Regulation of cancer cell ferroptosis by PTRF/Cavin-1.

Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.

Identification of IRAK1BP1 as a candidate prognostic factor in lung adenocarcinoma.

Introduction: Lung cancer is one of the major causes of cancer-related mortality worldwide. High-throughput RNA sequencing (RNA-seq) of surgically removed tumors has been used to identify new biomarkers of lung cancer; however, contamination by non-tumor cells in the tumor microenvironment significantly interferes with the search for novel biomarkers. Tumor organoids, as a pre-clinical cancer model, exhibit similar molecular characteristics with tumor samples while minimizing the interference from other cells. Methods and Results: Here we analyzed six RNA-seq datasets collected from different organoid models, in which cells with oncogenic mutations were reprogrammed to mimic lung adenocarcinoma (LUAD) tumorigenesis. We uncovered 9 LUAD-specific biomarker genes by integrating transcriptomic data from multiple sources, and identified IRAK1BP1 as a novel predictor of LUAD disease outcome. Validation with RNA-seq and microarray data collected from multiple patient cohorts, as well as patient-derived xenograft (PDX) and lung cancer cell line models confirmed that IRAK1BP1 expression was significantly lower in tumor cells, and had no correlation with known markers oflung cancer prognosis. In addition, loss of IRAK1BP1 correlated with the group of LUAD patients with worse survival; and gene-set enrichment analysis using tumor and cell line data implicated that high IRAK1BP1 expression was associated with suppression of oncogenic pathways. Discussion: In conclusion, we demonstrate that IRAK1BP1 is a promising biomarker of LUAD prognosis.

HucMSC-EVs Facilitate In Vitro Development of Maternally Aged Preantral Follicles and Oocytes.

Follicle developmental capacity and oocyte quality decline with advanced maternal age. Extracellular vesicles from human umbilical cord mesenchymal stem cells (HucMSC-EVs) act as a potential therapeutic product in the treatment of age-related ovarian dysfunction. In vitro culture (IVC) of preantral follicles is a useful method for understanding the mechanism of follicle development and is a promising means for improving female fertility. However, whether HucMSC-EVs have beneficial effects on aged follicle development during IVC has not yet been reported. Our research demonstrated that follicular development with single-addition withdrawal of HucMSC-EVs was better than that with continuous treatment with HucMSC-EVs. HucMSC-EVs facilitated the survival and growth of follicles, promoted the proliferation of granulosa cells (GCs), and improved the steroid hormone secretion of GCs during IVC of aged follicles. Both GCs and oocytes could uptake HucMSC-EVs. Moreover, we observed elevated cellular transcription in GCs and oocytes after treatment with HucMSC-EVs. The RNA sequencing (RNA-seq) results further validated that the differentially expressed genes are related to the promotion of GC proliferation, cell communication, and oocyte spindle organization. Additionally, the aged oocytes displayed a higher maturation rate, presented less aberrant spindle morphology, and expressed a higher level of the antioxidant protein Sirtuin 1 (SIRT1) after treatment with HucMSC-EVs. Our findings suggested that HucMSC-EVs can improve the growth and quality of aged follicles and oocytes in vitro through the regulation of gene transcription, which provides evidence for HucMSC-EVs as potential therapeutic reagents to restore female fertility with advanced age.

Asymmetric Cell Division and Tumor Heterogeneity.

Asymmetric cell division (ACD) gives rise to two daughter cells with different fates after mitosis and is a fundamental process for generating cell diversity and for the maintenance of the stem cell population. The cancer stem cell (CSC) theory suggests that CSCs with dysregulated self-renewal and asymmetric cell division serve as a source of intra-tumoral heterogeneity. This heterogeneity complicates the diagnosis and treatment of cancer patients, because CSCs can give rise to aggressive clones that are metastatic and insensitive to multiple drugs, or to dormant tumor cells that are difficult to detect. Here, we review the regulatory mechanisms and biological significance of asymmetric division in tumor cells, with a focus on ACD-induced tumor heterogeneity in early tumorigenesis and cancer progression. We will also discuss how dissecting the relationship between ACD and cancer may help us find new approaches for combatting this heterogeneity.

TGF-ß Signaling and Resistance to Cancer Therapy.

The transforming growth factor ß (TGF-ß) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-ß signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-ß in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-ß signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-ß therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.

Therapeutic effects of the TST36 stapler on rectocele combined with internal rectal prolapse.

BACKGROUND: The most common causes of outlet obstructive constipation (OOC) are rectocele and internal rectal prolapse. The surgical methods for OOC are diverse and difficult, and the postoperative complications and recurrence rate are high, which results in both physical and mental pain in patients. With the continuous deepening of the surgeon's concept of minimally invasive surgery and continuous in-depth research on the mechanism of OOC, the treatment concepts and surgical methods are continuously improved. AIM: To determine the efficacy of the TST36 stapler in the treatment of rectocele combined with internal rectal prolapse. METHODS: From January 2017 to July 2019, 49 female patients with rectocele and internal rectal prolapse who met the inclusion criteria were selected for treatment using the TST36 stapler. RESULTS: Forty-five patients were cured, 4 patients improved, and the cure rate was 92%. The postoperative obstructed defecation syndrome score, the defecation frequency score, time/straining intensity, and sensation of incomplete evacuation were significantly decreased compared with these parameters before treatment, and the differences were statistically significant (P < 0.05). The postoperative anal canal resting pressure and maximum squeeze pressure in patients decreased compared with before treatment, and the differences were statistically significant (P < 0.05). The initial and maximum defecation thresholds after surgery were significantly lower than those before treatment, and the differences were statistically significant (P < 0.05). The postoperative ratings of rectocele, resting phase, and defecation phase in these patients were significantly decreased compared with those before treatment, and the differences were statistically significant (P < 0.05). CONCLUSION: The TST36 stapler is safe and effective in treating rectocele combined with internal rectal prolapse and is worth promoting in clinical work.

Comparing Clinicopathologic Features and Surgical Treatment of Premenopausal Breast Cancer across Italy and China: Report from a Medical Exchange Program.

BACKGROUND: This study investigated the differences in clinicopathologic features and surgical treatment between an Italian and a Chinese cohort of premenopausal women with breast cancer, and highlighted the potential advantages of international medical exchange projects. METHODS: Premenopausal women who underwent surgical treatment between 2012 and 2016 at one Italian and one Chinese institution participating in a medical exchange program were compared. Factors associated with the probability to receive mastectomy were determined via logistic analysis. Changes in surgical management at the Chinese institution in the period 2018-2019, after the exchange program, were also evaluated. RESULTS: A total of 505 patients, 318 from Italy and 187 from China, were evaluated. The Chinese patients had more frequently advanced-stage tumours, large tumour size (30.9 vs. 18.1 mm, p < 0.01), invasive carcinoma (92.5 vs. 83.3%, p < 0.01), positive axillary lymph nodes (54.5 vs. 27.4%, p < 0.01), Her-2 positivity (36.4 vs. 22.0%, p < 0.01), and high proliferative index (55.1 vs. 30.2%, p < 0.01). Positive oestrogen receptor status and rates of triple-negative breast cancer did not differ (77.0 vs. 69.5%, p = 0.09 and 14.2 vs. 16%, p = 0.56, respectively). Mastectomy rates were higher among Chinese women (85 vs. 41%, p < 0.001), whereas use of sentinel node biopsy was more frequent among Italian women (77 vs. 33%, p < 0.001). Chinese women had more than 4-fold higher risk of receiving mastectomy. In the last 2 years, the rates of breast-conserving surgery and sentinel node biopsy at the Chinese institution increased from 15 to 23%, and from 33 to 42%, respectively. CONCLUSIONS: Tumour features and surgical strategies for premenopausal breast cancer may differ significantly between Italy and China. Since the international exchange program, patients from the Chinese institution have been offered more frequently less invasive surgery. International exchange programs can help in designing epidemiological studies which may be useful for strategies to improve breast cancer management and control.

Type 2 diabetes impacts colorectal adenoma detection in screening colonoscopy.

BACKGROUND: Diabetes is associated with an increased risk of colorectal cancer (CRC). We conducted a retrospective analysis of adenoma detection rates (ADR) in initial screening colonoscopies to further investigate the role of diabetes in adenoma detection. METHODS: A chart review was performed on initial average risk screening colonoscopies (ages 45-75) during 2012-2015. Data collected included basic demographics, insurance, BMI, family history of CRC, smoking, diabetes, and aspirin use. Multivariable generalized linear mixed models for binary outcomes were used to examine the relationship between diabetes and variables associated with CRC risk and ADR. RESULTS: Of 2865 screening colonoscopies, 282 were performed on patients with type 2 diabetes (T2DM). Multivariable analysis suggested that T2DM (OR = 1.49, 95% CI:1.13-1.97, p = 0.0047) was associated with an increased ADR, as well as smoking, older age, higher BMI and male sex (all p < 0.05). For patients with T2DM, those not taking diabetes medications were more likely to have an adenoma than those taking medication (OR = 2.38, 95% CI:1.09-5.2, p = 0.03). CONCLUSION: T2DM has an effect on ADR after controlling for multiple confounding variables. Early interventions for prevention of T2DM and prescribing anti-diabetes medications may reduce development of colonic adenomas and may contribute to CRC prevention.

Development and validation of the PET-CT score for diagnosis of malignant pleural effusion.

PURPOSE: Although some parameters of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE. METHODS: One prospective derivation cohort of patients with pleural effusions (84 malignant and 115 benign) was used to develop the PET-CT score for the differential diagnosis of malignant pleural effusion. The PET-CT score was then validated in another independent prospective cohort (n = 74). RESULTS: The PET-CT parameters developed for discriminating MPE included unilateral lung nodules and/or masses with increased 18F-FDG uptake (3 points); extrapulmonary malignancies (3 points); pleural thickening with increased 18F-FDG uptake (2 points); multiple nodules or masses (uni- or bilateral lungs) with increased 18F-FDG uptake (1 point); and increased pleural effusion 18F-FDG uptake (1 point). With a cut-off value of 4 points in the derivation cohort, the area under the curve, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the PET-CT score to diagnose MPE were 0.949 (95% CI: 0.908-0.975), 83.3% (73.6%-90.6%), 92.2% (85.7%-96.4%), 10.7 (5.6-20.1), and 0.2 (0.1-0.3), respectively. CONCLUSIONS: A simple-to-use PET-CT score that uses PET-CT parameters was developed and validated. The PET-CT score can help physicians to differentiate MPE from benign pleural effusions.

Isolating pulmonary microvascular endothelial cells ex vivo: Implications for pulmonary arterial hypertension, and a caution on the use of commercial biomaterials.

Transcriptomic analysis of pulmonary microvascular endothelial cells from experimental models offers insight into pulmonary arterial hypertension (PAH) pathobiology. However, culturing may alter the molecular profile of endothelial cells prior to analysis, limiting the translational relevance of results. Here we present a novel and validated method for isolating RNA from pulmonary microvascular endothelial cells (PMVECs) ex vivo that does not require cell culturing. Initially, presumed rat PMVECs were isolated from rat peripheral lung tissue using tissue dissociation and enzymatic digestion, and cells were cultured until confluence to assess endothelial marker expression. Anti-CD31, anti-von Willebrand Factor, and anti-α-smooth muscle actin immunocytochemistry/immunofluorescence signal was detected in presumed rat PMVECs, but also in non-endothelial cell type controls. By contrast, flow cytometry using an anti-CD31 antibody and isolectin 1-B4 (from Griffonia simplicifolia) was highly specific for rat PMVECs. We next developed a strategy in which the addition of an immunomagnetic selection step for CD31+ cells permitted culture-free isolation of rat PMVECs ex vivo for RNA isolation and transcriptomic analysis using fluorescence-activated cell sorting. Heterogeneity in the validity and reproducibility of results using commercial antibodies against endothelial surface markers corresponded to a substantial burden on laboratory time, labor, and scientific budget. We demonstrate a novel protocol for the culture-free isolation and transcriptomic analysis of rat PMVECs with translational relevance to PAH. In doing so, we highlight wide variability in the quality of commonly used biological reagents, which emphasizes the importance of investigator-initiated validation of commercial biomaterials.

Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles.

Incorporation of proteins into dextran sulfate (DS)-chitosan (CS) nanoparticles (DSCS NPs) is commonly performed using entrapment procedures, in which protein molecules are mixed with DS and CS until particle formation occurs. As DS is an analog of heparin, the authors examined whether proteins could be directly incorporated into preformed DSCS NPs through a heparin binding domain-mediated interaction. The authors formulated negatively-charged DSCS NPs, and quantified the amount of charged DS in the outer shell of the particles. The authors then mixed the DSCS NPs with heparin-binding proteins (SDF-1α, VEGF, FGF-2, BMP-2, or lysozyme) to achieve incorporation. Data show that for DSCS NPs containing 100 nmol charged glucose sulfate units in DS, up to ~1.5 nmol of monomeric or ~0.75 nmol of dimeric heparin-binding proteins were incorporated without significantly altering the size or zeta potential of the particles. Incorporation efficiencies of these proteins were 95%-100%. In contrast, serum albumin or serum globulin showed minimal incorporation (8% and 4%, respectively) in 50% physiological saline, despite their large adsorption in water (80% and 92%, respectively). The NP-incorporated SDF-1α and VEGF exhibited full activity and sustained thermal stability. An in vivo aerosolization study showed that NP-incorporated SDF-1α persisted in rat lungs for 72 h (~34% remaining), while free SDF-1α was no longer detectable after 16 h. As many growth factors and cytokines contain heparin-binding sites/domains, incorporation into preformed DSCS NPs could facilitate in vivo applications of these proteins.

Mitochondrial transcription factor A contributes to cisplatin resistance in patients with estrogen receptor­positive breast cancer.

Previous studies have reported that triple-negative breast cancer is more sensitive to cytotoxic treatment, compared with estrogen receptor (ER)­positive cancer. However, the underlying molecular mechanisms remain to be fully elucidated. In the present study, we employed reverse transcription­quantitative polymerase chain reaction, western blot and in vivo assays to investigate the underlying mechanisms. The sensitivities of cells to cisplatin were examined in ER-positive and ER­negative breast cancer cells, and it was found that the ER­negative cells were more sensitive to cisplatin, compared with the ER­positive cells. In addition, it was found that mitochondrial transcription factor A (TFAM), which functions in mitochondrial DNA replication and repair, was expressed at a high level in ER­positive cell lines and patient tissues, compared with ER­negative cell lines and tissues. It was also found that the sensitivity to cisplatin was decreased when TFAM was knocked down in the breast cancer cells, and these effects were reversed when TFAM was reintroduced to the cells. Similar results were observed in xenograft tumors. The results of the present study provided evidence that resistance to cisplatin chemotherapy in ER­positive breast cancer may be through TFAM and indicated that TFAM may be a target for chemoresistance in patients with breast cancer. These findings offer potential guidance for chemotherapy in patients with breast cancer.

[Interaction between miR-21 and DNA methylation in different breast cancer cells].

OBJECTIVE: To determine the interaction between miR-21 and DNA methylation in different breast cancer cells. METHODS: Fluorescence tagged miR-21 inhibitor and its negative control (NC) were transient transfected into MCF-7 and MDA-MB-231 cell, the transfection efficiency was observed using fluorescence microscopy, and the miR-21 expression level and genome DNA methylation status before and after transfection were assessed by real-time PCR and bisulfite-qMSP respectively. To investigate the regulation effect of DNA methylation on miR-21, cells were treated with 5-AZA (2.5 µmol/L) for 72 h, with dimethyl sulfoxide (DMSO) treatment as its negative control (NC), and the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and AKT(also known as Protein Kinase B), two downstream genes of miR-21 were detected by Western blot. RESULTS: The expression of miR-21 in MCF-7 cell was significantly knocked down (P < 0.01) by miR-21 inhibitor, with the genome DNA methylation level (P < 0.05) and all the three Dnmts: Dnmt1, Dnmt3a, and Dnmt3b unregulated. In contrast, the miR-21 expression in MDA-MB-231 cell was elevated ( P < 0.01) by miR-21 inhibitor, meanwhile, down- regulated of genome DNA methylation (P < 0.05) and Dnmt3b expression, upregulation of Dnmt3a were also observed. In addition, treated with 5-AZA resulted in significant increases of miR-21 expression in both MCF-7 and MDA-MB-231 cells (P < 0.01), with the protein level of PTEN increased in MCF-7 cell, which was further involved in the downregulation of AKT. CONCLUSION: The regulation effects of DNA methylation by transient transfection of miR-21 in MCF-7 and MDA-MB-231 cells are almost opposite, whilst the expression of miR-21 in two cell lines were all upregulated by decreased DNA methylation level and our results may provide some experimental evidences for the future development of rational therapy for different breast cancer.

Prognostic value of cytokeratin 19 in hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Although many studies have investigated the relationship between cytokeratin 19 (CK-19) and hepatocellular carcinoma (HCC), the prognostic value of CK-19 in HCC remains inconclusive. METHODS: Eligible studies were sought in PubMed, Embase, Web of Science, Cochrane Library and Wanfang databases. Pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. RESULTS: 17 studies with 2943 patients were included in this meta-analysis. Meta-analysis results showed that CK-19 over-expression was significantly associated with overall survival (OS) (HR=1.60, 95% CI: 1.32-1.93, univariate analysis; HR=2.25, 95% CI: 1.79-2.83, multivariate analysis) and disease-free survival (DFS) (HR=1.68, 95% CI: 1.35-2.10, univariate analysis; HR=1.97, 95% CI: 1.54-2.53, multivariate analysis). Meanwhile, CK-19 over-expression was also correlated with decreased 1-year OS rate (OR=0.32, 95% CI: 0.21-0.50), 5-year OS rate (OR=0.44, 95% CI: 0.14-0.87) and 1-year DFS rate (OR=0.51, 95% CI: 0.34-0.76), but not with 5-year DFS rate (OR=0.62, 95% CI: 0.35-1.10). These results suggested that CK-19 over-expression was significantly associated with poor survival rate and early tumor recurrence rate in HCC patients. CONCLUSIONS: CK-19 can serve as an indicator of poor prognosis as well as a novel target for treatment in HCC.

Prognostic and clinicopathological significance of MACC1 expression in hepatocellular carcinoma patients: a meta-analysis.

OBJECTIVE: Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies. However, the prognostic and clinicopathological value of MACC1 in hepatocellular carcinoma (HCC) remains inconclusive. Therefore, we conducted this meta-analysis to investigate the association between MACC1 expression and the outcomes of HCC. METHODS: Relevant articles were searched in PubMed, Embase, Sciencedirect, CNKI, and Wanfang databases updated to October 2014. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were assessed using STATA 10.0, and then the correlations of MACC1 expression with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. RESULTS: 9 studies with a total of 1293 HCC patients were included in this meta-analysis. Our results showed that MACC1 over-expression was significantly associated with poor OS (HR = 2.30, 95% CI 1.47-3.59, univariate analysis; HR = 2.39, 95% CI 1.49-3.82, multivariate analysis), poor DFS (HR = 1.73, 95% CI 1.40-2.13, univariate analysis). Moreover, MACC1 over-expression was significantly associated with AFP level (OR = 1.31, 95% CI 1.03-1.68), tumor number (OR = 1.37, 95% CI 1.07-1.75), differentiation (OR = 2.37, 95% CI 1.46-3.83), TNM stage (OR = 2.89, 95% CI 2.18-3.82), vascular invasion (OR = 1.89, 95% CI 1.43-2.50), capsule invasion (OR = 2.89, 95% CI 1.40-5.94), and metastasis (OR = 2.66, 95% CI 1.16-6.10). CONCLUSION: MACC1 over-expression indicated poor survival rate, high recurrence rate, and aggressive biological behaviors. MACC1 can serve as an indicator of prognosis and a potential novel target for treatment in HCC patients.

Prognostic significance of MMP-7 expression in colorectal cancer: a meta-analysis.

OBJECTIVE: Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix metalloproteinases (MMPs); it is associated with invasive tumor growth and distant metastasis in colorectal cancer (CRC). However, the prognostic value of MMP-7 in CRC remains controversial. Thus, we conducted a meta-analysis to investigate the prognostic value of MMP-7 expression in CRC. METHODS: We systematically searched for studies evaluating the relationship between MMP-7 expression and the outcome of CRC patients in PubMed, the Cochrane library, Embase, Google Scholar, and Wanfang databases updated to August 2014. Studies were assessed for quality using REMARK (REporting recommendations for tumor MARKer prognostic studies). Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were pooled to estimate the hazard for overall survival (OS) and disease-free survival (DFS), and odds ratios (ORs) with 95%CIs were pooled to estimate the impact of MMP-7 on the 5-year survival rate. RESULTS: In total, 2985 patients from 17 studies were included in this meta-analysis. Our results showed that MMP-7 over-expression predicted poor OS (HR=3.57, 95%CI 2.21-5.75, P=0.000, random-effect model), poor DFS (HR=2.49, 95%CI 1.73-3.57, P=0.000, fixed-effect model), and decreased 5-year survival rate (OR=0.26, 95%CI 0.19-0.37, P=0.000, fixed-effect model). Therefore, MMP-7 is an indicator of poor survival and high recurrence rate in CRC patients. CONCLUSION: MMP-7 can serve as a prognostic indicator and a potential novel target for treatment in CRC patients. More well-designed prospective studies with better methodology for MMP-7 assessment are required to clarify the prognostic significance of MMP-7 expression in CRC patients.

Myxoid liposarcoma in the abdominal wall: a case report.

A liposarcoma is the most common type of soft tissue sarcoma, and most liposarcomas are malignant. The extremities are the most common site for liposarcomas. There are 5 histologic types of liposarcoma, as follows: well differentiated; myxoid; round cell; pleomorphic; and dedifferentiated. Myxoid liposarcomas (MLSs) represent a subgroup of liposarcomas. There has been no report of MLSs in the abdominal wall. We report a rare case of a MLS of a 43-year-old male who presented with tensile force on the abdominal wall. Computed tomography (CT) found a tumor in abdominal wall. There was no other abnormal symptom and the laboratory testing was also unusual. At last, the tumor was successfully excised, which was diagnosed MLSs in pathology. Following standard principles, after complete excision, the patient received radiotherapy. The patient was followed up for 8 month and no disease recurrence was identified. MLSs are rarely seen in the clinic, irrespective of the presenting signs, but also based on histologic features. The aim of this report was to present the differential diagnosis of an abdominal wall mass, and to remind us of MLSs.

[Clinical efficacy of tetrandrine combined with acetylcysteine effervescent tablets in treatment of silicosis].

OBJECTIVE: To observe the clinical efficacy of tetrandrine combined with acetylcysteine effervescent tablets in the treatment of silicosis. METHODS: A total of 96 patients with silicosis were randomly divided into treatment group (49 cases) and control group (47 cases). Both groups were given routine therapy including anti-inflammatory, antitussive, and antiasthmatic drugs, and the patients in treatment group were given tetrandrine combined with acetylcysteine effervescent tablets at the same time. Tetrandrine (100 mg) was orally administrated twice a day, and there was a one-day interval between every 6 days' continuous administration; totally, there were four courses of treatment, with 3 months for each course, and there was a one-month break between each course. Acetylcysteine effervescent tablets (600 mg) were taken twice a day; each course of treatment was 12 days, and there were four courses; for the first two months, there was one course per month, and then one course every other two months for the rest of time. Clinical symptoms, pulmonary ventilation function, serum superoxide dismutase (SOD) and changes in X-ray findings were observed. RESULTS: After treatment, the treatment group had significantly increased rates of improvements in cough, expectoration, chest congestion and pain, and dyspnea compared with the control group (P < 0.05). Compared with the control group (serum SOD level: 70.466±20.261 U/ml) and the treatment group before therapy (serum SOD level: 68.182±21.414 U/ml), the treatment group after therapy had significantly increased serum SOD level (77.389±21.315 U/ml?, forced vital capacity, and forced expiratory volume in one second (P < 0.05). Eight patients in treatment group showed improvement in the chest X-ray findings of silicosis. CONCLUSION: The combination of tetrandrine and acetylcysteine effervescent tablets show some effect in the treatment of silicosis. It can be an effective option for treating silicosis as there are no other specific remedies.

Aldosterone inactivates the endothelin-B receptor via a cysteinyl thiol redox switch to decrease pulmonary endothelial nitric oxide levels and modulate pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized, in part, by decreased endothelial nitric oxide (NO(·)) production and elevated levels of endothelin-1. Endothelin-1 is known to stimulate endothelial nitric oxide synthase (eNOS) via the endothelin-B receptor (ET(B)), suggesting that this signaling pathway is perturbed in PAH. Endothelin-1 also stimulates adrenal aldosterone synthesis; in systemic blood vessels, hyperaldosteronism induces vascular dysfunction by increasing endothelial reactive oxygen species generation and decreasing NO(·) levels. We hypothesized that aldosterone modulates PAH by disrupting ET(B)-eNOS signaling through a mechanism involving increased pulmonary endothelial oxidant stress. METHODS AND RESULTS: In rats with PAH, elevated endothelin-1 levels were associated with elevated aldosterone levels in plasma and lung tissue and decreased lung NO(·) metabolites in the absence of left-sided heart failure. In human pulmonary artery endothelial cells, endothelin-1 increased aldosterone levels via peroxisome proliferator-activated receptor gamma coactivator-1α/steroidogenesis factor-1-dependent upregulation of aldosterone synthase. Aldosterone also increased reactive oxygen species production, which oxidatively modified cysteinyl thiols in the eNOS-activating region of ET(B) to decrease endothelin-1-stimulated eNOS activity. Substitution of ET(B)-Cys405 with alanine improved ET(B)-dependent NO(·) synthesis under conditions of oxidant stress, confirming that Cys405 is a redox-sensitive thiol that is necessary for ET(B)-eNOS signaling. In human pulmonary artery endothelial cells, mineralocorticoid receptor antagonism with spironolactone decreased aldosterone-mediated reactive oxygen species generation and restored ET(B)-dependent NO(·) production. Spironolactone or eplerenone prevented or reversed pulmonary vascular remodeling and improved cardiopulmonary hemodynamics in 2 animal models of PAH in vivo. CONCLUSIONS: Our findings demonstrate that aldosterone modulates an ET(B) cysteinyl thiol redox switch to decrease pulmonary endothelium-derived NO(·) and promote PAH.

XPD Asp312Asn polymorphism is a risk factor for prostate cancer.

PURPOSE: The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed. METHODS: An extensive search was performed to identify all case-control studies investigating such association. The strength of association between these two polymorphisms and prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). RESULTS: A total of seven case-control studies were identified, among which five studies (1,257 cases and 1,956 controls) were eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375 controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was associated with an increased risk of prostate cancer in additive and recessive genetic models (additive model: OR = 1.68, 95 % CI = 1.28-2.22, P = 0.00; recessive model: OR = 1.65, 95 % CI = 1.27-2.15, P = 0.00). In the subgroup analysis, Asp312Asn polymorphism was associated with an increased risk of prostate cancer among Asians in all three genetic models (additive model: OR = 2.09, 95 % CI = 1.39-3.14, P = 0.00; dominant model: OR = 1.49, 95 % CI = 1.12-1.98, P = 0.01; recessive model: OR = 1.93, 95 % CI = 1.31-2.83, P = 0.00). However, no significant associations were found between Lys751Gln polymorphism and prostate cancer risk in the overall analyses or the subgroup analyses by ethnicity. CONCLUSIONS: The results of this meta-analysis indicate that the XPD Asp312Asn polymorphism is a risk factor for prostate cancer development.