Background: This study aims to study how gold nanoparticles (AuNPs) function in the recruitment and polarization of tumor-associated macrophages (TAMs) in hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). Methods: Phorbol ester (PMA)-treated THP-1 cells were cocultured with LNCaP or PC3 cells to simulate TAMs. Macrophage M2 polarization levels were detected using flow cytometry and M2 marker determination. ATG5 expression was detected by western blotting. Luciferase reporter assay was used to analyze the N6-methyladenosine (m6A) site activity of ATG5 3' untranslated regions (3'-UTRs). Methylated RNA immune precipitation (MeRIP)-quantitative polymerase chain reaction (qPCR) was performed to determine the m6A levels at ATG5 3'-UTR. Xenograft mouse models were used to determine the function of AuNPs in vivo. Results: Macrophages exhibited reduced M2 polarization in both HSPC and CRPC cells after AuNP treatment which was prevented by induction of autophagy. AuNP treatment decreased the m6A levels in the 3'-UTR of ATG5. Mutational analysis of potential m6A sites within ATG5 3'-UTR revealed that these sites were required for AuNP regulation, indicating that AuNPs inhibited ATG5 levels in an m6A-dependent manner. The mouse model revealed that AuNPs significantly reduced the M2 polarization of TAMs in an autophagy-dependent manner in vivo. This suggests that AuNPs inhibit tumor growth in vivo partially through targeting M2 TAM. Conclusion: The ATG5/autophagy pathway is inhibited by AuNP treatment in an METTL3/m6A-dependent manner. AuNPs inhibit the TAM M2 polarization in HSPC and CRPC by inhibiting ATG5/autophagy.
OBJECTIVES:Takayasu's arteritis (TAK) is a progressive autoimmune vasculitis that mainly affects the aorta and its major branches. While recent studies have identified proinflammatory T cells, including Th1 and Th17 cells, as the dominant infiltrates in the arterial adventitia, mechanisms underpinning the maintenance of such vasculogenic T cells remain obscure.METHODS:75 patients with TAK and 30 age-matched healthy controls were enrolled in this study. CD4 T cells from TAK patients were activated with anti-CD3/CD28 beads to mimic vasculogenic T cells. The survival of T cells was detected by quantifying Annexin-V+7-AAD+ fractions. Expression and activity of AMP-activated protein kinase (AMPK) were determined using phosflow cytometry and immunoblots. Specific inhibitors and shRNA were applied to block the function of AMPK and Notch1, while erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to reflect the disease activity of TAK patients.RESULTS:T cells from TAK patients undergo spontaneous differentiation into vasculogenic proinflammatory T cells with prolonged survival capacity. Mechanistic explorations uncover AMPK hyperactivity in such T cells from TAK patients, promoting mitochondrial metabolism and their survival. Such AMPK hyperactivity results from the robust Notch1 activity in TAK T cells. Accordingly, T cell-intrinsic phosphor-AMPK reflects the disease activity in clinical TAK patients.CONCLUSIONS:AMPK hyperactivity is essential for maintaining the vasculogenic proinflammatory T cells in TAK patients, serving as a promising therapeutic target for TAK management.
To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells. For in vitro experiments, T24 cells were stimulated with Andro (0–40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting. Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01). Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.
并发于同侧肾上腺皮质的原发性醛固酮增多症腺瘤(Conn腺瘤)和髓质的嗜铬细胞瘤临床罕见,仅有少数病例报道.吉林大学第一医院2019年收治了1例以肢体乏力和胸痛起病的原发性醛固酮增多症腺瘤合并嗜铬细胞瘤患者,现报告如下.
The specific cytotoxic effects of nanoparticles on tumor cells may be used in future antitumor clinical applications. Gold nanoparticles (AuNPs) have been reported to produce potent cytotoxic effects; however, the precise mechanism is unclear. In this study, AuNPs were synthesized; the average size of the particles was 62.2 +/- 6 nm with smooth surface and multiple shapes, which were determined using transmission electron microscopy and field emission scanning electron microscopy. The selected area electron diffraction patterns suggested that the synthesized AuNPs were crystalline. The X-ray photoelectron spectroscopy (XPS) spectrum of the synthesized AuNPs has presented an intense peak at 100 eV, signifying the entire composition of Au in the developed AuNPs. This synthesized AuNPs showed the most potent efficacy in prostate cancer cells, regardless of whether or not they were androgen dependent. Secretome determinations using two-dimensional difference in-gel electrophoresis (2D-DIGE), followed by enzyme-linked immunosorbent assay and quantitative reverse transcriptase-polymerase chain reaction validations, have identified a series of secretory proteins that were dysregulated by AuNP treatment in prostate cancer cells, many of which are highly involved in cytokine-chemokine functions, including CXCL3, interleukin-10, CCL2, and matrix metalloproteinase 9 (MMP9). Further research on molecular mechanism has indicated that AuNPs can trigger the secretion of anticancer factors and myeloid cell-polarizing factors from tumor cells through MMP9 inhibition. These results have clearly signified the cytotoxic potential of AuNPs for treating prostate cancer and may provide a novel direction for prostate cancer therapy in the future.
Chronic kidney disease (CKD) is a complex disease in which the renal function is compromised chronically. Many studies have indicated the crosstalk between the tubule and the glomerulus in CKD progression. However, our understanding of the interaction of tubular and glomerular injury remains incomplete. In this study, we applied a meta-analysis approach on the transcriptome of the tubules and glomeruli of CKD patients to identify differentially expressed genes (DEGs) signature. Functional analysis of pathways and Gene Ontology found that tubular DEGs were mainly involved in cell assembly and remodeling, glomerular DEGs in cell proliferation and apoptosis, and overlapping DEGs mainly in immune response. Correlation analysis was performed to identify the associated DEGs in the tubules and glomeruli. Secreted protein comparison and verification experiments indicated that WFDC2 from the tubule could downregulate PEX19 mRNA and protein levels at the glomeruli in diabetic kidney disease (DKD). This study revealed the distinctive pathways of the tubules and glomeruli and identified interacted genes during CKD progression.
Background: Bladder cancer (BCa) has the highest incidence of aggressive malignant tumors in the urogenital system and is the ninth most common cancer worldwide. Immune function-related genes (IFRGs), which are plentiful in immune cells and the immune microenvironment (IME), have the potential to assess prognosis and predict the efficacy of immunotherapy. A complete and significant immunogenomic analysis based on abundant BCa genetic samples from The Cancer Genome Atlas (TCGA) will provide insight into the field. Results: A total of 57 differentially expressed IFRGs were significantly associated with the clinical outcomes of patients with BCa. Functional enrichment analysis showed that these genes actively participated in the KEGG pathway of human cytomegalovirus infection. Based on the IFRGs (CALR, MMP9, PAEP, RBP7, STAT1, CACYBP, ANHAK, RAC3, SLIT2, EDNRA, IGF1, NAMPT, NTF3, PPY, ADRB2 and SH3BP2), the risk scores were calculated to predict survival and reveal the relationships with age, sex, grade, staging, T-stage, N-stage, and M-stage. Interestingly, IFRG-based risk scores (IRRSs) reflected the infiltration of several types of immune cells. The expression of CACYBP was more significant in grade 3, T3 and T4 stages than in earlier grades and T-stages. Conclusion: Our results highlighted some sIFRGs with remarkable clinical relevance, showed the driving factors of the immune repertoire, and illustrated the significance of IFRG-based individual immune features in the identification, monitoring, and prognosis of patients with BCa. Methods: Based on the TCGA dataset, we integrated the expression profiles of IFRGs and overall survival (OS) in 430 patients with BCa. Differentially expressed IFRGs and survival-related IFRGs (sIFRGs) were highlighted by calculating the difference algorithm and COX regression analysis in patients with BCa. Based on computational biology, the potential molecular mechanisms and characteristics of these IFRGs were also explored. Using multivariate Cox analysis, new risk scores based on immune-related genes were developed. The expression of CACYBP was verified by qPCR, western blot and immunohistochemistry. The relations between CACYBP and clinical features were proven by immunohistochemistry.
Xp11. 2易位/TFE3基因融合相关性肾癌( Xp11. 2 RCCs)临床少见,多以个案形式报道,临床医生对于此病的认知仍较有限. 现将我院2017年6 月~2018 年3 月收治并经病理确诊为Xp11. 2 RCCs的5例病例进行汇总,并对相关文献进行复习,旨在提高临床医生对于该病的认识.
Abstract Background The appropriate application of various treatment for upper tract urothelial carcinomas (UTUCs) is the key to prolong the survival of UTUC patients. Herein, we used data in our database to assess the oncological outcomes between partial ureterectomy (PU) and radical nephroureterectomy (RNU). Methods From 2007 to 2014, 255 patients with UTUC undergoing PU or RNU in our hospital database were investigated. Perioperative, postoperative data, and pathologic outcomes were obtained from our database. Cancer-specific survival (CSS) was assessed through the Kaplan-Meier method with Cox regression models to test the effect of these two surgery types. Results The mean length of follow-up was 35.8 months (interquartile range 10–47 months). Patients with high pT stage (pT2–4) suffered shorter survival span (HR: 9.370, 95% CI: 2.956–29.697, P < 0.001). There were no significant differences in CSS between PU and RNU (P = 0.964). In the sub-analysis, CSS for RNU and PU showed no significant difference for pTa–1 or pT2–4 tumor patients (P = 0.516, P = 0.475, respectively). Conclusions PU is not inferior to RNU in oncologic outcomes. Furthermore, PU is generally recognized with less invasive and better renal function preservation compared with RNU. Thus, PU would be rational for specific patients with UTUCs.
The objective of this study was to investigate soluble epidermal growth factor receptor (sEGFR), soluble vascular endothelial growth factor receptor 1 (sFlt-1), soluble endoglin (sEndoglin) and placenta growth factor (PLGF) concentrations in normotensive, preterm and term preeclamptic pregnancies' serum and thus to specify the clinical utility of these biochemical markers in monitoring severity and intrauterine growth retardation of preterm preeclampsia. 172 pregnant women were divided into the following groups: preterm preeclampsia, preterm control, term preeclampsia and term control. Preterm preeclampsia patients were stratified with severe feature (n = 50) and without severe feature (n = 22). sEGFR, sEndoglin and PLGF were assessed using Luminex multiplex immunoassay, whilesFlt-1 was assessed using ELISA. sEGFR was significantly lower in preterm preeclampsia than matched control (p < 0.001) and mildly lower in term preeclampsia than matched control (p < 0.01). On contrary, sFlt-1 was significantly higher in preterm preeclampsia than matched control (p < 0.001) and mildly higher in term preeclampsia than matched control (p < 0.01). sFlt-1, sFlt-1/sEGFR and sFlt-1/PLGF were positively correlated with the severity of preterm preeclampsia (P < 0.001, R value >= 0.6), especially sFlt-1/sEGFR had the highest R value (R value = 0.711) among them. Furthermore, sEndoglin and the ratio of sEndoglin/sEGFR were associated with neonatal birth weight small for gestational age (SGA, n = 25) in preterm preeclampsia group. Conclusions: The ratio of sFlt-1/sEGFR could be used as a novel candidate biochemical marker in monitoring the severity of preterm preeclampsia. sEndoglin and sEGFR may be involved in the pathogenesis of SGA in preterm preelampsia.
BACKGROUND:Preeclampsia is a multi-system disorder in pregnancy which has no effective treatment. The diagnosis of preeclampsia is based on clinical presentation and routine laboratory tests.OBJECTIVE:This study aimed at identifying serum protein markers for diagnosis of preeclampsia and predicting its severe features.STUDY DESIGN:In total, 172 pregnant women were enrolled in this study including 110 subjects with preeclampsia and 62 normotensive subjects. Eleven serum proteins (VEGF, sFlt-1, sEndoglin, PlGF, sEGFR, prolactin, PTX3, PAI-1, NGAL, IL-27, COX-2) were assessed using Luminex multiplex immunoassay and ELISA.RESULTS:The levels of seven proteins (sFlt-1, VEGF, sEndoglin, sEGFR, PlGF, NGAL, COX-2) correlated with preeclampsia, and 4 proteins (VEGF, sEndoglin, PlGF, sEGFR) were identified as independent factors associated with preeclampsia. The levels of three proteins (sEndoglin, PTX3, sFlt-1) correlated with severe features of preeclampsia, and three variables (serum creatinine, platelet count and sEndoglin) were identified as independent factors in predicting severe features of preeclampsia.CONCLUSIONS:A combination of serum protein markers (VEGF, sEndoglin, PlGF, sEGFR) and clinical variables (serum creatinine, platelet count and sEndoglin) could be used as analytical tool in diagnosis of preeclampsia and its severe features, respectively. Serum sEGFR, a novel biomarker in preeclampsia, may be involved in the pathogenesis of preeclampsia.
This present case report describes a 64-year-old female patient with type 2 diabetes mellitus who also had emphysematous pyelonephritis (EPN) and emphysematous cystitis (EC). Computed tomography revealed well defined emphysematous pyelonephritis and cystitis. Broad-spectrum antibiotic and percutaneous drainage of the right kidney were used as part of a conservative management regimen. The patient achieved clinical recovery and was discharged 12 days after admission. Furthermore, 13 other cases of EPC and EC that were reported between 1962 and 2017 were reviewed and discussed. The overall mortality was 15.4% (two of 13 patients), compared with 25% for EPN alone or 7.4% for EC alone as reported in the literature. The primary pathogen identified in the 13 patients was Escherichia coli (53.8%). All 13 patients were treated with antibiotics.
患者男,73 岁,因体检发现右肾囊肿 4 年,复查发现增大 10 d 于 2018 年 1 月 21 日入住吉林大学第一医院泌尿外科. 患者 4 年前于当地医院体检时行彩超发现右肾囊肿,直径约 4 cm,未予治疗,10 d 前复查彩超发现囊肿增大,为进一步诊治来我院就诊. 既往患高血压 30 年,口服卡托普利片,平时测量血压 140 /90 mmHg (1 mmHg =0.133 kPa).糖尿病病史3 年,口服二甲双胍,平时空腹血糖 7.0 mmol /L.否认肿瘤家族史,否认致癌物接触史.
Dear Editor, The concept of dedifferentiated liposarcoma (DDL) was first proposed by Evans in 1979.1 Liposarcomas, including DDL and well-differentiated liposarcoma (WDL), occur most frequently in 50- to 70-year-old men within the retroperitoneum or extremities. DDL has a propensity for local recurrence, but distant metastasis is rare. Retroperitoneal DDL has a significantly worse prognosis than disease at other locations.2 As paratesticular DDL is a rare entity, clinicians need to differentiate it from other common scrotal neoplasms or swelling diseases. Herein, we describe a case of recurrent paratesticular DDL after contralateral radical orchiectomy to improve understanding of this disease. Informed consent is obtained from the patient and this study is adherence to Declaration of Helsinki. The protocol of this manuscript was approved by the Human Research Ethics Committee in the First Hospital of Jilin University, Changchun, China. A 53-year-old man felt distending pain around his right testicle for 20 days. Palpation revealed the absence of the left testis, a well-defined solid mass in the right scrotum, and a larger tough mass in the suprapubic region. A transillumination test of the scrotum was negative, and other physical examinations were normal. A left orchiectomy and regional lymph node dissection was performed due to the patient having “testicular cancer” 2 years ago. His previous pathological report documented a left testicular malignant tumor that was considered as a high-grade sarcoma, but without immunohistochemistry (IHC). Ultrasound (GE LOGIQ E9; GE Healthcare, Wauwatosa, WI, USA) revealed two partially fused hypoechoic nodules above the right epididymis (1.4 cm × 1.1 cm and 1.3 cm × 0.8 cm) and one suprapubic hypoechoic nodule (2.0 cm × 1.3 cm). Bilateral inguinal lymph nodes (range: 0.4–1.0 cm) could be seen by ultrasonography. Abdominal computed tomography (CT; PHILIPS Brilliance 64 CT Scanner; PHILIPS, Best, the Netherlands) scanning revealed subcutaneous fat gap turbidity and a high-density mass (0.5–1.6 cm) above the pubic symphysis (Figure 1). Additional pulmonary CT and whole-body bone scans (GE Discovery NM/CT 670; GE Healthcare) suggested no distant metastasis. Laboratory results including tumor markers (carcinoembryonic antigen [CEA], CA-242, alpha fetoprotein [AFP], free prostate-specific antigen [fPSA], total prostate-specific antigen [tPSA], CA125, cytokeratin 19 fragment [CYFRA21-1], neuron-specific enolase [NSE], CA-199, human chorionic gonadotropin [HCG], squamous cell carcinoma antigen [SCCA], and CA-724) and other routine serological tests were normal.Figure 1: Abdominal CT, gross pathology, and histopathology results of the tumors. (a) Abdominal CT revealed a subcutaneous mass lesion above the pubic symphysis. (b) Gross pathologic examination revealed that the right intrascrotal dissection block contained two partially fused neoplasms, partial testicle, partial epididymis, and partial spermatic cord (below) and the suprapubic dissection block contained one complete neoplasm and its surrounding fat tissue (above). (c) Postoperative H and E ×200 staining showed WDL components. (d) Postoperative H and E ×100 staining showed DDL components. Preoperative bioptic immunohistochemistry findings ×200 with (e) S-100, (f) Vimentin, (g) CD34, and (h) Ki-67 antibody showed DDL characteristics for samples from both sites. Scale bars = 100 μm in c–h. S-100 and Vimentin are markers for lipoblast; CD34 is a marker for dedifferentiation degree. CT: computed tomography; DDL: dedifferentiated liposarcoma; H and E: hematoxylin and eosin; WDL: well-differentiated liposarcoma.To clarify the diagnosis, the patient underwent ultrasound-guided percutaneous puncture (GE LOGIQ S8; GE Healthcare) on the suprapubic and paratesticular masses. Pathological results of both sites suggested malignant tumors that originated from mesenchymal tissue. Combining his medical history and IHC results, diagnoses of paratesticular DDL and suprapubic undifferentiated sarcoma were made. IHC of patient samples showed positive Vimentin and CD34 staining, suspected positive S-100 (several cells at the suprapubic site) and Ki-67 (>20%) staining, and negative Desmin, smooth muscle (SMA), CD117, Dog-1, and CK-pan staining (Figure 1). Afterward, the right paratesticular tumors and suprapubic abdominal wall tumor were resected. Resection of the right paratesticular tumors (7 cm × 3.5 cm × 2 cm) was done using the inguinal canal approach. During resection of the suprapubic tumor (7.5 cm × 6.5 cm × 4.5 cm), hard nodules located adjacent to the tumor (3 cm × 2 cm × 1.5 cm) and beneath the previous incision site (4 cm × 2.5 cm × 1.5 cm) were simultaneously removed (Figure 1). Both the surgery and the postoperative recovery were favorable. The final pathological results after surgery suggested DDL at four sites (Figure 1). At a 9-month telephone follow-up, he had gone through three cycles of doxorubicin (ADRIAMYCIN®; Pfizer, New York, NY, USA) and ifosfamide (HOLOXAN®; Baxter Oncology GmbH, Halle, Germany) (A/I) chemotherapy regime (doxorubicin 75 mg m−2 per day for day 1–3, plus ifosfamide 2.5 g m−2 per day for day 1–4), and no signs of recurrence or metastasis had been found. Paratesticular masses are common clinical scenarios for urologists and andrologists. A recent study analyzed 138 orchiectomy specimens for paratesticular soft-tissue masses over 17 years. The most common malignancies were rhabdomyosarcoma, liposarcoma, and leiomyosarcoma. The most common benign neoplasm was spermatic cord lipoma, followed by leiomyoma and hemangioma. In young patients, paratesticular malignancies are frequently rhabdomyosarcomas, while in older patients, they are liposarcomas. Most benign lesions were incidental, while malignancies were not.3 Preoperative biopsy should be performed if malignancy cannot be excluded. DDL presents as a heterogeneous mass containing both atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) components and nonlipogenic high-grade sarcoma components. Before IHC and fluorescence in situ hybridization (FISH) were widely used, retroperitoneal DDL was often misdiagnosed as either ALT/WDL or malignant fibrous histiocytoma. IHC and FISH detecting mouse double-minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are currently the standard criteria for DDL.4 A recent report noted that using p16 in combination with MDM2 and CDK4 for IHC could increase diagnostic specificity by helping to discriminate ALT/WDL and DDL.5 Therefore, preoperative biopsy is essential to reduce unnecessary orchiectomies, and IHC is critical for diagnosing uncommon paratesticular tumors such as DDL. If conditions permit, MDM2 and CDK4 staining should be performed. En bloc resection of primary DDL is important for improving prognosis because of its propensity for local recurrence. In this case, we inferred that the hard nodule located beneath the previous incision was local recurrence; the suprapubic and inguinal masses were metastatic tumors either from the left intrascrotal tumor 2 years ago or from the right paratesticular DDL. Radiotherapy is required if complete resection fails. Chemotherapy is suggested for metastatic DDL. Laboratory studies have suggested that targeted therapy, such as fibroblast growth factor receptor (FGFR) inhibitors and tyrosine kinase inhibitors, might work for DDL.67 Radiotherapy, chemotherapy, and targeted therapy are clinical options for DDL. Surgical resection remains the mainstay of DDL treatment, as medical options for patients with aggressive relapse or metastasis are limited.2 Approximately 8.9% of atypical lipomatous tumors recurred locally, of which 50% recurred after 60 months; in total, 17% of de novo DDLs recurred within 60 months of presentation.8 In a study that reviewed 148 DDL patients, distant metastases were observed in 44 of 148 patients (29.7%), 9 of 44 (20.5%) at presentation, while 35 of 44 patients (79.5%) developed them later, with a median interval of 8 months. The median survival time was 28 months for patients with metastases and 38 months for patients without metastases.9 Therefore, regular long-term follow-ups are necessary. Based on the current data, follow-up should last over 5 years, and the interval should be every 6 months within the first 5 years and every 12 months afterward. Magnetic resonance imaging (MRI) scanning is highly recommended for follow-up because it is sensitive enough to detect lipomatous lesions. In conclusion, paratesticular DDL is an extreme rare entity. Preoperative biopsy is essential to confirm the diagnosis. Complete surgical resection is a sine qua non for DDL treatment, but chemotherapy, radiotherapy, and targeted therapy can also be considered. Finally, long-term follow-up is necessary to improve prognosis. AUTHOR CONTRIBUTIONS JW and YPD carried out the study concept, design, data gathering, and manuscript drafting. SXL carried out medical records and follow-up. JHH and CXW carried out surgery. CXW supervised the manuscript revision and took responsibility for the integrity and accuracy of the data. All authors read and approved the final manuscript. COMPETING INTERESTS All authors declared no competing interests.
Ulinastatin [or called as urinary trypsin inhibitor (UTI)] plays a role in regulating neurological deficits evoked by transient cerebral ischemia. However, the underlying mechanisms still need to be determined. The present study was to examine the effects of UTI on autophagy, Nrf2-ARE and apoptosis signal pathway in the hippocampus in the process of neurological functions after cerebral ischemia using a rat model of cardiac arrest (CA). CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Western blot analysis was employed to determine the expression of representative autophagy (namely, Atg5, LC3, Beclin 1), p62 protein (a maker of autophagic flux), and Nrf2-ARE pathways. Neuronal apoptosis was assessed by determining expression levels of Caspase-3 and Caspase-9, and by examining terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL). The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats. Our results show that CA amplified autophagy and apoptotic Caspase-3/Caspase-9, and downregulated Nrf2-ARE pathway in the hippocampus CA1 region. Systemic administration of UTI attenuated autophagy and apoptosis, and largely restored Nrf2-ARE signal pathway following cerebral ischemia and thereby alleviated neurological deficits with increasing survival of CA rats. Our data suggest that UTI improves the worsened protein expression of autophagy and apoptosis, and restores Nrf2-ARE signals in the hippocampus and this is linked to inhibition of neurological deficiencies in transient cerebral ischemia. UTI plays a beneficial role in modulating neurological deficits induced by transient cerebral ischemia via central autophagy, apoptosis and Nrf2-ARE mechanisms.
Purpose: The present study was designed to investigate the risk factors affecting the conversion to open surgery in retroperitoneal laparoscopic nephrectomy of nonfunctioning renal tuberculosis (TB). Patients and Methods: The records of 144 patients who underwent a retroperitoneal laparoscopic nephrectomy procedure by a single surgeon were retrospectively reviewed. The following factors, including age, sex, body mass index (BMI), diabetes status, hypertension status, side of kidney, size of kidney, degree of calcification, mild perirenal extravasation, contralateral hydronephrosis, the time of anti-TB, and surgeon experience were analyzed. Univariate and multivariate logistic regression analyses were used for statistical assessment. Results: Twenty-three patients were converted to open surgery and the conversion rate was 15.97%. In univariate analysis, BMI >= 35 kg/m(2) (p = 0.023), hypertension (p = 0.011), diabetes (p = 0.003), and kidney size (p = 0.032) were the main factors of conversion to open surgery. Sex, age, side, anti-TB time, calcification, mild extravasation, and surgeon experience were not significantly related. In multivariate regression analysis, BMI >= 35 kg/m(2), hypertension, diabetes, and enlargement of kidney were the most important factors for conversion to open surgery. Conclusions: Depending on the results achieved by a single surgeon, BMI >= 30 kg/m(2), diabetes, hypertension, and enlargement of kidney significantly increased the conversion risk in retroperitoneal laparoscopic nephrectomy for nonfunctioning renal TB.
Adrenocortical oncocytoma is an extremely rare tumor of the adrenal gland. Its diagnostic criteria and biological behavior has not yet reached a consensus. The purpose of this study is to investigate the clinical characteristics of adrenocortical oncocytoma.The clinical data from 11 cases of adrenocortical oncocytoma were retrospectively analyzed. Five patients found the tumor incidentally during the healthy examination, and 3 cases found the tumor during the diagnostic work-up for the evaluation of flank pain or hypertension. A female patient manifested virilization, and Cushing's syndrome showed in two patients. The tumor diameter was ranging from 2.0-13.0 cm.The serum cortisol, plasma aldosterone and catecholamine metabolites were used to evaluate the function of the tumors, and enhanced CT scan was used to confirm the tumor boundary, enhancement, and lymph nodes condition.Seven cases underwent laparoscopic adrenal tumor resection, 4 patients underwent open surgery. Pathological report indicated adrenocortical oncocytoma in all cases, three of which were potentially malignant.The patients were followed up for 19-72 months, no local recurrence and distant metastases were detected in 3 cases of malignant potential cases.The majority of adrenocortical oncocytoma with or without function are benign, and close follow-up observation is essential.
Tripartite motif 44 (TRIM44), a member of the TRIM protein family, has been shown to play a role in tumor development and progression. However, the potential involvement of TRIM44 in prostate cancer has not been fully explored. Therefore, in the present study, we analyzed the expression of TRIM44 in prostate cancer and assessed the role of TRIM44 in the progression of prostate cancer. Our results showed that the expression of TRIM44 was significantly upregulated in human prostate cancer cell lines. In addition, knockdown of TRIM44 significantly inhibited the proliferation, migration, and invasion of prostate cancer cells in vitro, as well as attenuated the tumor growth in vivo. Mechanistic studies showed that knockdown of TRIM44 significantly reduced the levels of phosphorylated PI3K and Akt in PC-3 cells. In conclusion, this study provided evidence that knockdown of TRIM44 inhibited proliferation and invasion in prostate cancer cells, at least in part, through the inactivation of the PI3K/Akt signaling pathway. These results suggest that TRIM44 may be a potential therapeutic target for the treatment of prostate cancer.
Rationale: Adrenocortical oncocytoma is an extremely rare tumor of the adrenal gland. Its diagnostic criteria and biological behavior has not yet reached a consensus. The purpose of this study is to investigate the clinical characteristics of adrenocortical oncocytoma. Patient concerns: The clinical data from 11 cases of adrenocortical oncocytoma were retrospectively analyzed. Five patients found the tumor incidentally during the healthy examination, and 3 cases found the tumor during the diagnostic work-up for the evaluation of flank pain or hypertension. A female patient manifested virilization, and Cushing's syndrome showed in two patients. The tumor diameter was ranging from 2.0-13.0cm. Diagnoses: The serum cortisol, plasma aldosterone and catecholamine metabolites were used to evaluate the function of the tumors, and enhanced CT scan was used to confirm the tumor boundary, enhancement, and lymph nodes condition. Interventions: Seven cases underwent laparoscopic adrenal tumor resection, 4 patients underwent open surgery. Pathological report indicated adrenocortical oncocytoma in all cases, three of which were potentially malignant. Outcomes: The patients were followed up for 19-72 months, no local recurrence and distant metastases were detected in 3 cases of malignant potential cases. Lessons: The majority of adrenocortical oncocytoma with or without function are benign, and close follow-up observation is essential.
Ulinastatin [urinary trypsin inhibitor (UTI)] plays an important role in the protection of organs against ischemic injury during severe inflammation. The purposes of this study were to examine the effects of UTI on the levels of pro-inflammatory cytokines (PICs) and protein expression of PIC receptors in the neocortex and hippocampus CA1 region of rats after transient global ischemia induced via cardiac arrest (CA). Specifcally, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed. CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were employed to determine PICs and their receptors in the neocortex and hippocampus. Our results show that IL-1β, IL-6 and TNF-α were significantly elevated in the neocortex and hippocampal CA1 field after CA. This was accompanied with an increase in PIC receptors, namely IL-1R, IL-6R and TNFR1. Systemic injection of UTI attenuated the amplification of PIC signal pathways in these brain regions. UTI also improved the modified Neurological Severity Score and brain tissue edema in CA rats. Notably, UTI resulted in an increase in survival of CA rats as compared to CA rats without treatment. In conclusion, UTI plays a beneficial role in modulating transient global ischemia induced by CA by altering PIC signal mechanisms, but further studies are needed to draw more firm conclusions.