ROUX-en-Y gastric bypass surgery improves metabolic syndrome-related erectile dysfunction in mice via the IRS-1/PI3K/AKT/eNOS pathway.

Objective: Although many clinical studies have shown that ROUX-en-Y gastric bypass (RYGB) surgery significantly improves metabolic syndrome-related erectile dysfunction (MED), the role and mechanism are unclear. Aim: In this study we used a mouse model to explore how RYGB improves MED induced by a high-fat diet (HFD). Methods: We established a mouse model of metabolic syndrome by feeding an HFD for 16 weeks. The mice were randomly assigned to the standard chow diet (SCD), HFD, or RYGB groups. Body weight, fasting blood glucose, plasma insulin, and total plasma cholesterol were analyzed. Erectile responses were evaluated by determining the mean systolic blood pressure and the intracavernosal pressure (ICP). Penile histologic examination (Masson's trichrome and immunohistochemical stain) and Western blot were performed. Result: Compared with the SCD group, the ICP in the sham group was significantly lower, and the ICP of the RYGB was significantly increased. Masson's trichrome and immunohistochemical staining showed that the content of endothelium and smooth muscle in the corpus cavernosum of mice with MED was significantly reduced. Western blot analysis showed a significant decrease in α-smooth muscle actin and a significant increase in osteopontin in penile tissue in the sham group, which was improved by RYGB surgery. Furthermore, RYGB significantly increased IRS-1/PI3K/Akt/eNOS phosphorylation. Clinical Translation: In this study we explored the mechanism of bariatric surgery to improve erectile dysfunction associated with metabolic syndrome and provided a theoretical basis for clinical research. Strengths and Limitations: First, we did not investigate the mechanism by which RYGB affects the IRS-1/PI3K/Akt/eNOS signaling pathway. Second, the effect of the IRS-1/PI3K/Akt/eNOS signaling pathway on the function of corpus cavernosum endothelial cells and smooth muscle cells remains to be investigated in cellular studies. Conclusion: This study demonstrated that RYGB may not only improve metabolic parameters but also restore erectile function in MED patients. The mechanism of the therapeutic effect of RYGB may be reactivation of the IRS-1/PI3K/Akt/eNOS pathway.

Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy.

Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8+ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes.

Transarterial Chemoembolization Followed by Hepatic Arterial Infusion Chemotherapy Combined a Tyrosine Kinase Inhibitor for Treatment of Large Hepatocellular Carcinoma.

OBJECTIVE: Evaluate the efficacy and safety of transarterial chemoembolization (TACE) sequential with hepatic arterial infusion chemotherapy (HAIC) and a tyrosine kinase inhibitor (TKI) for unresectable large hepatocellular carcinoma (HCC). METHODS: Patients with HCC size > 70 mm were included. They received 1-3 cycles of TACE and sequential HAIC every 3-6 weeks for 2-6 cycles, with each cycle given over a period of 48 hours (oxaliplatin plus fluorouracil/leucovorin). Patients also received sorafenib or lenvatinib beginning at the first TACE cycle and continuing until disease progression. Objective response rate (ORR) at 3 months was the primary endpoint. Progression-free survival (PFS) and safety were the secondary endpoints. RESULTS: From January 2020 to December 2020, 41 patients were included, who were divided into the drug-eluting bead TACE (DEB-TACE) group (n=13) and conventional TACE (cTACE) group (n=28). The overall ORR was 56.1% (23/41) using mRECIST criteria and 34.1% (14/41) using RECIST1.1 criteria. The median PFS of the cohort was 8 months. The ORR of the DEB-TACE group was 76.9% (10/13) vs. 46.4% (13/28) for the cTACE group (p = 0.06). The median PFS of the DEBTACE group was 12 months, and 6 months in the cTACE group (p = 0.09). Conversion hepatectomy was performed in 2 patients in the DEB-TACE group (15.4%), and in 3 patients in the cTACE group (10.7%). ALT/AST elevated, hypertension, nausea, and vomiting were the common treatment related adverse events. There was no treatment related death. CONCLUSION: TACE sequential with HAIC combined a TKI is a well-tolerated and promising tripletherapy for large, unresectable HCC.

XperCT facilitates sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients.

OBJECTIVE: Our objective was to evaluate the feasibility of XperCT combined fluoroscopy to guide sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients. METHODS: The records of hemodialysis patients with chronic thoracic venous occlusive disease who received endovascular sharp recanalization after conventional techniques failed were retrospectively reviewed. The sharp devices used for recanalization included the stiff end of a guidewire, Chiba biopsy needle, RUPS-100 set, and transseptal needle. The needle was advanced toward a target placed at the opposite end of the occlusion and was guided by fluoroscopy and/or XperCT. While the guidewire crossed the occlusion, endovascular procedures such as percutaneous angioplasty were performed for the treatment of the occlusion. RESULTS: The analysis included 32 sharp thoracic vein recanalization procedures in 29 patients. Two attempts in one patient failed, and in one patient the first attempt failed but the second attempt was successful. In one patient, two separate successful procedures were performed, and the other 26 procedures in 26 patients were successful. The overall technical success rate of sharp recanalization was 90%. The mean number of puncture attempts in the combined group was less than that of the fluoroscopy-guided alone group (2 vs 5, p < 0.05). The success rate of sharp recanalization in the combined group was higher (100% vs 86%), and the recanalization time (28.5 min vs 36 min, p > 0.05) was no different. There was no statistical difference in procedure-related complications between the groups. CONCLUSION: XperCT can facilitate sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients.

Construction of cellulose-based highly sensitive extended-gate field effect chiral sensor.

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13 M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.

Ferritin Nanocaged Doxorubicin Potentiates Chemo-Immunotherapy against Hepatocellular Carcinoma via Immunogenic Cell Death.

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with >30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.

Mediastinal Hepatoid Adenocarcinoma Treated With Arterial Interventional Therapy: A Case Report and Review of Literature.

Hepatoid adenocarcinoma (HAC) is an extremely rare extrahepatic carcinoma, which is pathologically featured by hepatocellular carcinoma (HCC) and marked by producing alpha-fetoprotein (AFP). HAC of mediastinum is extremely rare. For inoperable patients, the curative treatment options have not been established, and the outcome of HAC is usually poor. Here, we present a case of mediastinal HAC with normal serum AFP level who achieved well-controlled and good response after local-regional interventional approach combined with systemic PD-1 inhibitor. A 53-year-old male who complained of chest pain was admitted to our hospital in February 2021. A chest CT scan revealed several tumors in his mediastinum. The laboratory data showed normal serum AFP level. HAC was diagnosed through pathological assessment of biopsy. Surgery was not available due to the infiltration of sternum. Local regional FOLFOX chemotherapy was given by transarterial infusion, followed by transcatheter arterial chemoembolization, and thereafter combined with systemic anti-PD-1 treatment. The patient achieved favorable disease control and apparent symptom relief. So transarterial interventional therapy combined immunotherapy may be a possible and promising treatment for mediastinal HAC.

Transradial versus Transfemoral Access for Patients with Liver Cancer Undergoing Hepatic Arterial Infusion Chemotherapy: Patient Experience and Procedural Complications.

PURPOSE: To determine whether transradial access (TRA) is a more favorable and safe method for hepatic arterial infusion chemotherapy (HAIC) than transfemoral access (TFA). MATERIALS AND METHODS: Retrospective and prospective cohorts of patients with liver cancer were included. Sixty-seven patients in the retrospective cohort were divided into 2 groups: (a) TRA-HAIC (n = 24) and (b) TFA-HAIC (n = 43). Another 33 patients were prospectively enrolled to receive both TRA and TFA for HAIC in a crossover design. Prolonged arterial access was required for up to 48 hours. The primary endpoint was quality of life (QOL) using the visual analog scale. The secondary endpoints mainly included procedural success, adverse events, and operation time. RESULTS: Patient QOL measures revealed significantly lower scores of indices in the TRA-HAIC group than in the TFA-HAIC group in the retrospective cohort (all P < .001). The significant improvement of the QOL indices by TRA-HAIC, such as overall discomfort (P = .019) and pain at the access site (P = .018), was validated in the prospective cohort. The satisfaction scores were significantly higher in the TRA-HAIC group than in the TFA-HAIC group, and patients preferred TRA-HAIC (P < .001). Radial artery occlusion (RAO) as an access-related adverse event occurred more frequently in both the retrospective and prospective cohorts (38% and 33%, P < .001 and P = .001, respectively). Notably, the multivariate analysis of RAO-associated factors showed that enoxaparin use was significantly correlated with a reduced risk of postprocedural RAO (P = .036). CONCLUSIONS: TRA was superior to TFA in patient experience. However, because of the high incidence of access-related adverse events, especially for RAO with a total incidence of 35%, strategies should be optimized for patients to benefit from TRA in future procedures.

Sharp recanalization for treatment of central venous occlusive disease in hemodialysis patients.

BACKGROUND: The purpose of the present study was to evaluate the technical feasibility and safety of sharp recanalization for central venous occlusive disease (CVOD) in patients requiring hemodialysis. METHODS: Patients with CVOD requiring hemodialysis who had undergone endovascular recanalization using sharp devices, including the stiff end of a guidewire, Chiba needle, or RUS-100 to cross occluded segments after conventional techniques had failed were included. The needle was guided toward a target placed at the opposite end of the occlusion. Although the guidewire was passed though the occlusion, subsequent procedures such as percutaneous transluminal angioplasty could be performed. RESULTS: A total of 27 sharp recanalization procedures in 25 patients were performed. Two attempts failed, 1 patient had undergone two separate successful procedures, and 23 procedures in 23 patients were successful. The overall technique success was 92.6%. The stiff end of a guidewire was the first choice for all the procedures, and recanalization was achieved in 18 patients (66.7%). A Chiba biopsy needle was used in six procedures (22.2%), with 100% technical success. A RUPS-100 set was used in two procedures (7.4%), with one aborted because of concern for complications. The occlusion was subsequently crossed using a Chiba needle. Four minor adverse events (two of mediastinal hematoma and two of chest pain) had occurred, and two major adverse events (pericardial tamponade and acute pleural effusion in one patient [4%], treated with the guidewire stiff-end technique, who recovered after drainage) had occurred. CONCLUSIONS: Sharp recanalization is safe and feasible with high technical success for CVOD in patients requiring hemodialysis who cannot be recanalized using conventional techniques.

microRNA-375 inhibits the malignant behaviors of hepatic carcinoma cells by targeting NCAPG2.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Emerging evidence has revealed the vital functions of microRNAs (miRNAs) in cancer malignant progressions. miR-375 has been verified to serve as an antioncogene in tumorigenesis and a potential therapeutic target in various types of cancer. In this study, we aimed to determine the role of miR-375 in the regulation of chemoresistance and metastasis of HCC. Differentially expressed miR-375 and NCAPG2 were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-375 in HCC tissues and cell lines. miR-375 mimics and NCAPG2-overexpression were transfected into HepG2 and Huh7 cells to establish miR-375 overexpression models. Cell Counting Kit-8, Transwell, and flow cytometry experiments were conducted to monitor cell proliferation, migration, and apoptosis. The targeting relationship between miR-375 and non-SMC condensin II complex subunit G 2 (NCAPG2) was determined by qRT-PCR, western blot, and luciferase reporter gene assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using Gene Set Enrichment Analysis (GSEA). The pathway enrichment analysis was used to predict the potential pathways for further study. miR-375 was significantly downregulated in HCC tissues and cells compared to adjacent tissue and normal hepatocyte cell line respectively while NCAPG2 was upregulated. The targeting relationship was verified by luciferase reporting assay, and miR-375 could target the 3'UTR of NCAPG2 mRNA and effectively suppress NCAPG2 protein expression. Replenishing of miR-375 significantly repressed HCC cell proliferation and migration, and induced cell apoptosis. Overexpression of NCAPG2 recovered those biological abilities in miR-375 overexpressed cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating NCAPG2. Replenishing of miR-375 or knockout of NCAPG2 could be therapeutically exploited for HCC.

The earlier, the better: The beneficial effect of different timepoints of the preoperative transarterial embolization on ameliorating operative blood loss and operative time for carotid body tumors.

BACKGROUND: To explore the effect of the optimal time interval from preoperative transarterial embolization to surgery of carotid body tumors by analyzing surgery-related indicators. METHODS: This single-center retrospective review included 103 patients and 108 carotid body tumor resections performed between June 2010 and June 2020. All carotid body tumors were divided into three groups based on interval time between transarterial embolization and surgery: 1-day group (G1), 2-day group (G2), and 3-day group (G3). Demographics, inflammatory biomarkers, periprocedural details, and postoperative outcomes were analyzed. RESULTS: Among 103 patients, 48.54% were women, and the mean age was 37.07 years. The tumor sizes were 43.83, 44.31, and 42.84 mm in G1, G2, and G3, respectively, and the blood loss and operative time were 163.68, 331.54, and 683.68 mL, and 182.32, 216.31, and 280.79 mins with the prolonged time interval, respectively. Compared with pretransarterial embolization, the expression of white blood cells (109/L) and neutrophils (109/L) were obviously increased post-transarterial embolization in the three groups (G1: white blood cells 6.81 vs 9.32; neutrophils 0.54 vs 0.74, all P < .05. G2: white blood cells 7.19 vs 10.01, P = .118; neutrophils 0.54 vs 0.77, P < .05. G3: white blood cells 7.08 v. 12.37; neutrophils 0.59 vs 0.80, all P < .05), and those in G3 were significantly higher than those in G1. The incidences of revascularization, which was 30.26%, 53.85%, and 42.10%, and adverse events (26.32%, 30.77%, and 21.05%) were not significantly different among G1, G2, and G3. CONCLUSION: The optimal time interval between preoperative transarterial embolization and surgical resection resulted as 1 day as patients in this group showed obvious lower blood loss and shorter duration of operation than patients in other groups. Both inflammation and recanalization provided support for these results at some extent.

Prognostic value of splenic volume in hepatocellular carcinoma patients receiving transarterial chemoembolization.

BACKGROUND: Liver function is a key determinant for the survival of hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). However, establishing robust prognostic indicators for liver insufficiencies and patient survival remains an unmet demand. This retrospective study evaluated the prognostic value of splenic volume (SV) in HCC patients undergoing TACE. METHODS: A total of 67 HCC patients who underwent at least two consecutive TACE procedures were retrospectively included in this study. Comprehensive clinical information and follow-up data were collected, and the SV was measured based on dynamic contrast enhanced images. Risk factors of SV enlargement were assessed. The prognostic value of SV on survival was analyzed and compared with Child-Pugh (CP) classification and albumin-bilirubin (ALBI) grade. RESULTS: The baseline SV was 299.74±143.63 cm3, and showed a moderate and statistically significant correlation with CP classification (R=0.31, P<0.05). The SV increased remarkably after the first and second TACE procedures (330.16±155.38 cm3, P<0.01, and 355.63±164.26 cm3, P<0.01, respectively). In survival analysis, the optimal cut-off value of SV was determined as 373 cm3 using X-tile software, and the patients were divided into the small SV group and the large SV groups accordingly. Based on the pre-TACE SV, the median overall survival (mOS) for patients in the small SV group and the large SV group was 458 days and 249 days, respectively (P<0.05). After the first and second TACE, the mOS in the small SV group and the large SV group were 454 vs. 266 days (P<0.05) and 526 vs. 266 days (P<0.05), respectively. No prognostic value of CP classification and ALBI grade was identified for these patients. Furthermore, there were no significant differences between the small and large SV groups in age, tumor stage, and ALBI grade, except for CP classification (P<0.05). CONCLUSIONS: SV was correlated with CP classification and was a robust predictor for HCC patients undergoing TACE treatment.

Comparative analysis of the clinical effect and safety of Laparoscopic Radical Cystectomy + Orthotopic Ileal Neobladder and Open Surgery.

OBJECTIVES: To explore the clinical effect and safety of laparoscopic radical cystectomy + orthotopic ileal neobladder and open surgery. METHODS: The study was conducted at Jingzhou First People's Hospital from January 2017 to July 2018. In this study 87 patients undergoing radical cystectomy + orthotopic ileal neobladder were chosen and classified into an observation group (48 cases) and a control group (39 cases) according to the surgical methods. The observation group underwent laparoscopic surgery, while the control group underwent open surgery. Perioperative period and prognostic conditions were compared in both groups. RESULTS: The intraoperative bleeding amount obviously decreased. The recovery time of gastroenteric function and postoperative hospitalization time were significantly shortened. Postoperative pain was significantly alleviated. Compared with the control group, the observation group showed significant differences (P<0.05). The time, amount and difference in pelvic lymph node dissection in both groups were not significantly different (P>0.05). The differences in both groups in terms of the daytime/nighttime urinary continence rate, maximum urinary flow rate, internal bladder pressure, maximum bladder pressure during urination, internal urethral pressure, bladder capacity, and residual urine volume six months after the operation were not statistically significant (P>0.05). There was no significant difference in postoperative complications, including urinary fistula, bleeding, urinary tract infection, pulmonary infection, dysuria, lymphatic leakage, ureterostenosis, or relapse (P>0.05). The ileus incidence rate in the observation group was obviously lower than that in the control group, and the difference was statistically significant (P<0.05). CONCLUSION: Laparoscopic radical cystectomy + orthotopic ileal neobladder has the characteristics of limited trauma, a minimal amount of bleeding and a fast recovery. The functions of orthotopic neobladders are good, and the occurrence rate of postoperative complications is low. In addition, body immunity is protected. Hence, this procedure deserves to be promoted clinically.

A versatile UCST-type composite microsphere for image-guided chemoembolization and photothermal therapy against liver cancer.

The development of novel chemoembolization agents to improve the treatment efficacy of transarterial chemoembolization (TACE) against liver cancer remains an urgent need in clinical practice. Herein, a versatile composite microsphere with upper critical solution temperature (UCST) properties was prepared to encapsulate polydopamine coated superparamagnetic iron oxide nanoparticles (SPION@PDA) and doxorubicin for simultaneous chemoembolization and photothermal therapy. The microspheres were spherical with an average diameter of 100-300 µm and exhibited favorable drug loading capability as well as strong photothermal effect. Strikingly, synergistic enhancement of photothermal therapy and chemotherapy against chemoresistant liver cancer cells was achieved. The in vivo therapeutic efficacy and safety evaluations were performed using rabbit VX2 liver tumor models. It was revealed that a single treatment of the combination of TACE and photothermal procedure resulted in 87.5% complete response and 12.5% partial response for the microsphere group, whereas all tumors in the control group progressed rapidly. Contrast-enhanced computed tomography (CT) evaluation indicated that the tumor diameter decreased by 91.5% after treatment, while that in the control group increased by 86.5%. The pathology-proven tumor necrotic rate was 87.2%, which significantly surpassed that of 65.2% in the control group. Furthermore, serum liver enzyme and biochemical studies indicated a temporary liver injury which can be fully recovered. Our findings demonstrated that this microsphere may be advantageous for enhancing therapeutic efficacy of TACE against liver cancer.

Research on mechanism of miR-130a in regulating autophagy of bladder cancer cells through CYLD.

PURPOSE: The study aimed to explore the regulatory mechanism of micro ribonucleic acid (miR)-130a in the autophagy of bladder cancer cells through cylindromatosis (CYLD). METHODS: Human bladder cancer T24 cell line was used as the objects of the study. After miR-130a was knocked down using small-interfering RNA (siRNA) in T24 cell line, the changes in expressions of miR-130a and CYLD in each group were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The cell proliferation in each group was detected using cell counting kit-8 (CCK8) assay and flow cytometry. The changes in mRNA and protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 were determined using qRT-PCR and Western blotting. The autolysosomes were detected through acridine orange (AO)/ethidium staining bromide (ER) staining. Moreover, CYLD was knocked down using siRNA, and then the changes in mRNA expressions of miR-130a, LC3 and Beclin1 in each group were detected through qRT-PCR. RESULTS: After interference in miR-130a with siRNA, miR-130a-siRNA group had a significantly lower mRNA expression of miR-130a compared with NC-siRNA group and a significantly higher mRNA expression of CYLD (p<0.05), obviously inhibited cell proliferation (p<0.05), and decreased significantly mRNA and protein expressions of LC3 showing Beclin1 (p<0.05), and an evidently smaller number of autolysosomes. After knockdown of CYLD using siRNA, the mRNA expression of miR-130a had no significant changes (p>0.05), while the mRNA expressions of LC3 and Beclin1 declined significantly in CYLD-siRNA group compared with those in NC-siRNA group (p<0.05). CONCLUSION: MiR-130 can promote the autophagy of bladder cancer cells through regulating CYLD, thus facilitating the proliferation of tumor cells.

Comparative study on the curative effect of laparoscopic nephron sparing surgery and renal functions under selective segmental renal artery clamping and main renal artery clamping.

OBJECTIVE: To discuss the clinical effect and safety evaluation of laparoscopic nephron sparing surgery (LNSS) under selective segmental renal artery clamping (SSRAC) and main renal artery clamping (MRAC). METHODS: Eighty-four patients with T1 localized renal tumors who were admitted and treated from October 2017 to October 2018 were retrospectively analyzed, and they were classified into the S group (42 patients) and M group (42 patients). The patients in the S group received LNSS under SSRAC, while the patients in the M group received LNSS under MRAC. The duration of the operation, amount of intraoperative blood loss, intraoperative warm ischemia time, duration of postoperative hospital stay and positive rate of incisal edge; the serum creatinine and blood urea nitrogen values before and after the operation; and the occurrence rates of intraoperative and postoperative complications were compared. RESULTS: All operations were completed smoothly. No patients had a positive incisal edge, and no patients were converted to MRAC during the operation. The duration of the operation and the amount of intraoperative blood loss increased in the S group compared with the M group. The differences were statistically significant (P <0.05). The differences in the intraoperative warm ischemia time, postoperative drainage and duration of postoperative hospital stay in both groups had no statistical significance (P >0.05). The differences in serum creatinine (SCr) and blood urea nitrogen (BUN) in both groups before the operation had no statistical significance (P >0.05). The SCr and BUN levels significantly increased 1 d and 1 m after the operation. The SCr and BUN levels 1 d and 1 m after the operation were significantly lower in the S group than in the M group, and the differences were statistically significant (P <0.05). The differences in the occurrence rates of intraoperative and postoperative complications in both groups had no statistical significance (P >0.05). CONCLUSION: SSRAC is a new renal artery clamping technology, and its curative effect on LNSS patients is significant. In addition, SSRAC has high safety and little influence on renal functions.

ERK5­regulated RERG expression promotes cancer progression in prostatic carcinoma.

Big mitogen­activated protein kinase 1 [also named extracellular signal­regulated kinase (ERK) 5] is activated by mitogens and oncogenic signals and is strongly implicated in tumorigenesis. Our previous investigation indicated that ERK5 can induce prostatic carcinoma cell proliferation by promoting entry into the S phase of the cell cycle. In the present study, microarray and western blot analysis revealed that ERK5 can inhibit Ras­like oestrogen­regulated growth inhibitor (RERG) protein expression and that the inhibition of RERG expression promotes prostatic carcinoma cell proliferation and migration. In addition, pathological analysis indicated that the RERG expression level was associated with the malignancy of prostatic carcinoma. Furthermore, an apoptotic assay and western blot analysis demonstrated that the downregulation of RERG expression inhibits apoptosis by regulating the protein expression levels of B cell lymphoma­2 and c­Myc. Moreover, a luciferase activity assay indicated that the nuclear factor­κB pathway is associated with RERG­mediated apoptosis in prostatic carcinoma. Therefore, these data suggested that ERK5­regulated RERG expression plays a role in the progression of prostatic carcinoma, indicating that RERG may be a potential biomarker for the prognosis of patients with prostatic carcinoma.

Hollow PtPdRh Nanocubes with Enhanced Catalytic Activities for In Vivo Clearance of Radiation-Induced ROS via Surface-Mediated Bond Breaking.

Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H2 O2 via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.

The earlier, the better: the effects of different administration timepoints of sorafenib in suppressing the carcinogenesis of VEGF in rats.

PURPOSE: To investigate the optimal starting time point of sorafenib therapy in suppressing the tumor-promoting effects of VEGF up-regulation, which is frequently found after local therapy in clinical practice. METHODS: VEGF was intravenously injected to imitate the evaluated expression after local tumor therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly divided into four groups and sorafenib was administered at different timepoints: (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D) initiating sorafenib 72 h post-VEGF injection. The rate of tumor growth, median survival time, expression of VEGF, and microvessel density (MVD), as determined by immunohistochemical (IHC) examination, were compared. RESULTS: The results revealed that the tumor size and median survival time were significantly different between the three sorafenib groups compared to the control group (p < 0.05). Median survival times were 19.6 ± 1.78, 31.2 ± 6.99, 27.4 ± 4.9, and 26.5 ± 4.6 days in group A, B, C, and D, respectively. Furthermore, there was a difference in statistical significance between the two sorafenib groups B and D (p = 0.04). Tumors were collected for HE staining and IHC examination. The expression levels of VEGF in B, C, and D were 42.8 ± 7.96, 71.9 ± 15.73, and 73.6 ± 13.73, and all of them were significantly lower than that in the control group (88.3 ± 13.61). Furthermore, the level of MVD was 109.2 ± 8.98 in the control group, which was significantly higher than in the three sorafenib groups (45.7 ± 16.92, 77.1 ± 16.29, and 93.6 ± 12.87, all p < 0.05). CONCLUSIONS: According to our results, the most suitable regimen for the administration of sorafenib is before the increased expression of VEGF, which showed a potential advantage for controlling the tumor growth and prolonging the survival time of test animal via inhibiting VEGF-receptor expression through the bifunction of VEGF, and the reduction of tumor angiogenesis.