cGAS suppresses ß-cell proliferation by a STING-independent but CEBPß-dependent mechanism.

AIMS/HYPOTHESIS: cGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in ß-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on ß-cell proliferation, particularly in the context of diabetes. METHODS: Utilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in ß-cell function. This involved ß-cell-specific cGAS knockout (cGASßKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. RESULTS: cGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and ß-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting ß-cell mass. Interestingly, STING knockout did not affect pancreatic ß-cell mass, suggesting a STING-independent mechanism for cGAS's role in ß-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPß, a known suppressor of ß-cell proliferation, concurrently with increased ß-cell proliferation. Moreover, overexpression of CEBPß reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating ß-cell proliferation. These results confirm that cGAS regulation of ß-cell proliferation via a CEBPß-dependent but STING-independent mechanism. CONCLUSIONS/INTERPRETATION: Our findings highlight the pivotal role of cGAS in promoting ß-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPß expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling ß-cell mass and identifies a potential therapeutic target for enhancing ß-cell proliferation in the treatment of diabetes.

Circulating Galectin-3 levels and Diabetic Nephropathy: a systematic review and meta-analysis.

AIMS: Changes of serum galectin-3 (Gal-3) is associated with the pathogenesis of diabetic nephropathy (DN). However, current literature indicates that the given results remain debatable and inconsistent. Hence, the aim of this present meta-analysis was to focus on the predictive role of serum Gal-3 in patients with DN. METHODS: The PubMed, Embase, Cochrane Library and Web of Science databases were systematically searched for studies that reported the relationship between Gal-3 levels and DN risk, from the inception of each database to March, 2023. The literature we selected for inclusion based on inclusion and exclusion criteria. The standard mean difference (SMD) with corresponding 95% confidence intervals (95% CI) were used to investigate the association. When I2 value exceeding 50%, we will consider it has the presence of a higher level of heterogeneity. A sensitivity analysis and subgroup analysis were performed to seek the potential sources of heterogeneity. The quality assessment was performed using according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The data analysis was conducted using STATA version 13.0 software. RESULTS: We ultimately enrolled 9 studies enrolling a total of 3137 patients in the final analysis. The SMD of serum Gal-3 was higher in patients with DN group (SMD 1.10 ng/mL [0.63, 1.57]; I2: 96.1%). Upon removal of a study in sensitivity analysis, patients with DN had higher serum Gal-3 levels compared to control patients (SMD 1.03 ng/mL [0.52, 1.54], I2: 94.4%). Further subgroup analysis was performed based on the region. No matter in Asia, Europe or Africa, the serum Gal-3 level of DN patients is significantly higher than that of the control population (SMD: 0.73; 95% CI: 0.58 to 0.87 for Asian; SMD: 0.79; 95% CI: 0.48 to 1.10 for Europe; SMD: 3.15; 95% CI: 2.73 to 3.56 for Africa). CONCLUSION: In conclusion, these results suggested that higher serum Gal-3 may increase the risk of DN. More fundamental studies are necessary to clarify the exact physiopathological basis mechanisms of Gal-3 effects. In addition, further research, especially emphasis on the cut-off value should be given, and is best to predict their actual importance as well as the diagnostic accuracy.

Excellent clinical outcomes of renal transplant from pediatric deceased donors with acute kidney injury.

BACKGROUND: The use of kidneys from deceased donors with acute kidney injury (AKI) to expand the donor pool is an ongoing trend. Prior research on the utilization of AKI donor kidneys, especially from pediatric AKI donors, was limited and has been subject to small sample sizes. In this study, we aimed to evaluate the safety and effectiveness of early post-transplantation outcomes in pediatric deceased donors with AKI. METHODS: This retrospective study compared the clinical results (including delayed graft function [DGF], acute rejection, patient and death-censored graft survival rates and renal function post-transplant) of kidney transplantation from deceased donors who were categorized as pediatric donors and adult donors with or without AKI, as defined by the Kidney Disease: Improving Global Outcomes (KIDGO) criteria, at our center between January 2018 and December 2020. RESULTS: Of the 740 patients, 154 received kidneys from pediatric donors (with AKI group [n = 41]; without AKI group [n = 113]), and 586 received kidneys from adult donors (with AKI group [n = 218]; without AKI group [n = 368]). The baseline characteristics were similar in both cohorts. No significant difference was observed in 1-year patient survival, death-censored graft survival, or acute rejection between the AKI and non-AKI groups in both the pediatric and adult cohorts. However, compared with those transplanted with adult AKI kidneys, those transplanted with pediatric AKI kidneys showed a superior recovery of allograft function. In pediatric cohorts, no significant difference was found in serum creatinine/estimated glomerular filtration rate (SCr/eGFR) between the AKI and non-AKI groups, even in the first week post-transplant. In contrast, the post-transplant SCr/eGFR level of the AKI group recipients in adult cohorts did not recover to a level statistically similar to that of non-AKI recipients, even at 6-months post-transplant. Nonetheless, AKI kidney recipients were at an increased risk of DGF in both pediatric (34.1% vs. 16.8%) and adult (38.5% vs. 17.4%) cohorts. CONCLUSIONS: Kidney transplantation from deceased donors with AKI has short-term clinical outcomes comparable to those of non-AKI kidney transplantation. Pediatric AKI kidneys have a superior recovery of allograft function. The transplant community should utilize this donor pool to minimize waiting-list-related mortalities.

Fibroblast growth factor 21 may be a strong biomarker for renal outcomes: a meta-analysis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases. METHODS: The outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger's and Begg's tests was performed to estimate the publication bias that existed in the study. RESULTS: A total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70-1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39-0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72-3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31-2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients. CONCLUSION: Serum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding.

The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from ß cells.

Pancreatic ß cell failure is a hallmark of diabetes. However, the causes of ß cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue-enriched secretory molecule, as a negative regulator of insulin secretion in ß cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet-fed mice. Mechanistically, TN binds with high selectivity to ß cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-ß cell cross-talk that contributes to ß cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

Utilization of HCV Viremic Kidneys with Genotyping/Subtyping-Free Sofosbuvir/Velpatasvir Treatment Strategy: Experience from China.

Background: Owing to the advent of pangenotypic direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) treatment, utilization of HCV-infected deceased donor kidneys with simplified genotyping/subtyping-free sofosbuvir/velpatasvir (SOF/VEL) treatment strategy is now becoming a promising strategy for expanding the organ donor pool. Methods: This retrospective, comparative, single-center study included HCV viremic donor kidneys that were transplanted to 9 HCV-positive (HCV Ab-positive) recipients (D+/R+ group) and 14 HCV-negative recipients (D+/R- group) from May 2018 to January 2021. Both groups received prophylaxis with SOF/VEL treatment within 1-week posttransplant devoid of HCV genotyping/subtyping. The primary outcomes were sustained virologic response 12 weeks after completion of therapy (SVR12) and graft survival at 1-year posttransplant. Results: Baseline characteristics were similar between the HCV D+/R- and D+/R+ groups. The mean age of all recipients was 39.09 ± 9.65 (SD) years, and 73.9% were male. A total of 92.9% (13 out of 14) recipients had pretreatment HCV viremia in the D+/R- group. The pretreatment HCV viral load in the D+/R+ group (5.98, log 10 IU/mL; IQR, 5.28-6.53) was significantly higher than that in the D+/R- group (3.61, log 10 IU/mL; IQR, 2.57-4.57). After SOF/VEL treatment, SVR12 was achieved in all recipients, with a 100% 1-year patient and graft survival rates. The D+/R+ group had a higher incidence of abnormal liver function (44.4% vs. 7.1%). No significant difference was observed between the two groups in terms of DGF, acute rejection, ALT, serum creatinine, and eGFR within 1-year posttransplant. No severe adverse events associated with either HCV viremia or SOF/VEL were observed. Conclusions: Using a simplified genotyping/subtyping-free SOF/VEL treatment strategy, kidneys from hepatitis C viremic donors for both infected and uninfected recipients presented with safe, excellent, and comparable 1-year outcomes, which can safely expand the donor pool. HCV-positive donor kidneys should be utilized regularly, regardless of the recipient's HCV status.

GRB10 regulates ß-cell mass by inhibiting ß-cell proliferation and stimulating ß-cell dedifferentiation.

Decreased functional ß-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10 (GRB10), a negative regulator of insulin and mTORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. ß-cell-specific knockout of Grb10 in mice increased ß-cell mass and improved ß-cell function. Grb10-deficient ß-cells exhibit enhanced mTORC1 signaling and reduced ß-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced ß-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of ß-cell dedifferentiation and ß-cell mass, which exerts its effect by inhibiting mTORC1 signaling.

Comparison of Outcomes of Kidney Transplantation From Extremely Low Body Weight ≤5kg Versus Larger Body Weight Pediatric Donors.

Background: Kidney transplantation from donors who weigh ≤5 kg is performed at only a few transplant centers owing to the high complication and low graft survival rates associated with this approach. Methods: We retrospectively compared the results of kidney transplantation at our center between January 2015 and December 2019 based on the following pediatric donor criteria: donor body weight ≤5 kg (n=32), 5 kg< donor weight ≤20 kg (n=143), and donor weight >20 kg (n=110). We also perform subgroup analysis of kidney transplantation outcomes from ≤5 kg donors, using conventional (dual separate and classic en-bloc KTx)/novel (en-bloc KTx with outflow tract) surgical methods and allocating to adult/pediatric recipients. Results: The death-censored graft survival rates from extremely low body weight ≤5kg at 1 month, and 1, 3, and 5 years were 90.6%, 80.9%, 77.5%, and 73.9%, respectively, which were significantly lower than that from larger body weight pediatric donors. However, the 3-, and 5-year post-transplantation eGFRs were not significantly different between the pediatric and adult recipient group. The thrombosis (18.8%) and urinary leakage (18.8%) rates were significantly higher in the donor weight ≤5 kg group. Compared with 5 kg< donor weight ≤20 kg group, donor weight ≤5kg group was at elevated risk of graft loss due to thrombosis (OR: 13.4) and acute rejection (OR: 6.7). No significant difference on the outcomes of extremely low body weight donor kidney transplantation was observed between adults and pediatric recipients. Urinary leakage rate is significantly lower in the novel operation (8.7%) than in the conventional operation group (44.4%). Conclusions: Although the outcomes of donor body weight ≤5kg kidney transplantation is inferior to that from donors with large body weight, it can be improved through technical improvement. Donors with body weight ≤5 kg can be considered as an useful source to expand the donor pool.

Rheb1 promotes glucose-stimulated insulin secretion in human and mouse ß-cells by upregulating GLUT expression.

Reduced ß-cell mass and impaired ß-cell function are primary causes of all types of diabetes. However, the intrinsic molecular mechanism that regulates ß-cell growth and function remains elusive. Here, we demonstrate that the small GTPase Rheb1 is a critical regulator of glucose-stimulated insulin secretion (GSIS) in ß-cells. Rheb1 was highly expressed in mouse and human islets. In addition, ß-cell-specific knockout of Rheb1 reduced the ß-cell size and mass by suppressing ß-cell proliferation and increasing ß-cell apoptosis. However, tamoxifen-induced deletion of Rheb1 in ß-cells had no significant effect on ß-cell mass and size but significantly impaired GSIS. Rheb1 facilitates GSIS in human or mouse islets by upregulating GLUT1 or GLUT2 expression, respectively, in a mTORC1 signaling pathway-dependent manner. Our findings reveal a critical role of Rheb1 in regulating GSIS in ß-cells and identified a new target for the therapeutic treatment of diabetes mellitus.

miR-181a Upregulation Promotes Radioresistance of Nasopharyngeal Carcinoma by Targeting RKIP.

BACKGROUND: Radioresistance is the leading cause of treatment failure for nasopharyngeal carcinoma (NPC). Therefore, screening the critical regulators in radioresistance and revealing the underlying mechanisms is imperative for improvement of therapeutical efficacy in NPC. MATERIALS AND METHODS: Our previous study has proved that miR-181a may serve as a pro-radioresistant miRNA. In this study, we explored the expression of miR-181a in NPC, especially in radioresistant NPC samples, by qPCR. Moreover, the clinical significance of miR-181a level was also analyzed. Furthermore, the functions of miR-181a, both in vitro and in vivo, were detected via a serial of assays such as CCK-8, plate clone survival, apoptosis, and xenograft tumor model. The downstream target of miR-181a was also validated by dual luciferase reporter assay and the roles of miR-181a's target in the regulation of NPC radioresistance were investigated. RESULTS: The results revealed that miR-181a was significantly upregulated in NPC, especially in radioresistant NPC. MiR-181a level is positively correlated to lymph node metastasis and advanced TNM stages and negatively associated with overall survival rate in NPC. Ectopic expression of miR-181a in radiosensitive NPC cells, or overexpression of miR-181a inhibitor in radioresistant NPC cells, could enhance or impair the radioresistance of NPC cells supported by the results from both in vitro and in vivo, respectively. Mechanistically, dual luciferase report assay indicated that miR-181a could directly target RKIP. Moreover, both in vitro and in vivo experimental outcomes indicated that RKIP restoration and knockdown could antagonize the effects of miR-181a and miR-181a inhibitor in the regulation of NPC radioresistance. CONCLUSION: Collectively, the findings of this study proved that miR-181a is upregulated and promotes radioresistance by targeting RKIP in NPC. Targeting miR-181a/RKIP axis may be a valid path for reinforcing radiosensitivity and eventually improving the outcomes of clinical treatment in NPC.

ATG3, a Target of miR-431-5p, Promotes Proliferation and Invasion of Colon Cancer via Promoting Autophagy.

BACKGROUND: Studies have indicated that ATG3 could mediate the effects of other tumor-related regulators in carcinogenesis. However, the expression, role, and mechanism of ATG3 itself in cancers are rarely revealed. Thus, we explored the expression, function, and mechanism of ATG3 in colon cancer. MATERIALS AND METHODS: The expression of ATG3 was detected in colon cancer tissues and cell lines, as well as in adjacent tumor tissues and normal colon epithelial cells. The effects of ATG3 alteration on proliferation and invasion were further analyzed. The expression and role of miR-431-5p, a potential negative regulator of ATG3, were also studied. Eventually, the role of autophagy in ATG3 related effects in colon cancer was checked. RESULTS: ATG3 is upregulated in colon cancer tissues and cells demonstrated by qPCR and IHC. ATG3 knockdown significantly suppressed proliferation and invasion of colon cancer cells indicated by plate clone formation and Transwell invasion assays. The expression of miR-431-5p is downregulated and negatively correlates with ATG3 in colon cancer. Furthermore, luciferase report system, plate clone formation and Transwell invasion assays demonstrated that miR-431-5p could prohibit cell proliferation and invasion via directly targeting ATG3 in colon cancer. Eventually, Western blot, plate clone formation and Transwell invasion assays proved that autophagy block could antagonize the promotive functions of ATG3 on proliferation and invasion in cancer suggesting autophagy activation accounts for the promotive role of ATG3 on proliferation and invasion in colon cancer. CONCLUSION: Collectively, ATG3 upregulation, caused by downregulated miR-435-5p, promotes proliferation and invasion via an autophagy-dependent manner in colon cancer suggesting that miR-431-5p/ATG3/autophagy may be a potential therapeutic target in colon cancer.

CAV3.1 knockdown suppresses cell proliferation, migration and invasion of prostate cancer cells by inhibiting AKT.

BACKGROUND: Aberrant expression of CAV3.1, one of T-type Ca2+ channels, is reported to exert important functions in pathological processes, including carcinogenesis. However, its expression pattern and function in prostate cancer (PCa) remains unclear. MATERIALS AND METHODS: The expression pattern of CAV3.1 was analyzed in multiple ways, including online analysis in Oncomine database, experimental analyses in cell lines, and collected clinical specimens using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and Western blot. Then, CAV3.1 was downregulated in PCa cells to explore its functions. RESULTS: Upregulated CAV3.1 in PCa tissues and cells was confirmed by analyzing mRNA expression datasets from Oncomine and quantitative reverse transcription polymerase chain reaction detection, respectively. Accordingly, significantly higher CAV3.1 protein level in PCa tissues specimens than that in benign prostatic hyperplasia tissues was indicated by immunohistochemical staining. In addition, CAV3.1 upregulation was positively associated with metastasis. Depletion of CAV3.1 impaired the proliferation, migration, and invasion ability of PCa cells demonstrating by cell functional experiments, such as CCK-8, cell cycle distribution, plate clone formation, scratch wound healing, and transwell invasion assays. Mechanistically, due to constrained Akt activity, CAV3.1 knockdown resulted in decreased level of CCND1, N-cadherin, and Vimentin, and increased level of E-cadherin whose expressions could be reversed by ectopic Akt expression. Similarly, ectopic Akt expression also rescued the inhibitory effects of CAV3.1 knockdown on cell functions like proliferation and migration in PCa cells. CONCLUSION: Upregulated CAV3.1 is positively associated with the development of PCa. CAV3.1 knockdown can inhibit PCa cell proliferation, migration, and invasion by suppressing AKT activity.

[Phloroglucinol combined with parecoxib for cystospasm after transurethral resection of the prostate].

Objective: To evaluate the effect and safety of phloroglucinol combined with parecoxib on cystospasm after transurethral resection of the prostate (TURP). METHODS: We conducted a prospective randomized case-control study on 98 patients treated by TURP. After operation, the patients were randomly assigned to a treatment (n=50) and a control group (n=48), the former treated by intravenous injection of 80 mg phloroglucinol qd plus 40 mg parecoxib bid while the latter given 80 mg phloroglucinol only, both for 3 successive days. Then we recorded the frequency and duration of cystospasm, visual analogue scales (VAS), adverse reactions, post-operative bladder irrigation time, catheter-indwelling time, and hospital stay and compared them between the two groups of patients. RESULTS: Compared with the controls, the patients in the treatment group showed a significantly lower frequency of cystospasm (ï¼»1.95±0.14ï¼½ vs ï¼»0.70±0.65ï¼½ times, P<0.01), duration of cystospasm (ï¼»0.44±0.21ï¼½ vs ï¼»0.12±0.14ï¼½ min, P<0.01), and VAS score (2.70±1.80 vs 1.90±1.30, P<0.01) at 48－72 hours after TURP, but no statistically significant differences were found between the control and treatment groups in the post-operative bladder irrigation time (ï¼»2.75±0.87ï¼½ vs ï¼»2.64±0.83ï¼½ d, P>0.05), catheter-indwelling time (ï¼»3.52±0.32ï¼½ vs ï¼»3.44±0.42ï¼½ d, P>0.05), and hospital stay (ï¼»5.23±0.81ï¼½ vs ï¼»5.10±0.73ï¼½ d, P>0.05), and no obvious adverse reactions were observed in either of the two groups. CONCLUSIONS: Phloroglucinol combined with parecoxib is more effective and safer than phloroglucinol alone in relieving postoperative cystospasm after TURP.

[Safety and effectiveness of GreenLight 120-W laser photoselective vaporization of the prostate for benign prostatic hyperplasia: A meta-analysis].

OBJECTIVE: To evaluate the safety and effectiveness of GreenLight 120-W laser photoselective vaporization of the prostate (PVP) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). METHODS: We searched PubMed, Medline, Embase, Cochrane Library, Wanfang, CNKI, and VIP for randomized control trials and their references addressing 120-W PVP versus TURP in the treatment of BPH. Based on the inclusion and exclusion criteria, two reviewers independently accomplished the screening, quality assessment, and data extraction of the identified studies and performed meta-analyses using RevMan 5.2. RESULTS: Totally, 6 randomized control trials were included in this analysis, involving 703 cases, 351 treated by PVP and 352 by TURP. Compared with TURP, PVP showed significantly decreased time of catheterization (by 32. 55 hours, 95% CI 15.3 -49.8, P < 0.01), hospital stay (by 1.85 days, 95% CI 1.2-2.5, P < 0.01), and intraoperative blood loss (by 15.6 g/L, 95% CI 10.0-21.2, P < 0.01), but increased time of operation (by 9.37 minutes, 95% CI 5. 1-13.6, P < 0.01). There was also a significant reduction in blood transfusion, TUR syndrome, and capsular perforation in the PVP group. At 12 months after surgery, no statistically significant differences were found between the two groups in the improvement of maximum urinary flow rate, IPSS, postvoid residual, and sexual function. CONCLUSION: GreenLight 120-W laser PVP is a safe and effective procedure for the treatment of BPH, with similar effectiveness to TURP but less blood loss, shorter time of catheterization and hospital stay, and lower incidences of blood transfusion, TUR syndrome and capsular perforation.

Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway.

The high mobility group box 1 (HMGB1), which is a highly conserved and evolutionarily non-histone nuclear protein, has been shown to associate with a variety of biological important processes, such as transcription, DNA repair, differentiation, and extracellular signalling. High HMGB1 expression has been reported in many cancers, such as prostate, kidney, ovarian, and gastric cancer. However, there have been few studies of the function of HMGB1 in the malignant biological behaviour of bladder urothelial carcinoma (BUC), and the potential mechanism of HMGB1 in the pathogenesis of BUC remains unclear. Thus, in this study, we constructed plasmid vectors that are capable of synthesizing specific shRNAs targeting HMGB1 and transfected them into BUC cells to persistently suppress the endogenous gene expression of HMGB1. The expression of HMGB1, the bioactivity of BUC cells, including proliferation, apoptosis, cell cycle distribution, migration and invasion, and the effects of HMGB1 knockdown on downstream signalling pathways were investigated. Our data suggest that HMGB1 promotes the malignant biological behaviour of BUC, and that this effect may be partially mediated by the NF-κB signalling pathway. HMGB1 may serve as a potential therapeutic target for BUC in the future.

Primary non-Hodgkin's lymphoma of the prostate with intractable hematuria: A case report and review of the literature.

Cases of primary non-Hodgkin's lymphoma of the prostate are globally rare. The present study reports a case of prostatic diffuse large B-cell lymphoma (DLBCL) with intractable hematuria in a 75-year-old male. The patient presented with difficulties in urination and gross hematuria. A prostate biopsy was performed immediately, followed by conservative treatment for bleeding. A bilateral iliac arteriography and chemoembolization were then performed as emergency procedures under local anesthesia due to significant bleeding and a sharply decreased blood pressure, indicating the failure of the conservative treatment. Consequently, the bleeding was effectively controlled. Pathological examination of the prostate biopsy confirmed the presence of a DLBCL of non-germinal center B-cell origin. Immunohistochemical examination demonstrated cluster of differentiation (CD)20(++), CD3(+), leukocyte common antigen(+++), B-cell lymphoma-2(+) and prostate-specific antigen(-) results. Due to the poor general condition and low hemoglobin levels of the patient, a low-dose Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy regimen was administered. Subsequent to three courses of chemotherapy, the patient achieved complete remission. In conclusion, combining R-CHOP and bilateral selective iliac arterial chemoembolization could be a safe and effective way to treat patients with non-Hodgkin's lymphoma of the prostate and intractable hematuria.

Solitary fibrous tumor of the spermatic cord: A case report and literature review.

A 31-year-old male patient with a six-year history of left inguinoscrotal swelling was admitted to the Second Xiangya Hospital (Changsha, China). The mass was not found to be associated with intraperitoneal pressure. Ultrasonography and computed tomography examinations demonstrated several solid, botryoidal masses involving the spermatic cord, with limited capacity of mobility. The demarcation between the masses and the left testicle was clear; thus, the masses were removed by a left spermatic cord tumor resection via a left inguinal approach, under epidural anesthesia. Positive staining of the tumor markers, CD34+, CD99+ and Bcl-2+, was confirmed by pathological examination following surgery, and a solitary fibrous tumor of the spermatic cord was diagnosed. No recurrence and metastasis were observed in the patient during the subsequent 25-month follow-up period.