Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury.Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin (20 mg/kg), and renal function and renal tissue pathology were tested;gene expression was analyzed and signaling pathways were en-riched in cisplatin-treated renal tubular epithelial cells using transcriptome; the contents of renal glycolysis and a-mino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) .Re-sults Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice.Pathological his-tology observed swelling and shedding of renal tubular epithelial cells.Transcriptome analysis revealed that 2632 genes were upregulated and 2799 genes were downregulated in cisplatin-treated HK-2 cells.GO and KEGG analy-sis showed that differential genes were enriched in energy metabolism.The GSEA analysis results showed that cispl-atin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells, further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells.Metabolomics showed that the contents of glycolytic intermediates and several a-mino acids were altered in the kidney of cisplatin-treated mice.Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.

Objective To observe the value of CT radiomics for differentiating spinal bone islands(BI)and osteoblastic metastases(OBM).Methods Data of 109 BI lesions in 98 patients and 282 OBM lesions in 158 patients(including 103 OBM in 48 lung cancer cases,86 OBM in 52 breast cancer cases and 93 OBM in 58 prostate cancer cases)from 3 medical institutions were retrospectively analyzed.Data obtained from institution 1 were used as the internal dataset and divided into internal training set and internal validation set at a ratio of 7∶3,from institution 2 and 3 were used as external dataset.All datasets were divided into female data subset(including OBM of female lung cancer and breast cancer)and male data subset(including OBM of male lung cancer and prostate cancer).Radiomics features were extracted and screened to construct 3 different support vector machine(SVM)models,including model1 for distinguishing BI and OBM,model2 for differentiating OBM of female lung cancer and breast cancer,and model3 for differentiating OBM of male lung cancer and prostate cancer.Diagnostic efficacy of model1,CT value alone and 3 physicians(A,B,C)for distinguishing BI and OBM were assessed,as well as differentiating efficacy for different OBM of model2 and model3.Receiver operating characteristic(ROC)curves were drawn,and area under the curves(AUC)were calculated and compared.The differential diagnostic efficacy of model2 and model3 were also assessed with ROC analysis and AUC.Results AUC of model1 for distinguishing spinal OBM from BI in internal training set,internal validation set and external dataset was 0.99,0.98 and 0.86,respectively.In internal training set,model1 had higher AUC for distinguishing BI and OBM than that of physician A(AUC=0.78),B(AUC=0.87)and C(AUC=0.93)as well as that of mean CT value(AUC=0.78,all P＜0.05).AUC in internal training set,internal validation set and external dataset of model2 for identifying female lung cancer and breast cancer OBM was 0.79,0.75 and 0.73,respectively,of model3 for discriminating male lung cancer from prostate cancer OBM was 0.77,0.74 and 0.77,respectively.Conclusion CT radiomics SVM model might reliablely distinguish OBM and BI.

Objective:To investigate the value of enhanced MRI in evaluating the tissue permeability of pancreatic ductal adenocarcinoma (PDAC) animal model.Methods:The experimental animals were 27 female C57BL/6 mice. The mice were divided into 3 groups with 9 mice in each group by random number method. Murine pancreatic adenocarcinoma (Panc02) and embryonic fibroblasts (NIH/3T3) were implanted subcutaneously at the ratio of 2∶1 and 1∶1 to establish PDAC models with different tissue permeability, which were low fibroblast group and high fibroblast group, respectively, and simple Panc02 implantation model was control group. The positive expression rate of α-smooth muscle actin (α-SMA), the positive expression rate of fibroblast activating protein (FAP), the coverage rate of collagen fibers, number of blood vessels and the long/short diameter of tissue vessels were quantitatively evaluated by tissue staining, and the tissue permeation efficiency was quantified by the average optical density (AOD) of tissue sections stained by Evans blue (EB). Enhanced MRI was performed on mice, and the enhancement degree and the enhancement rate of 20 min were obtained. One-way ANOVA was used to compare the overall differences of tumor histological indexes and MRI enhancement parameters in each group, and the correlation between the indexes was analyzed by Pearson correlation analysis. Multiple linear stepwise regression analysis was conducted with 20 min enhancement rate as dependent variable, while α-SMA positive expression rate, collagen fiber coverage rate and vascular long/short diameter as independent variables.Results:There were significant differences in AOD value, α-SMA positive expression rate, FAP positive expression rate, collagen fiber coverage rate, vascular long/short diameter, 20 min enhancement degree and 20 min enhancement rate among the three groups ( P<0.001), but there was no significant difference in the number of blood vessels ( P=0.650). The AOD value was negatively correlated with the positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels in PDAC model, respectively ( r=-0.888, P=0.001; r=-0.813, P=0.008; r=-0.915, P<0.001). The 20 min enhancement degree was positively correlated with AOD value ( r=0.954, P<0.001). The positive expression rate of α-SMA, collagen fiber coverage and vascular long/short diameter were negatively correlated with 20 min enhancement rate ( r=-0.901, P<0.001; r=-0.837, P=0.005; r=-0.880, P=0.002). The results of multiple linear stepwise regression analysis showed that the positive expression rate of α-SMA was an important influencing factor for the 20 min enhancement rate (R 2=0.813, P=0.001). Conclusions:The increase of fibroblast implantation ratio significantly decreased the permeation efficiency of tumor tissue. The positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels were negatively correlated with the permeation efficiency of tumor tissue. The 20 min enhancement degree was positively correlated with tissue permeation efficiency.

Objective:To investigate the feasibility of combination of en-bloc resection of bladder tumor (ERBT) with the NBI(narrow band imaging) flexible cystoscopy, immunotherapy and chemotherapy in bladder-preserving treatments(called as TMT) for patients with stage T 2 bladder carcinoma. Methods:We retrospectively reviewed and analyzed a series of 16 patients with pT 2N 0M 0 pathologically confirmed. All patients are male with a median age of 63yr(56, 73yr). The American Association of Anesthesiologists scored ≤Ⅱ in 12 cases and Ⅲ in 4 cases. There were 9 cases with smoking history, 5 cases with hypertension, 3 cases with diabetes, and 2 cases with heart disease. The results of preoperative tissue biopsy were all urothelial carcinoma. All patients were taken lithotomy position and performed ERBT with NBI imaging technique and thulium-laser energy platform under general anesthesia. The tumor was brown and the surrounding normal mucosa was cyan in color. The procedure was ensured with a minimal tumor margin of 1cm and minimal rection depth to the deep musculi, and with the acquirement for the en-bloc specimen of which the basal site was marked afterwards, the patients all took a full length of chemoimmunotherapy (four cycles of Tislelizumab combined with Gemcitabine and cisplatin regimens) followed by a secondary ERBT. The perioperative data from sequential operations including complications were comprehensively analyzed for evaluating the therapeutic outcome and safety. All patients received a follow-up to detect efficacy and safety of the treatment with the primary end point of pCR, downgrading rate and objective response rate. Results:All operations were successfully completed. There was no obturator reflex, severe bleeding or grade Ⅱ bladder perforation, only 4 patients got a grade Ⅰ bladder perforation. The postoperative 30-day complication occured in 2 cases(1 pt with hematuresis, 1 pt with bladder irritation). The pathologic complete response rate and tumor downstaging rate were 100%. One patient recurred during a median follow-up of 13.0 months (6, 36 months).Conclusions:The En Bloc Resection of Bladder Tumor with the narrow band imaging (NBI) flexible cystoscopy has several remarkable advantages, including a better intra-operative visual, a lower complication rate and tumor residual. The combination of ERBT with immunotherapy and chemotherapy lead to affirmative curative effect and the feasibility for clinical application is relatively high.

Objective:To compare the efficacy of ultrasound combined with endoscopy and ultrasound combined with X-ray guided percutaneous nephrolithotomy(PCNL) in the treatment of complex renal calculi.Methods:The clinical data of 119 patients with complex kidney stones treated by ultrasound combined with endoscopy or ultrasound combined with X-ray guided PCNL in the Second Affiliated Hospital of Anhui Medical University from March 2019 to February 2022 were analyzed retrospectively. According to different guidance methods, they were divided into ultrasound combined with endoscopic guidance group and ultrasound combined with X-ray guidance group.There was no significant difference in age [(53.9±14.2) years vs. (55.6±13.5) years], gender (male/female: 38/21 vs. 30/30), body mass index [(25.0±3.7) kg/m 2 vs. (24.8±3.8)kg/m 2], stone location (left/right: 34/25 vs. 31/29), maximum diameter of renal stones [(31.9±8.3)mm vs. (33.9±13.5)mm], kidney stones maximum cross-sectional area [(601.5±242.5)mm 2 vs. (632.6±278.9)mm 2], number of renal calices involved (3.5±0.9 vs. 3.6±1.3), S. T.O.N.E. scores (9.4±1.0 vs. 9.7±1.4), Guy's grade(Ⅲ/Ⅳ: 45/14 vs. 41/19), preoperative hemoglobin [(125.2±21.5)g/L vs. (125.6±18.4)g/L], serum creatinine[(89.1±33.8) μmol/L vs. (81.9±27.1) μmol/L], urinary tract infection (43/59 vs. 47/60)and positive urinary bacterial culture (12/59 vs.11/60) between the two groups(all P>0.05). The patients in the ultrasound combined with endoscopic guidance group were placed in the modified prone split-leg position. Flexible ureteroscope retrograde into the renal pelvis, combined with ultrasound to determine the best puncture calices. The channels were established and stones were removed under the guidance of ultrasound and endoscopy. In the ultrasound combined with X-ray guidance group, the F5 ureteral catheter was placed retrogradely into the operative side ureter under the lithotomy position. Then the patient changed to prone position and the target calices were punctured under the guidance of ultrasound and X-ray. Through anterograde or retrograde injection of contrast medium, the puncture position was determined to enter in the center of the calicean dome, and the channel establishment process and stone removal are monitored. The operative results and postoperative data were recorded. Results:The average operation time in the ultrasound combined with endoscopic guidance group was significantly shorter than that in the ultrasound combined with X-ray guidance group [(90.2 ± 34.5) min vs. (129.4 ± 43.0) min, P < 0.001]. There was no significant difference in the success rates of initial channel establishment [94.0% (63/67) vs. 87.7% (107/122), P = 0.167], the time of single channel establishment [(7.7 ± 1.9) min vs. (7.7 ± 1.4) min, P =0.765], serum creatinine on the first day after operation[ (89.3±33.6) μmol/L vs. (82.9±27.0) μmol/L, P=0.257] and postoperative hospital stay[(5.3±1.6) d vs.(5.4±1.7) d, P=0.883]. In contrast, patients in ultrasound combined with X-ray guidance group had higher stone free rate [93.3% (56/60) vs. 81.4% (48/59), P=0.049] and lower reoperation rate [3.3% (2/60) vs. 15.3% (9/59), P=0.025]. The mean hemoglobin decrease value of ultrasound combined with endoscopic guidance group was significantly lower than ultrasound combined with X-ray guidance group on the first day after operation [(8.7±6.3) g/L vs. (16.8±6.9) g/L, P<0.001]. The complication rate of ultrasound combined with endoscopic guidance group was significantly lower than that of ultrasound combined with X-ray guidance group [5.1% (3/59) vs. 16.7% (10/60), P = 0.043]. Conclusions:Ultrasound combined with endoscopic guidance PCNL does not need to change body position during operation and has fewer puncture channels, thus saving operation time and reducing complications. It is more suitable for patients with isolated kidney or easy bleeding. Ultrasound combined with X-ray guidance is conducive to the establishment of multi-channel, the stone clearance rate is high and the reoperation rate is low, which is suitable for patients with good health and more renal calices involved with stones.

Objective: To investigate the effects of sulforaphane (SFN) on proliferation , migration and invasion of human renal carcinoma cells and its mechanism. Methods: The cultured human renal carcinoma cells 786⁃O were divided into control group (0 μmol/L) and SFN group (5 , 10 , 20 μmol/L) . The activated proliferation of cells was detected by CCK⁃8 ; the effect of SFN on migration of 786⁃O cells was detected by scratch healing assay and Transwell cell migration assay; the effect of SFN on the invasion ability of 786⁃O cells was detected by Transwell cell invasion ability assay; Western blot and qRT⁃PCR were used to detect the effects of SFN on the expression of epithelial⁃mesenchymal transition (EMT) Ⅳrelated proteins and mRNA. The effect of SFN on the expression of NF⁃κB signaling pathway was detected by Western blot. Results: After SFN treatment for 24 , 48 and 72 h , the proliferation activity of 786⁃O cells decreased with the increase of SFN concentration ; compared with the control group , the cell migration and invasion ability of SFN⁃treated group were significantly reduced ; with the increase of SFN concentration , the mRNA and protein expression levels of E ⁃cadherin in 786⁃O cells increased , while the mRNA and protein expression levels of N ⁃cadherin and Vimentin decreased ; the levels of NF⁃κB signaling pathway related protein phosphorylated p65 and phosphorylated IκBα decreased with the increase of SFN concentration. Conclusion SFN may inhibit the proliferation , migration and invasion of human renal carcinoma cells by regulating the EMT process of renal carcinoma through inhibition of NF⁃κB signaling pathway.

Objective:To explore the clinical feasibility of extra-peritoneal laparoscopic radical cystectomy based on the concept of 3D membrane anatomy.Methods:The clinical data of 10 male patients with bladder cancer who underwent 3D extra-peritoneal laparoscopic radical cystectomy + ileal-orthotopic-neobladder surgery from October 2020 to June 2021 were retrospectively analyzed. The median age was 67 years. The ASA score was 1-2 in 8 cases and 3 in 2 cases. There were 4 cases of hypertension, 2 cases of diabetes, 1 case of heart disease, no case of abdominal surgery history. During the operation, the concept of 3D membrane anatomy was used to identify the important fascia in the pelvic cavity and to find the key layers and structures in the pelvic cavity.It was separated from the prevesical fascia to the laterovesical space, and confluenced with Retzius space and Bogros space. It was dissected in the layer surrounded by the prevesical fascia, the vesicohypogastric fascia, and the urogenital fascia to complete the process of cystectomy.Results:The operations of 10 patients were completed successfully and there was no conversion to open operation. The median operation time was 276(237-325) minutes, and the median blood loss was 160(50-280)ml. The postoperative bowel recovery median time was 1.8(1-3)days, and the patients were out of bed about 1.3(1-2) days. The median postoperative hospital stay was 9(5-12) days. The number of median lymph node dissection in all patients was 10(6-20). Positive lymph nodes was found in 3 cases. Positive margin was found in no case. Postoperative tumor pathological stages were T 2 stage in 7 cases, T 3 stage in 3 cases. During the follow-up, all patients had no obvious complications. Conclusions:It is feasible to apply the concept of 3D membrane anatomy to identify and locate the key fascia structures and levels in extra-peritoneal laparoscopic radical cystectomy. The operative complications were less and the postoperative recovery was faster. The anatomy is clear during the operation, which has good safety and reduces the difficulty of the operation.

Zinner syndrome is a congenital genitourinary embryo malformation, which is clinically rare, difficult to diagnose, and usually found in the sexually active stage. MRI is the preferred method for diagnosis. Conservative treatment was usually conducted for most asymptomatic patients. Symptomatic patients can be treated by laparoscopic or robotic surgery. For patients with infertility complicated with ejaculatory duct obstruction, transurethral resection of the ejaculatory duct is feasible, which contributes to improving sperm vitality and quantity and increasing semen volume. However, some patients still have azoospermia after surgery. The etiology is needed further studied. A case of infertility with Zinner syndrome and ectopic ureteral opening in seminal vesicle cyst is reported.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Objective:To establish a quick on-site emergency detection method for severe fever with thrombocytopenia syndrome virus (SFTSV), dengue virus (DENV), and hantaan virus (HTNV).Methods:This research was based on the traditional TaqMan fluorescent probe technology, using the domestic rapid one-step quantitative RT-PCR kit, combined with the Magnetic induction cycler (Mic) qPCR instrument. The detection limit, specificity and repeatability of this method were evaluated by simulated samples, other virus infected samples and normal human blood samples.Results:Compared with the traditional RT-PCR assay, the required time of this method was greatly shortened, and the detection can be completed within 35 minutes. The limit of quantitation for SFTSV, DENV and HTNV are less than 100copies/PCR. No nonspecific amplification was found in the simulated negative samples and other virus infected samples. All the simulated positive sample for verification could be detected, and coefficient of variation Ct value of each group was less than 4%. Conclusions:The rapid fluorescence quantitative RT-PCR assays have certain application prospects for on-site emergency detection, and provide important technical supports and new directions for the prevention and control of common hemorrhagic fever viruses.