Single-Port Robot-Assisted Radical Prostatectomy with the Novel Shurui Single-Port Robotic Surgical System.

Purpose: The aim of this study was to explore the safety and efficacy of radical prostatectomy with a novel Shurui single-port (SR-SP) robotic surgical system. Methods: A total of 11 patients with prostate cancer were enrolled in this study. Extraperitoneal radical prostatectomy was performed using the SR-SP robotic surgical system for all patients. Clinicopathologic data, perioperative data, and short-term surgical outcomes were prospectively collected and analyzed. Results: Of the 11 patients, the median age was 65 years (range 52-73), and the median body mass index was 22.6 kg/m2 (range 20.2-26.7). The median operative time was 229 minutes (range 194-317), and the median console time was 167 minutes (range 141-265). The median blood loss was 40 mL (range 10-120), and none of the patients required intraoperative transfusion. There was no conversion to open surgery during the operation, and no assistant ports were added. The surgeons reported a good task load rating with a National Aeronautics and Space Administration Task Load Index (NASA-TLX) score of 25.1 ± 3.3 points. The median postoperative hospital stay time was 7 days (range 4-15). There were no severe intraoperative or postoperative complications (Clavien grade ≥3). Postoperative positive surgical margin occurred in 4 (36.4%) patients. No biochemical recurrence occurred within 1 month of surgery. The continence rate was 72.7% (8/11) 1 month after surgery. Conclusions: The new SR-SP robotic surgical system is safe, effective, flexible, and stable for application in radical prostatectomy.

Retroperitoneal Nephrometry Scoring System (RETRO) for Minimal-Invasive Partial Nephrectomy.

PURPOSE: To propose a standardized scoring system of renal tumors suitable for partial nephrectomy based on mini-invasiveness and retroperitoneal approach. MATERIALS AND METHODS: One-hundred and five patients in retroperitoneal group were prospectively enrolled from January 2017 to December 2018. Perioperative characteristics of all patients were collected: age, gender, BMI, preoperative blood test and imaging results, operation time (the time period starts from the skin incision to the final skin closure), estimated blood lost, clamping time, complications within 30 days, American Society of Anesthesiologists (ASA) score, pathology. An algorithm was extracted, and it was used to predict the risk of complications. RESULTS: Symptoms, ASA score and RETRO score were significantly correlated to postoperative complications, excluding tumor size, ischemia time and operation time. Adjusted RETRO points were an independent factor to predict complication rate (p = 0.006). Limitation was that it did not analyze the relationship between the RETRO score and the long-term outcomes. CONCLUSION: The RETRO score simplifies the risk evaluation of partial nephrectomy for patients with renal tumor, especially benefits those surgeries performed under robot-assisted laparoscope via retroperitoneal approach. The new RETRO score system that we developed is a selection criterion to perform surgery via different approaches, and an accurate system to evaluate the complexity during partial nephrectomy.

Preliminary Experience of Partial Nephrectomy Through a New Single-Port Surgical Robot System.

Purpose: To explore the preliminary safety and efficacy of the Shurui single-port (SP) surgical robot in partial nephrectomy (PN). Methods: This study prospectively enrolled patients with T1a renal tumors who met the inclusion criteria from February to July 2022 in The First Affiliated Hospital School of Medicine Zhejiang University. The operative outcomes and perioperative data, including clinical and histological data, were prospectively collected and analyzed. Results: A total of 13 patients were included in this study, including 7 males and 6 females. The median age was 53 (33-74) years, and the average body mass index was 24.9 ± 4.2 kg/m2. There were 6 cases of left kidney tumors and 7 cases of right kidney tumors in the 13 patients. The average tumor diameter was 1.9 ± 0.9 cm. In all operations, the diseased tissue was removed according to the established surgical plan. The average warm ischemia time was 26.2 ± 9.7 minutes; the average device docking time was 3.6 ± 1.8 minutes; and the average robotic arm operation time was 124.7 ± 40.4 minutes. All operations were successfully completed; there was no conversion to open surgery during the operation; and no operation holes were added. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) score was 26.3 ± 2.6 points, and no device-related adverse events occurred during the operation. The median time to discharge was 6 days (range, 4-11 days). Postoperative pathological examination showed that all tumor margins were negative. There were no Clavien grade ≥3 surgical complications in any of the patients during the perioperative period or at the 1-month postoperative follow-up. Conclusion: The new SP surgical robot system is safe, effective, flexible, and stable for application in PN.

Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS/ERK/JNK pathway.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a frequent complication of diabetes mellitus (DM), with limited therapy at present. This study aimed to explore the role and mechanism of Ganoderma lucidum polysaccharide (GLP) on DMED. Methods: DMED was induced in the experimental rats [male 12-week-old Sprague-Dawley (SD) rats] by treatment with streptozotocin (60 mg/kg) and apomorphine (APO). Next, rats in the GLP low dose (GLP-L)/GLP high dose (GLP-H) groups were treated with GLP (100 or 400 mg/kg/d, respectively) for 8 weeks. Subsequently, erectile function was assessed by APO and electrostimulation of the cavernous nerve (CN). Serum or penile testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cyclic guanosine monophosphate (cGMP) contents were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress indicators in the corpus cavernosum (CC) were measured by corresponding kits, and histological changes in the CC were observed by hematoxylin-eosin (HE) and Masson staining. Additionally, the apoptosis index, caspase-3, caspase-9, and eNOS expression, and mitochondrial membrane potential (MMP) were also detected. Furthermore, quantitative polymerase chain reaction (qPCR) and western blot assays were conducted to determine the NOS, TGF-ß1 mRNA expression, ERK1/2, eNOS, JNK phosphorylation, and arginase II protein expression. Results: The erectile function test revealed that erectile dysfunction (ED) was alleviated in the DMED rats following treatment with GLP. Moreover, GLP upregulated the T and cGMP content, improved the oxidative stress and histological injuries of CC, and also inhibited the apoptosis and MMP loss of penile tissues in DMED rats. Furthermore, GLP treatment enhanced the mRNA expression of NOS and TGF-ß1 and suppressed the phosphorylation of ERK1/2, eNOS, and JNK, as well as the protein expression of arginase II in DMED rats. Conclusions: GLP ameliorated DMED by repairing the CC pathological damage and upregulating NOS expression and ERK/JNK phosphorylation, indicating that GLP may be a candidate drug for DMED therapy.

Stem Cell Therapy for Thyroid Diseases: Progress and Challenges.

Background: Thyroid hormones are indispensable for organ development and maintaining homeostasis. Thyroid diseases, including thyroiditis and thyroid cancer, affect the normal secretion of hormones and result in thyroid dysfunction. Objective: This review focuses on therapeutic applications of stem cells for thyroid diseases. Methods: A literature search of Medline and PubMed was conducted (January 2000-July 2021) to identify recent reports on stem cell therapy for thyroid diseases. Results: Stem cells are partially developed cell types. They have the capacity to form specialized cells. Besides embryonic stem cells and mesenchymal stem cells, organ resident stem cells and cancer stem cells are recently reported to have important roles in forming organ specific cells and cancers. Stem cells, especially mesenchymal stem cells, have anti-inflammatory and anticancer functions as well. Conclusions: This review outlines the therapeutic potency of embryonic stem cells, mesenchymal stem cells, thyroid resident stem cells, and thyroid cancer stem cells in thyroid cells' regeneration, thyroid function modulation, thyroiditis suppression, and antithyroid cancers. Stem cells represent a promising form of treatment for thyroid disorders.

Association of Dietary Carrot Intake With Bladder Cancer Risk in a Prospective Cohort of 99,650 Individuals With 12.5 Years of Follow-Up.

Previous studies have provided limited evidence for the effect of carrot intake on bladder cancer incidence. This study aimed to evaluate the association between carrot consumption and bladder cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening cohort. PLCO enrolled 154,897 participants between November 1993 and July 2001 from 10 clinical screening centers throughout the United States. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model adjusting for confounders. A meta-analysis was also performed based on all available prospective studies with DerSimonian and Laird random-effects model to calculate summary relative risk (RR) and 95% CI. After a median of 12.5 years of follow-up, 762 incident bladder cancer cases occurred. We found no statistically significant association between dietary carrot intake and bladder cancer risk. The multivariate-adjusted HR of bladder cancer for participants in the highest category of total carrot intake compared with those in the lowest category was 0.96 (95% CI: 0.76-1.22; P for trend = 0.436). Corresponding adjusted HR was 0.98 (95% CI 0.90-1.06) per 1 SD increment of carrot intake. A meta-analysis based on two previous cohort studies and our study also found no significant association between carrot intake and bladder cancer risk (Summary HR 1.02, 95% CI 0.95-1.10) without obvious heterogeneity between studies (P = 0.859, I 2 = 0.0%). In summary, analysis of the PLCO cohort did not provide evidence that dietary consumption of carrot was associated with the risk of bladder cancer.

Identifying GNG4 might play an important role in colorectal cancer TMB.

BACKGROUND: Colorectal carcinoma (CRC) is one of the most leading cause of cancer death all over the world. The tumor immune microenvironment is illustrated to be necessary for the progress of CRC. And the accumulating evidence indicated that tumor mutation burden (TMB) is effective in differentiating responding population of immune checkpoint inhibitor (ICI) therapies in various cancers. In this study, we aimed to evaluated the potential relationship between TMB and the recurrence risk of CRC. METHODS: The transcriptomic and clinical data of CRC patients were collected from The Cancer Genome Atlas (TCGA) database (n= 382). Then the genomic analysis of tumor mutation burden and tumor purity were conducted by a computational method based on transcriptomic data. RESULTS: Firstly, we accessed the distribution of TMB and preferences at the gene and mutation level using somatic mutation data from TCGA data about CRC. We identified that high TMB predicted better prognosis of CRC patients. Secondly, the differentially expressed genes (DEGs) between the low TMB and high TMB group was clarified. Then the protein-protein interaction (PPI) analysis was performed, and the results confirmed ten hub genes among the DEGs. Utilizing the GEPIA web-tool, we discovered that GNG4 was up-regulated in tumor tissues, and GNG4 was related to the overall survival (OS) and tumor free survival (TFS) of CRC patients. Therefore, we considered GNG4 was essential for the tumor immune microenvironment of CRC. Furthermore, we also accessed the protein level of GNG4 in CRC and liver metastases from CRC. CONCLUSIONS: In this study, GNG4 was demonstrated to be the key element of the CRC TMB, which will be essential for the ICI therapy of CRC. Besides, GNG4 was up-regulated in CRC and liver metastases from CRC tissues. Thus, we thought that GNG4 might play an important role in colorectal cancer TMB and induce its metastasis in liver.

Seroprevalence of AIH-related autoantibodies in patients with acute hepatitis E viral infection: a prospective case-control study in China.

The seroprevalenc of autoimmune hepatitis (AIH)-related antibodies in patients, particularly Asians, with acute hepatitis E (AHE) is unclear. In this study, we investigated whether acute hepatitis E virus (HEV) infection is associated with the seroprevalence of AIH-related autoantibodies and assessed their impact on the disease characteristics. AIH-related autoantibodies were detected by indirect immunofluorescence in 198 AHE patients and 50 type 1 AIH patients. The positivity rates of against nuclear antigen (ANA) and smooth muscles antibody (SMA) in AHE patients were 37.4% and 22.7%, and the total positivity rate was 50%. Compared to those in AIH patients, the positivity rates of ANA-H and SMA-AA were significantly lower (35.1% vs. 82.1% and 4.4% vs. 88.4%). Female gender and the ALT level, but not immunosuppressive or antiviral drugs, were independently predictive of the presence of AIH-related autoantibodies in AHE patients. Fifty-two patients positive for AIH-related autoantibodies were followed up for 12 months. During this period, 33 of them became negative and 19 remained positive, albeit with significantly decreased titres. In conclusions, the seroprevalence of AIH-related autoantibodies in AHE patients was elevated, particularly in females, but their subspecificities and titres differed from those of type 1 AIH. Acute HEV infection may be related to AIH.Abbreviations: AIH: autoimmune hepatitis; AHE: acute hepatitis E; ANA: against nuclear antigen; SMA: smooth muscles antibody; ANA-H: ANA with homogeneous pattern; SMA-AA: SMA with anti-actin pattern; Anti-LKM1: anti- liver-kidney microsomes-1 antibody; ANCA: anti-neutrophil cytoplasmic antibody; AMA: anti-mitochondrial antibody; Anti-SLA: anti-soluble liver antigen; Anti-LC1: anti-liver cytoplasmic type 1 antibody; pANCA: perinuclear antineutrophil cytoplasmic antibody.

Robot-Assisted Laparoscopic Excision of Complicated Retroperitoneal Tumors with Four Arms Via Retroperitoneal Way: A Unique Minimal-Invasive Approach.

Background: Surgical management of complicated retroperitoneal mass is one of the most challenging urologic oncologic surgeries. This study aims to describe our technique and experience in dealing with retroperitoneal mass. Methods: Three patients with complicated retroperitoneal mass were treated with robot-assisted surgery with four arms through retroperitoneal approach. Surgical Procedure: Our standardized anatomic-based "kidney safe first, then mass resection" technique for robot-assisted complicated retroperitoneal mass resection focused on minimizing the chance of renal pedicle injury. Baseline demographics, pathology data, and latest follow-up outcome were obtained. Results: In this retrospectively reviewed case series, all 3 patients were successfully treated with robot-assisted surgery with four arms during retroperitoneal space. One patient received paravertebral mass resection 2 weeks after the robotic surgery. Mean data included operative time of 175 minutes, estimated blood loss was 133 mL, and hospital stay was 4 days. No complications occurred. Conclusions: Robot-assist surgery for complicated retroperitoneal mass with four arms is a safe and feasible way. Patient Summary: Mini-invasive treatment for retroperitoneal mass with robotic four arms through retroperitoneal approach is a feasible way. The approach reduces interruption of intracorporeal structure and organs. And patients could benefit from the retroperitoneal approach with a quicker recovery.

Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population-based study of 16,643 patients.

BACKGROUND: Bone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra-skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses. METHODS: In total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed. RESULTS: Lung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone-only metastases showed the longest mean survival time (35.87 months, p < 0.001), followed by patients with bone and lung metastases (30.74 months, p < 0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p < 0.001). Age > 70 years, unmarried status, high tumor grade, prostate-specific antigen (PSA) > 50 ng/ml, and Gleason score ≥ 8 were associated with poor OS (all p < 0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p < 0.01). Chemotherapy improved OS in patients without brain metastases (all p < 0.05). For patients with bone-only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231-0.495; p < 0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388-0.829; p = 0.003), and chemotherapy (HR, 0.850; 95% CI 0.781-0.924; p < 0.001) were associated with prolonged OS. CONCLUSIONS: Age, race, tumor grade, PSA, Gleason score, sites of synchronous extra-skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone-only metastases. Further investigation is warranted to validate these findings.

ACADS acts as a potential methylation biomarker associated with the proliferation and metastasis of hepatocellular carcinomas.

BACKGROUND: Hepatocellular carcinomas (HCC) constantly rank among the malignancies with the highest death tolls on the global scale. Moreover, HCC are associated with a limited set of therapeutic options. This is particularly true in the case of advanced stage cancers, where long-term survival is uncommon. For the inoperable, advanced HCC patients, chemotherapy is the main modality of treatment. Due to the lack of known molecular targets, the efficacy of the chemotherapy is limited. CONCLUSION: These findings clearly indicate that DNA methylation plays a key role in regulating ACADS expression and that it can be a potential therapeutic target for treating HCC. MATERIALS AND METHODS: A thorough comparative analysis of 282 cancer samples with 47 normal samples from GEO datasets resulted in the observation that that the level of ACADS was significantly downregulated in HCC. Loss-of-function analyses were then conducted to understand the biological function of ACADS in HCC. It was noted that ACADS was involved in the proliferation and metastasis of HCC. Experiments involving the knockdown of DMNT expression led to the discovery that the expression of ACADS in the HCC cells was significantly increased. The TCGA database was then employed to identify tumor tissue samples which showed higher methylation levels at cg01535453, cg08618068, and cg10174836 (which are the target sites of the ACADS CpG islands) as compared with normal liver tissue samples. All these findings indicated that ACADS might be a novel methylation biomarker associated with HCC.

Retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy in adult patients with duplex kidneys.

Background: To report our experience with retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy in adult patients with duplex kidneys. Methods: We retrospectively reviewed the medical records of 7 patients who underwent retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy at our institution between September 2014 and July 2017. Of the robot-assisted laparoscopic procedures, 5 were on the left and 2 on the right side. Results: All patients underwent robot-assisted laparoscopic surgery successfully in a totally retroperitoneal manner without conversion to open surgery. The mean operative time was 175 mins (range 140-270). The mean estimated blood loss was 84 mL (range 20-200). The mean postoperative hospital stay was 7 days (range 5-9). No major intraoperative and postoperative complications occurred. All patients had a resolution of their presenting symptoms after surgery at a mean follow-up of 24 months (range 14-38). Conclusion: Our initial clinical experience suggests that robot-assisted laparoscopic upper pole heminephrectomy using a retroperitoneal approach for a duplex kidney appears to be safe with acceptable perioperative outcomes.

Mucinous Prostate Cancer Shows Similar Prognosis to Typical Prostate Acinar Carcinoma: A Large Population-Based and Propensity Score-Matched Study.

Background: Mucinous prostate cancer (PCa) is an extremely rare form of prostate malignancy. To date, the limited knowledge of its biology and outcomes stems from mostly small, single institution experiences. We analyzed the Surveillance, Epidemiology, and End Results (SEER) database to explore the incidence and treatment of mucinous PCa together with its prognostic factors to gain relatively large and consolidated insights. Methods: Age-adjusted incidence (AAI) rates were evaluated over time. Propensity score matching (PSM) and Kaplan-Meier analyses were used to compare the prognosis between mucinous PCa and typical prostate acinar adenocarcinoma. We assessed cancer-specific survival (CSS) and overall survival (OS) after patient stratification according to summary stage and treatment choice. Cox hazards regression analysis was performed to determine independent predictors of CSS and OS. Results: The AAI in 2016 was 0.24 per million. Patients with mucinous PCa had similar CSS and OS to matched individuals with typical prostate acinar adenocarcinoma. In terms of treatment, 65.3% of mucinous PCa patients underwent surgery, and 23.9% received radiation therapy. Patients who underwent surgery had longer survival (CSS, p = 0.012; OS, p < 0.001), and patients who received radiation therapy had similar survival to those who did not receive radiation therapy (CSS, p = 0.794; OS, p = 0.097). A multivariate Cox analysis for CSS and OS showed that older age (CSS: HR: 4.982, p = 0.001; OS: HR: 4.258, p < 0.001) and distant stage (CSS: HR: 40.224, p < 0.001; OS: HR: 9.866, p < 0.001) were independent prognostic factors for mucinous PCa patients. Conclusions: Mucinous PCa has an extremely low AAI. Analysis of its outcomes indicates that it is not a more malignant tumor as previously suspected. Mucinous PCa shows a similar prognosis to typical prostate acinar carcinoma. Surgery was associated with prolonged survival. An older age at diagnosis and distant stage was associated with poor survival.

Robotic-assisted Urethra-sparing Simple Prostatectomy Via an Extraperitoneal Approach.

OBJECTIVE: To present an original technique of robotic-assisted urethra-sparing simple prostatectomy (RAUSP) for treating patients with benign prostatic hyperplasia. MATERIALS AND METHODS: From April 2015 to December 2016, 27 patients underwent RAUSP via an extraperitoneal approach. Baseline patient characteristics, perioperative outcomes, pathologic outcomes, postoperative Clavien complications, International Prostate Symptom Score, International Index of Erectile Function, and ejaculatory function were assessed. RESULTS: Twenty-six patients (96.3%) successfully underwent RAUSP, one patient (3.7%) was converted to simple prostatectomy. Median operative time was 169 minutes (interquartile range: 150-185); median estimated blood loss was 235 mL (interquartile range: 180-300). Seven cases (26.9%) required urethral repair secondary to inadvertent urethrotomy. Mean catheterization time was 1.6 days (range 1-5). Clavien complications were reported, 6 being low grade (grade 1 or 2) with a single 3a complication (gross hematuria requiring bladder irrigation). Mean follow-up duration was 16.4 months (range 9-30). Postoperative questionnaire demonstrated that international prostate symptom score (P < .001) and quality of life score (P < .001) were significantly improved postoperatively. A total of 14 patients reported erectile function, 13 of which had normal ejaculation, only 1 complained retrograde ejaculation. CONCLUSION: RAUSP is technically feasible for patients with benign prostatic hyperplasia. Our data indicate that patients have short catheterization time, an acceptable risk profile, significant improvements of voiding function and maintaining antegrade ejaculation following this urethral-sparing technique.

Downregulation of HDAC6 promotes angiogenesis in hepatocellular carcinoma cells and predicts poor prognosis in liver transplantation patients.

HDAC6, a member of histone deacetylation family, is reported to play critical roles in transcription regulation, cell cycle progression, and cancer development. However, the expression status and significance of HDAC6 in hepatocellular carcinoma (HCC) is still controversial, and little is known about the role of HDAC6 in HCC angiogenesis and the correlation between expression of HDAC6 and prognosis of HCC patients with liver transplantation (LT). Our experiments showed HDAC6 was significantly downregulated in HCC tissues (P = 0.025), and low expression of HDAC6 was found to be closely associated with recurrence (P = 0.006), and could predict poor recurrence-free survival (P = 0.047) for HCC patients with LT. Moreover, knockdown of HDAC6 could promote HUVEC migration, proliferation, and tube formation in vitro, and suppress HCC cell apoptosis, and promote HCC cell proliferation in hypoxia. Remarkably, knockdown of HDAC6 could significantly up-regulate the expression of HIF-1α and VEGFA in vivo and in vitro, which facilitated HIF-1α mediated angiogenesis in HCC. Further study showed that HDAC6 was down-regulated under hypoxia in a time dependent manner. Hence, the present findings suggested a role for suppression of HDAC6 in promoting the angiogenesis in HCC by HIF-1α/VEGFA axis. HDAC6 may serve as a recurrence predictive factor for HCC after LT and pharmacological or genetic activation of HDAC6 could be a novel anti-angiogenesis approach for HCC therapy.

Hsp27 Acts as a Master Molecular Chaperone and Plays an Essential Role in Hepatocellular Carcinoma Progression.

AIMS: Hsp27, a master molecular chaperone, plays an important role in cancer. However, the specific co-chaperones that partner with Hsp27 and the role of Hsp27 in hepatocellular carcinoma (HCC) are not fully enumerated. The present study focuses on the role of Hsp27 in HCC and explores its potential co-chaperones in HCC development. METHODS: Gene overexpression or knockdown was used to observe the role of Hsp27 in HCC. Co-immunoprecipitation and mass spectrometry were used to explore apoptosis resistance by regulating multiple co-chaperones of Hsp27. Hsp27 protein-protein interaction (PPI) networks were constructed by the MetaCore software. RESULTS: Hsp27 was upregulated in HCC tissues, and Hsp27 overexpression significantly facilitated formation of HCC cell colony and invasion in normoxia and tolerance in hypoxia by interacting with HIF-1α. Next, the analysis of microarrays revealed that Hsp27 regulated several cellular signaling pathways, including Wnt, ErbB and TGF-ß signaling. Moreover, we characterized the Hsp27 PPI map, which indicated that Hsp27 along with its co-chaperones formed different complexes and exerts transcription regulation activity by activating sp1, c-Myc, p53 and ESR1. CONCLUSIONS: Hsp27 along with its co-chaperones was related to the development of HCC by regulating multiple signaling pathways, and drugs that target Hsp27 along with its co-chaperones may be a potential therapy for HCC.

Human heat shock protein 27 exacerbates ischemia reperfusion injury in rats by reducing the number of T regulatory cells.

Ischemia reperfusion injury (IRI) occurs in almost every liver surgery and is associated with the reduction of the liver blood flow. Ischemia impairs liver function and can even cause liver failure following surgery. The present study aimed to identify a new molecular target allowing the reduction of IRI and explore the related cellular mechanism. Adenovirus (~2.5x10(12) viral particles) bearing the human heat shock protein 27 (HSP27) gene was injected into rat liver through the ileocecal vein. Five days following the injection, ischemia was induced by clamping the median and left portal veins, hepatic arteries and bile ducts. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and superoxide dismutase (SOD) were measured. The infiltration of inflammatory cells and the expression of pro-inflammatory factors were investigated. The number of regulatory T cells (Tregs) was measured by flow cytometry. At 2 h following reperfusion, the group injected with HSP27 had the highest level of ALT and AST, followed by the group injected with HSP27 and treated with gadolinium trichloride (GdCl3), the empty vector-injected and the vector+GdCl3 groups. The HSP27 group also had the lowest levels of the oxidative stress-protective factors SOD and GSH, and the highest levels of pro-inflammatory factors. The number of Tregs was reduced in the groups injected with HSP27. In conclusion, the human HSP27 protein can effectively accelerate liver damage at the early stages of IRI in rats. Tregs might play a critical role in HSP27­induced liver injury.

Prohibitin-2 promotes hepatocellular carcinoma malignancy progression in hypoxia based on a label-free quantitative proteomics strategy.

The rapid growth of hepatocellular carcinoma (HCC) leading to tumor hypoxia is a common pathological phenomenon. Meanwhile, tumor hypoxia can promote a change in the biological properties of tumor cells. It may enhance the survival of tumor cells under stress conditions, resulting in resistance to apoptosis and angiogenesis. The moleculars that could modulate the malignant phenotypes of HCC cells remain largely unknown. Based on label-free quantitative proteomic data, we found a significant upregulation of prohibitin-2 (PHB2) in HCC tissues. Treatment of hepatoma cells with small interfering RNAs against PHB2 suppressed cell growth and colony formation, led to G1 phase arrest and sensitized HCC cells to apoptosis. Moreover, inhibition of PHB2 expression dramatically repressed the ability of HCC cells to adapt to hypoxic microenvironments and resist chemotherapy-induced apoptosis. Thus, PHB2 in HCC supports the development and progression of hepatocellular malignancy to hypoxia, and implicates the potential antagonist function of PHB2 in transarterial chemoembolization treatment.

Interleukin-35: the future of hyperimmune-related diseases?

Interleukin (IL-35) is a newly identified heterodimeric cytokine belonging to the IL-12 family. It contains Epstein-Barr virus-induced gene 3 subunit and IL-27 p35 subunit. Although its receptor and signaling pathway are not clear, we presumed that its receptor is composed by two chains that might be similar to those receptors of IL-12, IL-23, and IL-27. We also believe that the signal transducer activator of transcription family members is involved in its signaling pathway. It was reported that IL-35 could suppress Teff cell proliferation and Th17 development. It was considered to have a potential therapeutic effect against immune diseases. In our perspective, the finding of IL-35 is of great significance, since it can regulate T cells, which is an important therapeutic target of immunological disorders. IL-35 would promote the development of different kinds of vaccines, even vaccine for special cancer, and be promising to cure autoimmune and inflammatory diseases.

Recipient outcomes of salvage liver transplantation versus primary liver transplantation: a systematic review and meta-analysis.

Salvage liver transplantation (SLT), or liver transplantation after liver resection (LR), has been performed after primary LR for many years. However, the true outcomes and risks of SLT versus primary liver transplantation (PLT) remain unclear. We performed a systematic review and meta-analysis to evaluate the survival rate of SLT recipients and the incidence of postoperative complications. Among 2799 screened references, 7 eligible studies were identified. The results of the meta-analysis indicated no statistically significant differences in the overall survival rates of SLT and PLT: the pooled relative risk (RR) was 0.99 [95% confidence interval (CI) = 0.90-1.09, P = 0.87] at 1 year, 0.97 (95% CI = 0.83-1.13, P = 0.68) at 3 years, and 0.96 (95% CI = 0.81-1.13, P = 0.61) at 5 years. As for postoperative complications, there were no statistically significant differences in the incidence of sepsis and biliary complications between SLT and PLT, but there was a significantly higher incidence of bleeding with SLT (RR = 2.84, 95% CI = 1.57-5.13, P = 0.001). In conclusion, the overall survival associated with SLT is similar to that associated with PLT. Because of the limited organ donor pool, SLT might be an acceptable therapy for patients undergoing primary LR for hepatocellular carcinoma.