemorrhage after PCNL.

Objective To understand the early experiences of acute ischemic stroke (AIS) patients after intravenous thrombolysis. Methods By purposive sampling method, and according to principle of sample saturation, semi-structure interview was conducted to inpatients who had undergone acute ischemic stroke and were treated with intravenous thrombolysis in Neurology Department in a comprehensive class Ⅲ grade A hospital in Shenzhen from March to September 2016. Colaizzi method was used for the analysis of interview content. Results Early experiences of acute ischemic stroke patients after intravenous thrombolysis can be concluded as four subjects: perceived body difference, heavy psychological burden, adaptation to new roles, and expectation of support from medical staff and family members. Conclusions For AIS patients, different experiences and needs appeared from the attack to the recovery period after thrombolysis, according to which, individualized nursing measures should be adopted by doctors and nurses.