Comparison of the One-Step Prone Split-Leg Position to the Traditional Prone Position for Percutaneous Nephrolithotomy: A Single-Center Retrospective Study.

PURPOSE: To evaluate the one-step prone split-leg position compared to the traditional prone position for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: This study retrospectively analyzed the clinical data for 102 patients with upper urinary tract calculi who underwent PCNL at our hospital from April 2019 to December 2022. All PCNL procedures were performed by the same senior urologist. According to different surgical positions, the patients were divided into a one-step prone split-leg position group (observation group, n = 39) and a traditional bladder lithotomy position followed by prone position group (control group, n = 63). Then, the two groups were compared regarding the time of catheter insertion and channel establishment, channel size, time required for double-J stent placement, total operative time, postoperative hospital stay, stone removal rate, secondary operation rate and postoperative complications. RESULTS: There was no significant difference in the preoperative baseline characteristics of the patients between the two groups (all P > .05). Patients in the observation group had shorter total operative times, higher stone removal rates (76.9% [30/39] vs. 57.1% [36/63], P = .042), and lower secondary operation rates (10.3% [4/39] vs. 28.6% [18/63], P = .029) than those in the control group. There were no significant differences in the time of working channel establishment, channel size, postoperative hospital stay, or postoperative complications between the two groups (all P > .05). CONCLUSION: The one-step prone split-leg position is a safe and reliable surgical posture for treating upper urinary calculi in PCNL patients. It can not only shorten the overall operation time of PCNL but also improve the stone removal rate of the operation, thus reducing the secondary operation rate of multiple renal stones.

M6A-mediated-upregulation of lncRNA BLACAT3 promotes bladder cancer angiogenesis and hematogenous metastasis through YBX3 nuclear shuttling and enhancing NCF2 transcription.

Lymphatic metastasis is recognized as the leading manner of metastasis in bladder cancer (BLCa), but hematogenous metastasis accounts for a majority of cancer-associated deaths. The past two decades have witnessed tremendous attention in long non-coding RNAs (lncRNAs), which are a new hope for the development of targeted drug therapy for metastatic cancers; however, the underlying mechanism of lncRNAs involved in BLCa hematogenous metastasis remains to be elucidated. Here, we identified BLCa-associated transcript 3 (BLACAT3), a lncRNA, which was aberrantly upregulated in BLCa and corelated with poor prognosis of patients with muscle-invasive bladder cancer. Methodologically, m6A epitranscriptomic microarray, RNA sequencing and mass spectrometry (MS) were used to screen the key molecules of the regulatory axis. Functional assays, animal models and clinical samples were used to explore the roles of BLACAT3 in BLCa in vitro and in vivo. Mechanistically, m6A modification contributes to BLACAT3 upregulation by stabilizing RNA structure. BLACAT3 recruits YBX3 to shuttle into the nucleus, synergistically enhances NCF2 transcription, and promotes BLCa angiogenesis and hematogenous metastasis by activating downstream NF-κB signaling. Our findings will develop prognosis prediction tools for BLCa patients and discover novel therapeutic biological targets for metastatic BLCa.

Clinical significance of prognostic nutritional index (PNI)-monocyte-to-lymphocyte ratio (MLR)-platelet (PLT) score on postoperative outcomes in non-metastatic clear cell renal cell carcinoma.

BACKGROUND: Prognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). METHODS: In this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients' outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier estimate and Cox regression models. RESULTS: The mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P < 0.001) and MFS (P < 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients. CONCLUSIONS: Our data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC.

Pain-Related Risk Factors Among Radiologic Stages of Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA). METHODS: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain. Knee OA severity was stratified into 4 categories according to the K/L system. Pain risk factors were evaluated using generalized ordinal logistic regression analysis, and a heatmap was created to compare differences in standardized regression coefficients between subgroups of patients with different knee OA severities. RESULTS: A total of 4,446 subjects were included in this study: 1,574 individuals without pain (35.4%), 1,138 individuals with mild pain (25.6%), and 1,734 individuals with moderate/severe pain (39.0%). For the entire population and subjects in the premorbid-stage subgroup, knee injury history, diabetes mellitus, depression, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and valgus malaligned knees were associated with more severe pain. Older age and stronger quadriceps muscles were associated with milder pain. As the disease progressed, the number of significant risk factors decreased. Only age and quadriceps muscle force remained significant in end-stage disease. CONCLUSION: Multiple factors are associated with pain in patients with knee OA. As the disease progresses, the number of significant risk factors gradually reduces. These findings suggest that strategies for managing pain related to knee OA should vary depending on radiographic grades.

Development and validation of a predictive model for diagnosing prostate cancer after transperineal prostate biopsy.

Objective: This study aimed to develop and validate a nomogram to predict the probability of prostate cancer (PCa) after transperineal prostate biopsy by combining patient clinical information and biomarkers. Methods: First, we retrospectively collected the clinicopathologic data from 475 patients who underwent prostate biopsy at our hospital between January 2019 to August 2021. Univariate and multivariate logistic regression analyses were used to select risk factors. Then, we established the nomogram prediction model based on the risk factors. The model performance was assessed by receiver operating characteristic (ROC) curves, calibration plots and the Hosmer-Lemeshow test. Decision curve analysis (DCA) was used to evaluate the net benefit of the model at different threshold probabilities. The model was validated in an independent cohort of 197 patients between September 2021 and June 2022. Results: The univariate and multivariate logistic regression analyses based on the development cohort indicated that the model should include the following factors: age (OR = 1.056, p = 0.001), NEUT (OR = 0.787, p = 0.008), HPR (OR = 0.139, p < 0.001), free/total (f/T) PSA (OR = 0.013, p = 0.015), and PI-RADS (OR = 3.356, p < 0.001). The calibration curve revealed great agreement. The internal nomogram validation showed that the C-index was 0.851 (95% CI 0.809-0.894). Additionally, the AUC was 0.851 (95% CI 0.809-0.894), and the Hosmer-Lemeshow test result presented p = 0.143 > 0.05. Finally, according to decision curve analysis, the model was clinically beneficial. Conclusion: Herein, we provided a nomogram combining patients' clinical data with biomarkers to help diagnose prostate cancers.

Comprehensive analysis of MFN2 as a prognostic biomarker associated with immune cell infiltration in renal clear cell carcinoma.

BACKGROUND: Treatment of advanced kidney renal clear cell carcinoma (KIRC) remains challenging in clinic. The functional role and prognostic significance of MFN2 in KIRC are still unclear. METHODS: In this study, we first performed a bioinformatic analysis to determine the expression level and prognostic value of MFN2 in KIRC using The Cancer Genome Atlas (TCGA) dataset, and then validated the MFN2 mRNA expression in our cohort of clinical tissue samples and cell lines of KIRC via RT-qPCR. Cox regression model was used to identify the independent prognostic factors. A nomogram was constructed to predict the prognosis of KIRC patients. Gene set enrichment analysis (GSEA) was performed to predict the involved functional pathways of MFN2 co-expressed genes. The association between MFN2 expression level and immune cell infiltration was assessed using the TIMER and the TIDISB databases. In addition, cell proliferation and migration abilities of two KIRC cell lines with MFN2 overexpression were evaluated by MTS and wound healing assays, respectively. RESULTS: Downregulation of MFN2 was observed in KIRC tissues and cell lines compared to the normal controls. Kaplan-Meier curve analysis indicated an inferior survival outcomes in KIRC patients with lower MFN2 expression, uncovering the tumor-suppressive role of MFN2 in KIRC. Cox regression results showed that higher MFN2 expression was one of the independent protective factors in KIRC. Besides, function predictive analysis revealed that MFN2 co-expressed genes were enriched in the biological processes of energy metabolism and autophagy. Moreover, MFN2 expression was observed to be significantly associated with immune cell infiltration and a variety of markers of tumor infiltrating immune cells (TIICs) including multiple immune checkpoints in KIRC tissues. Finally, MFN2 overexpression significantly inhibited cell proliferation and migration abilities of two KIRC cell lines examined. CONCLUSION: Generally, our data suggested that MFN2 may serve as a potential prognostic biomarker and therapeutic target in KIRC.

Flexible Ureteroscopic Lithotripsy Based on the Concept of Enhanced Recovery after Surgery: A Single-Centered Retrospective Study.

PURPOSE: To evaluate the efficacy of flexible ureteroscopic lithotripsy (FURSL) based on the concept of enhanced recovery after surgery (ERAS). MATERIALS AND METHODS: This study retrospectively analyzed 435 patients diagnosed with upper urinary calculi between 2017-2020 and categorized them into ERAS (ERAS management) and control groups (traditional management). The operative time, postoperative ambulation time, postoperative hospital stay, the total cost of hospitalization, postoperative complications, and stone removal rate between the two groups were subsequently compared. RESULTS: The FURSL procedure was successfully performed in 427 patients but failed in 4 patients of the ERAS group (n = 216) and 4 of the control group (n = 219). No postoperative complications occurred in either group except for fever and hematuria. There was no significant difference in postoperative fever and stone removal between the two groups (all P > .05). However, patients in the ERAS group had a shorter operative time, shorter postoperative ambulation time, less postoperative severe hematuria, shorter postoperative hospital stay, and lower total cost of hospitalization than those in the control group (all P < .05). CONCLUSION: FURSL, based on the concept of ERAS, is safe and reliable for the treatment of upper urinary calculi, with rapid postoperative recovery and a low cost of hospitalization. It is worthy of clinical promotion.

The inhibition of TRIM35-mediated TIGAR ubiquitination enhances mitochondrial fusion and alleviates renal ischemia-reperfusion injury.

Tripartite motif 35 (TRIM35) is a member of the tripartite motif protein family and has been recognized to play a key role in immune-inflammatory diseases. However, the role of TRIM35 in renal ischemia-reperfusion injury (IRI) remains unclear. Our study proved that knockdown of TRIM35 alleviates kidney IRI by inhibiting oxidative stress and enhancing mitochondrial fusion. In addition, our experimental results found that TRIM35 interacts with TP53-induced glycolysis and apoptosis regulator (TIGAR) and promotes the polyubiquitination of TIGAR and induces its degradation in the proteasome pathway. Furthermore, TIGAR knockdown significantly inhibited mitochondrial fusion. These results indicate that TRIM35 is a potential therapeutic target for renal IRI.

Allicin protects against renal ischemia-reperfusion injury by attenuating oxidative stress and apoptosis.

BACKGROUND: Studies have demonstrated that allicin may play critical roles in the procession of ischemia-reperfusion(I/R) injury. The purpose of this study was to investigate the protective effects of allicin on renal I/R injury by attenuating oxidative stress and apoptosis. METHODS: To establish a model of renal I/R, the right kidney underwent 12 h reperfusion after 45 min ischemia, allicin was administered intraperitoneally at concentrations of 40, 50 or 60 mg/kg. NRK-52E cells were treated with allicin at concentrations of 1, 3 or 5 µM in 24 h hypoxia/ 6 h reoxygenation(H/R) treatments. Indicators of HE, oxidative stress, apoptosis were measured to evaluate the effect of aliicin on renal I/R injury. RESULTS: Allicin protected renal I/R injury by ameliorating histological injury and decreasing the oxidative stress in renal tissues. Meanwhile, allicin significantly downregulated the expression of Bax and caspase-3, upregulated the expression of Bcl-2 in I/R renal tissues and H/R treated NRK-52E cells. CONCLUSIONS: Allicin may exert anti-apoptotic and antioxidative effects to promote renal function recovery in I/R renal tissues and H/R treated NRK-52E cells. Taken together, allicin may be a potential novel therapy option for future renal injury protection.

Application of 3D-printed prosthesis in revision surgery with large inflammatory pseudotumour and extensive bone defect: A case report.

BACKGROUND: Hip revision surgery is the final treatment option for the failure of artificial hip joints, but it is more difficult than the initial operation. For patients with hip joint loosening around the prosthesis combined with large inflammatory pseudotumours and large segment bone defects, hip revision is even more difficult, and clinical reports are rare. CASE SUMMARY: Male, 59 years old. The patient underwent left hip replacement 35 years ago and was now admitted to hospital due to massive masses in the left thigh, shortening of the left lower extremity, and pain and lameness of the left hip joint. X-ray, computed tomography and magnetic resonance imaging revealed prosthesis loosening, left acetabular bone defect (Parprosky IIIB type), and a bone defect of the left proximal femur (Parprosky IIIA type). Inflammatory pseudotumours were seen in the left hip and left thigh. Hip revision surgery was performed using a 3D-printed custom acetabular prosthesis was used for hip revision surgery, which was produced by Arcam Electron Beam Melting system with Electron Beam Melting technology. The operation was successful, and the patient was followed up regularly after the operation. The custom-made acetabular prosthesis was well matched, the inflammatory pseudotumour was completely removed, the postoperative hip prosthesis was stable, and the old greater trochanter fracture was well reduced and fixed. The patient was partially weight-bearing with crutches 3 mo after the operation and walked with full weight-bearing after 6 mo. The hip prosthesis was stable, and there was no recurrence of inflammatory pseudotumours at the last follow-up. The Visual Analogue Scale was 3, and the Harris hip score was 90. CONCLUSION: The use of 3D-printed personalized custom prostheses for complex hip revision surgery has satisfactory surgical results and has great clinical application value.

Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients.

PURPOSE: Identification of reliable postoperative indicators for accurately evaluating prognosis of clear cell renal cell carcinoma (ccRCC) patients remains an important clinical issue. This study determined the prognostic value of UBR5 expression in ccRCC patients by combining with CD163+ tumor-associated macrophages (TAMs) and the established clinical parameters. METHODS: The expression of UBR5 was analyzed in ccRCC patients from TCGA databases. A total of 310 ccRCC patients were randomly divided into the training and validation cohorts at a 3:2 or 1:1 ratio, and immunohistochemistry (IHC) and statistical analyses were performed to examine the prognostic value of UBR5 and CD163+ TAMs. RESULTS: UBR5 expression was commonly downregulated in human ccRCC specimens, which was associated with TNM stage, SSIGN, WHO/ISUP Grading and poor prognosis of ccRCC patients. In addition, UBR5 expression was negatively correlated with CD163 expression (a TAM marker) in ccRCC tissues, and combining expressions of UBR5 and CD163 better predicted worse overall survival and progression-free survival of ccRCC patients. Even after multivariable adjustment, UBR5, CD163, TNM stage and SSIGN appeared to be independent risk factors. By time-dependent c-index analysis, the integration of intratumoral UBR5 and CD163 achieved higher c-index value than UBR5, CD163, TNM stage or SSIGN alone in predicting ccRCC patients' prognosis. Moreover, the incorporation of both UBR5 and CD163 into the clinical indicators TNM stage or SSIGN exhibited highest c-index value. CONCLUSIONS: Integrating intratumoral UBR5 and CD163+ TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients' postoperative prognosis.

A universal electrochemical lithiation-delithiation method to prepare low-crystalline metal oxides for high-performance hybrid supercapacitors.

The electrochemical performance of transition metal oxides (TMOs) for hybrid supercapacitors has been optimized through various methods in previous reports. However, most previous research was mainly focused on well-crystalline TMOs. Herein, the electrochemical lithiation-delithiation method was performed to synthesise low-crystallinity TMOs for hybrid supercapacitors. It was found that the lithiation-delithiation process can significantly improve the electrochemical performance of "conversion-type" TMOs, such as CoO, NiO, etc. The as-prepared low-crystallinity CoO exhibits high specific capacitance of 2154.1 F g-1 (299.2 mA h g-1) at 0.8 A g-1, outstanding rate capacitance retention of 63.9% even at 22.4 A g-1 and excellent cycling stability with 90.5% retention even after 10 000 cycles. When assembled as hybrid supercapacitors using active carbon (AC) as the active material of the negative electrode, the devices show a high energy density of 50.9 W h kg-1 at 0.73 kW kg-1. Another low-crystallinity NiO prepared by the same method also possesses a much higher specific capacitance of 2317.6 F g-1 (302.6 mA h g-1) compared to that for pristine commercial NiO of 497.2 F g-1 at 1 A g-1. The improved energy storage performance of the low-crystallinity metal oxides can be ascribed to the disorder of as-prepared low-crystallinity metal oxides and interior 3D-connected channels originating from the lithiation-delithiation process. This method may open new opportunities for scalable and facile synthesis of low-crystallinity metal oxides for high-performance hybrid supercapacitors.

[Role of the lncRNA H19/ microRNA-203a/PTEN axis in ischemia-reperfusion injury of mouse GC-1 cells and its mechanism].

OBJECTIVE: To investigate the expression of long non-coding RNA (lncRNA) H19 in mouse GC-1 cells in vitro and its effects on the proliferation and apoptosis of GC-1 cells. METHODS: We established an in vitro hypoxia-reoxygenation model in GC-1 cells and detected the expression of lncRNA H19 in the GC-1 cells at different time points of reoxygenation injury by qRT-PCR. We determined the effects of silencing lncRNA H19 on the proliferation and apoptosis of the GC-1 cells by MTT and flow cytometry, the expressions of apoptosis-related proteins Bax and caspase-3 in the GC-1 cells by Western blot, and the expressions of microRNA-203a and PTEN by qRT-PCR and Western blot, respectively. RESULTS: With the prolonging of the time of reoxygenation injury, the expression of lncRNA H19 was increased significantly in the GC-1 cells and peaked at 3-hour hypoxia and 12-hour reoxygenation, but that of microRNA-203a markedly decreased. Silencing lncRNA H19 enhanced the proliferation and inhibited the apoptosis of the GC-1 cells, and up-regulated the expression of microRNA-203a and down-regulated that of PTEN in the GC-1 cells. CONCLUSIONS: LncRNA H19 is highly expressed in GC-1 cells in vitro, which may influence the proliferation and apoptosis of GC-1 cells by regulating the microRNA-203a /PTEN signaling pathway.

A rare entity of Primary Ewing sarcoma in kidney.

BACKGROUND: Ewing sarcoma (ES) or primitive neuroectodermal tumors (PNET) represents a spectrum of poorly differentiated and aggressive malignancies. It rarely arises from the kidney and accounts for less than 1% of renal mass. Given the uncharacteristic clinical symptoms and imaging features, renal Ewing sarcoma (RES) is often diagnosed by postoperative pathology. CASE PRESENTATION: Herein, we depicted a case of RES, which was administrated in our institution by chief complaints of intermittent left plank pain and palpable abdominal mass. We demonstrated the aggressive behavior of this renal malignancy and summarized its therapeutic modalities and outcomes. CONCLUSION: The diagnosis of RES relies on integrated analysis including histomorphology, immunohistochemical staining and confirmation of molecular-genetic testing. Despite the surgery and adjuvant therapy, optimized and potent therapeutic regimes are still urgently needed to improve the poor prognosis of RES.

Levofloxacin: Is It Still Suitable as an Empirically Used Antibiotic During the Perioperative Period of Flexible Ureteroscopic Lithotripsy? A Single-center Experience with 754 Patients.

PURPOSE: To determine the empirical usage of antibiotics and analyze the pathogen spectrum during the perioperative period of flexible ureteroscopic lithotripsy (FURSL) with a focus on levofloxacin. MATERIALS AND METHODS: This retrospective analysis included 754 patients who underwent FURSL successfully in our hospital from January 2015 to July 2019. All patients were indicated urine cultures and prescribed antibiotics during the perioperative period. Patients with negative preoperative urine cultures were divided into levofloxacin (LVXG) and non-levofloxacin groups (NLVXG) based on the empirical use of antibiotics. Operative time, the length of postoperative hospital stays and total hospital stays, total hospitalization costs, postoperative fever rate and removal rate of stones were compared. Patients with positive urine cultures were analyzed for  pathogen distribution and antibiotic resistance. RESULTS: In the empirical use of antibiotics among 541 cases with negative urine cultures, the prescription rate of levofloxacin was 68.95%. Compared to that in NLVXG, LVXG had a lower cost of antibiotics but higher postoperative fever rate and longer hospital stay. There were no significant differences in operative time, the total hospitalization costs and the removal rate of stones between the two groups. The top two common pathogens were Escherichia coli (36.11%) and Enterococcus faecalis (24.07%), with resistance rates of 74.36% and 71.15% to levofloxacin, respectively. CONCLUSION: Levofloxacin might be no longer suitable as the first-line choice of clinical experience when performing FURSL in our center.

LncRNA PLAC2 upregulates miR-663 to downregulate TGF-ß1 and suppress bladder cancer cell migration and invasion.

BACKGROUND: The roles of lncRNA PLAC2 in bladder cancer (BC) were explored. METHODS: The expression of PLAC2 in two types of tissue of BC patients was detected by RT-qPCR and the expression data were compared by paired t test. The 56 patients were staged according to the AJCC criteria, and 12, 15, 15 and 14 cases were classified into stage I-IV, respectively. The expression of TGF-ß1 and miR-663 in BC tissues were also detected by RT-qPCR experiments. RESULTS: Our data showed that the expression levels of PLAC2 were significantly lower in BC tissues than that in non-cancer tissues. The expression of PLAC2 was not affect by clinical stages and low expression levels of PLAC2 predicted lower survival rate. The expression of PLAC2 was positively correlated with miR-663 and inversely correlated with TGF-ß1 in BC tissues. In BC cells, downregulated TGF-ß1 and upregulated miR-663 were observed after the overexpression of PLAC2. Overexpression of PLAC2 also resulted in suppressed invasion and migration of BC cells. Overexpression of miR-663 resulted in downregulated TGF-ß1 but did not affect the expression of PLAC2. Overexpression of TGF-ß1 reduced the inhibitory effects of overexpression of PLAC2 and miR-663 on cell migration and invasion. CONCLUSION: PLAC2 can upregulate miR-663 to downregulate TGF-ß1 and suppress BC cell migration and invasion.

Leflunomide Inhibits Proliferation and Induces Apoptosis via Suppressing Autophagy and PI3K/Akt Signaling Pathway in Human Bladder Cancer Cells.

INTRODUCTION: Bladder cancer is a lethal human malignancy. Currently, treatment for bladder cancer is limited. The anti-tumor effects of leflunomide have attracted much more concern in multiple human cancers. MATERIALS AND METHODS: This study evaluated the anti-tumor effects of leflunomide on cell viability, colony formation, apoptosis, and cell cycle in two human bladder carcinoma cell lines, 5637 and T24. Meanwhile, the underlying mechanism including PI3K/Akt signaling pathway and autophagy modulation was also identified. RESULTS: Leflunomide markedly inhibited the growth of both bladder cancer cell lines and induced apoptosis and cell cycle arrest in S phase. The phosphorylation levels of Akt and P70S6K in both cell lines were significantly down-regulated with leflunomide treatment. Furthermore, the deceased formation of autophagosomes and the accumulation of LC3II and P62 suggested the blockade of autophagy by leflunomide. Modulation of autophagy with rapamycin and chloroquine markedly attenuated and enhanced the cytostatic effects of leflunomide, respectively. CONCLUSION: Leflunomide significantly reduced the cell viability of bladder cancer cells via inducing apoptosis and cell cycle arrest and suppressing the PI3K/Akt signaling pathway. In addition, the blockade of autophagy was observed, and autophagy inhibition enhanced leflunomide-mediating anti-tumor effects. Our data presented here offer novel ideas for comprehensive therapeutic regimes on bladder cancer.

Dexmedetomidine Attenuates High Glucose-induced HK-2 Epithelial-mesenchymal Transition by Inhibiting AKT and ERK.

OBJECTIVE: To explore the protective effects of dexmedetomidine (Dex) against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms. METHODS: HK-2 cells were exposed to either glucose or glucose+Dex for 6 h. The production of ROS, morphology of HK-2 cells, and cell cycle were detected. Moreover, the expression of AKT, p-AKT, ERK, p-ERK, PI3K, E-Cadherin, Claudin-1, and α-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126. RESULTS: Compared with HK-2 cells exposed to high level of glucose, the HK-2 cells exposed to both high level of glucose and Dex showed: (1) lower level of ROS production; (2) cell morphology was complete; (3) more cells in G1 phase; (4) lower expression of p-AKT, p-ERK and α-SMA, higher expression of E-Cadherin and Claudin-1. PI3K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT, p-ERK and α-SMA, and increased the expression of E-Cadherin and Claudin-1. CONCLUSION: Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK.

Micropercutaneous versus Retrograde Intrarenal Surgery for the Management of Moderately Sized Kidney Stones: A Systematic Review and Meta-Analysis.

INTRODUCTION: To compare the effect of micropercutaneous surgery (microperc) and retrograde intrarenal surgery (RIRS) in the management of moderately size kidney stones. METHODS: A systematic literature search was conducted in March 2019 using PubMed, Google Scholar, Web of Science, Embase, the Cochrane Library, and Medline to identify relevant studies. A subgroup analysis was performed to compare microperc with RIRS in patients with lower-pole stones (LPS) and non-LPS (NLPS), respectively. RESULTS: Three randomized controlled trials (RCTs) and 4 non-RCTs were analyzed. Microperc provided a significantly lower rate of double-J stent insertion (p < 0.00001) but a larger decrease in hemoglobin levels (p = 0.0002). In contrast, RIRS led to a shorter hospital stay (p = 0.01) and a lower stone-free rate (SFR) (p = 0.03). IN the subgroup analysis, RIRS provided a significantly lower drop in hemoglobin drop than microperc in patients with LPSs (p = 0.0003). Microperc showed a longer operative time (p = 0.03), longer hospital stay (p = 0.04), and greater drop in hemoglobin (p = 0.04) in patients with NLPS. CONCLUSIONS: Microperc is associated with fewer double-J stent insertions and higher SFR at the expense of a greater drop in hemoglobin and longer hospital stay. Given the differences between the procedures, urologists should synthesize the individual characteristics of patients and unique advantages of these therapies so as to choose the optimal treatment for individual patients.

Effect of NRP1 gene knockout on process of radiationinduced pulmonary fibrosis and its mechanism / 吉林大学学报(医学版)

Objective: To observe the effect of neuroopilin-1 (NRP1) gene on the process of radiation-induced pulmonary fibrosis (RIPF), and to explore its roles in the occurrence and development of epithelial-mesenchymal transition (EMT) mediated by Wnt/fi-catenin pathway tail identification was performed in and TGF-β1/Smads pathway, and extracellular matrix (ECM) deposition. Methods: The Cre-LoxP recombinase system was used to construct the transgenic C57BL/6J mice with NRP1 gene specific knockout in alveolar type II epithelial cells (AT-II) and the mice. A total of 160 mice were randomly divided into 4-week group, 8-week group, 16-week group and 24-week group. In each group, the mice were randomly divided into wild type (Con) group, wild type+irradiation (IR) group, NRP1 gene-specific knockout (KO-Con) group, NRP1 gene-specific knockout+irradiation (KO+IR) group according to the method of random number table; there were 10 mice per group. In KO-Con and KO + IR groups, the NRP1 gene was specifically knocked out in the AT-II cells by intraperitoneal injection of tamoxifen, and the mouse models of RTPF were established by 20 Gy total thoracic irradiation in IR group and KO+IR group. After the models were constructed, HE staining and Masson staining were used to verify whether the models were successfully constructed. Immunohistochemistry (IHC) method was used to detect the type I collagen (Col I) and crsmooth muscle actin α-SMA) protein expression levels; Western blotting method was performed to detect the NRP1, β-catenin, TGF-β1, and Smad2 protein expression levels in the lung tissue of the mice; Quantitative fluorensence real-time polymerase chain reaction (qRT-PCR) method was used to detect the expression levels of NRP1, Col I, α-SMA, β-catenin, TGF-βl, Smad2, E-cadherin, N-cadherin, and Vimentin mRNA in the lung tissue of the mice. Results: The results of HE and Masson staining showed the RTPF models were successfully established, and the lung tissue of the mice in IR group mainly showed the pathomorphology of radiation pneumonitis. Compared with Con group, the protein and mRNA expression levels of NRP1 in the lung tissue of the mice in IR group were gradually increased with the prolongation of time (P<0.05), and reached the highest at 24 weeks (P<0.01). Compared with Con group, the expression levels of Col I, α-SMA, β-catenin, TGF-β1, and Smad2 proteins and mRNA in the lung tissue of the mice in IR group and KO+IR group were increased gradually with the prolongation of time (P<0.05 or P<0.01). Compared with IR group, the expression levels of Col I, α-SMA, β-catenin, TGF-β1, and Smad2 protein and mRNA in the lung tissue of the mice in KO+IR group were significantly decreased (P<0.05 or P<0.01), but they were higher than those in Con group (P<0.05 or P<0.01). Compared with Con group, the expression levels of the epithelial cell marker E-Cadherin mRNA in the lung tissue of the mice in IR group and KO+IR group were gradually decreased with the prolongation of time (P< 0.01), and the expression levels of the interstitial cell markers N-Cadherin and Vimentin were increased (P<0.05 or P<0.01), but the expression levels of E-cadhern mRNA in the lung tissue of the mice in KO-IR group were significantly higher than those in IR group (P<0.05 or P<0.01), and the expression levels of N-Cadherin and Vimentin mRNA in the lung tissue of the mice in KO + IR group at each time point were lower than those in IR group (P<0.05 or P<0.01). Conclusion: Knockout of NRP1 gene can inhibit the occurrence and development of RTPF, and its mechanism may be involved in regulating the expressions of Wnt/fi-catenin and TGF-β1/Smads signaling pathways in the lung tissue and inhibiting the EMT process in the mice.