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Background The aim of this study was to estimate the efficacy and safety of bevacizumab combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non‐small cell lung cancer (NSCLC) patients. Methods We searched randomized controlled trials (RCTs) on bevacizumab combined with EGFR TKIs in the NSCLC Cochrane Library, Web of Science, PubMed and Embase. The data were extracted and assessed according to the Cochrane Handbook. We calculated the hazard ratio (HR), risk ratio (RR), and confidence interval (CI), and accomplished this meta‐analysis with Stata 14 software. Results Of 1301 articles scanned, five articles were involved in this meta‐analysis. We determined that compared with using EGFR TKIs alone, combination treatment significantly prolongs progression‐free survival (PFS) (HR = 0.61, 95% CI = 0.52–0.70; p

Preimplantation genetic diagnosis (PGD) uses molecular biological techniques to genetically diagnose embryos before in vitro fertilization. The information obtained through PGD can help clinicians select healthy embryos for implantation, prevent the transmission of inherited diseases and help affected families have healthy children. This paper reviews the development of PGD technology, the history of its application to hereditary hearing loss, and the general process of how PGD is applied to screen for hereditary hearing loss. The aim of this review is to demonstrate the reliability of PGD in the primary prevention of hereditary hearing loss, assist clinicians in counseling patients at risk of transmitting an inherited disease, and explore the journey from PGD to in vitro fertilization. Given that the application of PGD technology to hereditary hearing loss varies in different countries and regions, there is still a long way to go before PGD is routinely applied for the primary prevention of hereditary hearing loss.

AIM Currently, little studies focus on treatment strategies and survival after progression of gefitinib in older patients with epidermal growth factor receptor )EGFR( mutant advanced non-small-cell lung cancer (NSCLC). The aim of this study was to investigate the influence of different treatment modalities on survival after progression of gefitinib in older patients. METHODS This is a retrospective analysis included 62 consecutively recruited EGFR-mutant advanced NSCLC patients aged over 70 years who failed first-line gefitinib between 2008 and 2018. Kaplan-Meier method was used to estimate curves for overall survival (OS). Multivariate analysis identified independent prognostic risk factors of OS. RESULTS The median age at diagnosis was 75 years (range, 70-88 years). The median progression-free survival of gefitinib was 11.0 months. Forty-four (69.4%) patients continued gefitinib beyond progressive disease (PD), and median gefitinib treatment duration was 18.0 months. Only 67.7% patients received anticancer treatments after discontinuation of gefitinib. The median OS was 24.5 months (95% confidence interval [CI], 19.7-29.3 months). After failure of gefitinib, the osimertinib only group had significantly improved OS compared with chemotherapy or palliative care only groups (37.5 versus 17.5 and 15.3 months, respectively; P = .017). Multivariate analysis showed that continuous gefitinib after Response Evaluation Criteria in Solid Tumor-defined PD (hazards ratio [HR] 0.273, 95% CI: 0.132-0.564, P

In this study, the potential effects of a novel alkali-soluble polysaccharide (ASPP) from purple sweet potato on colonic histopathology, inflammation and microbiota composition in dextran sulfate sodium (DSS)-induced colitis mice were evaluated. The results indicated that ASPP restored the immune organ indices, increased colon length, improved colonic histopathology in colitis mice as well as inhibited the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in colonic tissue and serum. Moreover, 16S rRNA phylogenetic sequencing revealed that ASPP ameliorated the compositions and functions of gut microbiota in DSS-induced colitis mice. It was found that Parasutterella, Desulfovibrio, Lachnospiraceae, Lactobacillus, Erysipelotrichaceae, Bacteroidetes were the key bacteria associated with ulcerative colitis (UC). Taken together, ASPP alleviated colonic inflammation via blocking pro-inflammatory cytokines; meanwhile ASPP could modulate the structure of gut microbiota in DSS-induced colitis mice.

Background Epidermal growth factor receptor (EGFR) gene mutation status is essential to the optimal management of lung adenocarcinoma. Liquid biopsy has advantages such as noninvasiveness, speediness, and convenience. This study aimed to detect EGFR gene mutations using next‐generation sequencing (NGS) from different types of body fluids from patients with lung adenocarcinoma. Methods This was a prospective study of 20 patients with lung adenocarcinoma recruited between January 2017 and December 2018 at the Beijing Hospital. All patients had adenocarcinoma with confirmed sensitizing EGFR mutations. Body fluid specimens included pleural effusion, ascites, pericardial effusion, and cerebrospinal fluid. NGS was conducted to test for nine lung cancer‐related gene in body fluid supernatant free DNA, sedimentary tumor cells, and plasma free DNA. Results The EGFR gene mutation abundance of body fluid supernatant free DNA was higher than that of body fluid sedimentary tumor cells and plasma free DNA specimens (100% vs. 90% vs. 80%, respectively, all P

In this study, the purified water-soluble polysaccharide (ALP-1) from Arctium lappa was used to intervene lipopolysaccharide-induced RAW264.7 macrophage and systemic inflammatory mice. Our results showed that ALP-1 could effectively accommodate the levels of inflammatory cytokines in macrophages and serum of mice, including increased anti-inflammatory cytokine (interleukin-10) and down-regulated pro-inflammatory cytokines (interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α). Moreover, according to our data from 16 s high-throughput sequencing, as compared with LPS model group, the composition of gut microbiota in mice was ameliorated in ALP-1 treatment group. There were higher levels of several probiotics in the stools of ALP-1 treatment group, such as Lactobacillius, Alistipes, Odoribacter, and Phascolarctobacterium. Simultaneously, symbiotic bacteria like Bacteroides were inhibited by ALP-1. Besides, ALP-1 could significantly enhance the production of short chain fatty acids (SCFAs) in gut.

In this study, water-soluble polysaccharide from Arctium lappa was extracted, isolated and purified to be a fraction (ALP-1). Characterization of structure revealed that ALP-1 was a kind of fructan with a molecular weight of 5.12 × 103 Da. ALP-1 was composed of (2→ 1)-β-d-fructofuranose backbone linked to a terminal of (2 → 1)-α-d-glucopyranose at the non-reducing end and a (2 → 6)-β-d-fructofuranose branching. DSS-induced colitis mice were used to determine the inhibitory effects of ALP-1 on gut inflammation. Results indicated that ALP-1 could significantly ameliorate the dysregulation of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and anti-inflammatory cytokine (IL-10) caused by colitis. Besides, as compared with model group, the abundance of Firmicutes, Ruminococcaceae, Lachnospiraceae and Lactobacillus were significantly increased with ALP-1 treatment. And ALP-1 could significantly inhibit the levels of Proteobacteria, Alcaligenaceae, Staphylococcusand and Bacteroidetes. Therefore, ALP-1 may be effective in protecting mice from DSS-induced colitis.

In this study, the ameliorative effect of purified polyphenols from Arctium lappa L (ALPP) on doxorubicin (DOX)-induce heart failure was investigated. Results indicated that ALPP pretreatment significantly reduced the activities of casein kinase and lactate dehydrogenase, lowered the levels of inflammatory indexes (TNF-α and NO), and alleviated antioxidant stress in DOX-induce mice, thus leading to a reduced heart failure syndrome. In addition, according to 16s high-throughput sequencing, the increased abundance of Lactobacillaceae, Muribaculaceae, and Ruminococcaceae and the decreased abundance of Proteobacteria, Enterobacteriaee, and Escherichia_Shigella were observed in ALPP treatment group. ALPP could significantly enhance the abundance of bacteria producing short chain fatty acids (SCFAs) and then promote the increase of SCFAs. Consequently, ALPP might be a therapeutic alternative in the treatment of DOX-induced heart failure. PRACTICAL APPLICATIONS: The effect of Arctium lappa L (ALPP) on doxorubicin (DOX)-induced heart failure was investigated. It provided experimental basis for further studies on the biological activity of polyphenols from ALPP. The results demonstrated that ALPP could significantly ameliorate DOX-induced heart failure and improve the gut microbiota composition. The obtained results could provide the potential application of ALPP as an alternative therapy for heart failure in the functional food industry.

Hereditary hearing loss (HL) has high genetic and phenotypical heterogeneity including the overlapping and variable phenotypic features. For sporadic HL without a family history, it is more difficult to indicate the contribution of genetic factors to define a pattern of inheritance. We assessed the contribution of genetic variants and patterns of inheritance by a family trio-based sequencing and provided new insight into genetics. We conducted an analysis of data from unrelated sporadic patients with HL (n = 404) who underwent trio-based whole-exome sequencing (trio-WES) or proband-only WES (p-WES) or targeted exome sequencing (TES), and the samples of their unaffected-parents (n = 808)were validated. A molecular diagnosis was rendered for 191 of 404 sporadic HL patients (47.3%) in multiple modes of inheritance, including autosomal recessive (AR), autosomal dominant (AD) caused by de novo variants, copy-number variants (CNVs), X-linked recessive, and dual genetic diagnosis. Among these patients, 83 (43.5%) cases were diagnosed with variants in rare genes. Sporadic HL patients were identified by multiple modes of transmission. Observed variations in rare genes and multiple modes of inheritance can strikingly emphasize the important etiological contribution of recessive and de novo genetic variants to a large cohort of sporadic HL cases plus their parents.

The geriatric nutritional risk index (GNRI) is a simplified nutritional assessment. This study aimed to evaluate the prognostic value of the pretreatment GNRI in geriatric patients with metastatic lung adenocarcinoma (MLA). The clinicopathological characteristics of 144 geriatric patients with MLA were analyzed. The receiver operating characteristic curve was used to determine the best cutoff value of GNRI for predicting overall survival (OS). The Cox regression was used to identify variables associated with OS in the whole group, the non-sensitizing

BACKGROUND Lead (Pb) is a widely used metal in modern industry and is regarded as a health hazard. Although lead-induced genotoxicity has been confirmed, the direct evidence that lead induces genotoxicity in human cells and its related mechanisms has not been fully elucidated. In this study, for the first time, we evaluated the genotoxicity induced by lead in human lymphoblastoid TK6 cells. MATERIAL AND METHODS The TK6 cells were incubated with various concentrations of Pb(Ac)2 for 6 h, 12 h, or 24 h. Cell viability was detected by CCK8 assay. Various biochemical markers were assessed by specific kits. Immunofluorescence assay was used to detect g-H2AX foci formation. The promoter methylation was assessed by methylation-specific PCR. The protein levels were determined by Western blot assay. RESULTS The results showed that after exposure to lead, cell viability was obviously decreased and γ-H2AX foci formation was significantly enhanced in TK6 cells. Moreover, the levels of 8-OHdG, ROS, MDA, and GSSG were increased, while the GSH level and SOD activity were decreased in lead-treated TK6 cells. The activation of the Nrf2-ARE signaling pathway was involved in lead-induced oxidative stress in TK6 cells. Finally, the expressions of DNA repair genes XRCC1, hOGG-1, BRCA1, and XPD were inhibited via enhancing their promoter methylation in TK6 cells after exposure to lead. CONCLUSIONS Taken together, our study provides the first published evidence that lead exposure results in DNA damage via promoting oxidative stress and the promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells.

Xenon/krypton (Xe/Kr) separation is of industrial importance. Environmental concerns exist for pure noble-gas production and the reprocessing of noble-gas radioisotopes from used nuclear fuel. Cryogenic distillation as the main technology for Xe/Kr separation is energy and capital intensive. Thus, the development of a more economical and energy-efficient alternative, such as adsorptive separation based on solid porous materials, is urgent and significant. Herein, we prepared metal–organic-framework derived nanoporous carbons as new promising porous materials for highly selective Xe/Kr separation. A series of metal–organic-framework (MOF) derived nanoporous carbons (Z11CB-700, Z11CB-800, Z11CB-900, Z11CB-1000, Z11CB-1100, Z11CBF-1000-1, Z11CBF-1000-2 and Z11CBF-1000-3) were synthesized with ZIF-11 ([Zn(bIM)2], HbIM = benziminazole) as a precursor and furfuryl alcohol as an optional carbon source. A systematic investigation of the Xe/Kr separation was performed on these nanoporous carbons, and they were compared with commercial activated carbon. Z11CBF-1000-2 shows significantly high Xe Henry coefficient (80.01 mmol g−1 bar−1) and high thermodynamic Xe/Kr selectivity (19.7) at very low partial pressures relevant to nuclear-fuel reprocessing. Single-column breakthrough experiments indicate that the Z11CBF-1000-2 exhibits benchmark Xe capacity (20.6 mmol kg−1) under dynamic dilute conditions, which implies its promising potential to capture and separate Xe in used nuclear-fuel reprocessing facilities.

Background: Immunotherapy can induce a long response in part patients of lung squamous cell carcinoma (LUSC). And accurate biomarkers are needed for suitable populations. As important tumor suppressor, tumor protein p53 (TP53) and low density lipoprotein receptor-related protein 1B (LRP1B) genes may be associated with immunogenicity. However, the interaction of TP53 and LRP1B and its potential association with response to immunotherapy are not fully understood in LUSC. Methods: Three cohorts were divided into four groups, respectively (A: TP53mut and LRP1Bmut, B: TP53mut and LRP1Bwild, C: TP53wild and LRP1Bmut, D: TP53wild and LRP1Bwild). 525 LUSCs form Geneplus database which performed next-generation sequencing were assessed the differences of genomic landscape, tumor mutation burden (TMB), and PD-L1 expression in four groups (cohort 1). TCGA-LUSC RNA data (n=466) from cBioPortal were used to evaluate immune cell infiltration thought single sample gene set enrichment analysis (cohort 2). The LUSCs (n=125) which received immunotherapy of POPLAR and OAK cohort were used to evaluate the efficacy of immunotherapy in four groups (cohort 3). Results: The proportion of patients in A, B, C and D groups of cohort 1 was 26%, 59%, 2%, 13%, respectively, suggesting that most patients with LRP1B mutation also carry TP53 mutation (98.6%) in LUSC. This similar ratio is 88.2% in cohort 2 and 74.3% in cohort 3. For group A, the most common mutated gene except TP53 and LRP1B was CDKN2A (31%). Group B was MLL2(28%). Group C was CDKN2A (33%). Group D was FAT1 (13%). The median TMB was 14.4 mutations/Mb (2.9-80.0) in group A, 9.8 (0.96-95.0) in group B, 11.5 (2-25) in group C, 3.8 (0.96-18.2) in group D. TP53 and LRP1B co-mutation had a highest TMB compared with the other three groups in all cohorts, while TP53wild and LRP1Bwild completely opposite. In cohort 1, PD-L1 expression had no significant difference in four groups. In cohort 3, progression-free survival (PFS) was longer in group D compared with the other three groups (p = 0.047, A: 1.5m, B: 1.6m, C: 2.1m, D: 4.2m). The same trend on overall survival (OS) were found but it was not significant. Group D also had a higher disease control rate (A: 50%, B: 46%, C: 44%, D: 69%). We than divide into two groups (D vs Other) to compare PFS and OS. It showed that group D had a prolonged PFS (p = 0.02) and OS (p = 0.03). Multivariate cox regression analysis showed that the results were independent of TMB, gender and age. Analysis of immune cell infiltration in cohort 2 showed that the better outcomes of group D might associated with elevated infiltrations of activated dendritic cell and activated CD8 T cell. Conclusion: TP53mut and LRP1Bmut, which accounted for a high proportion of LUSC, was associated with high TMB. And TP53wild and LRP1Bwild has better anti-PD-L1 outcome in LUSC. This might be related with a stronger activated dendritic cell and activated CD8 T cell infiltration despite lower TMB. Citation Format: Jiangyong Yu, Zhipeng Zhou, Ping Zhang, Pansong Li, Xu Li, Min Tang, Nannan Fan, Xiaonan Wu, Xin Nie, Xiaoyan Chen, Di Ma, Xi Chen, Yanfang Guan, Xuefeng Xia, Ling Yang, Xin Yi, Lin Li. Association of TP53 and LRP1B co-mutation status with response to immunotherapy in lung squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2492.

Background Lung cancer is the most malignant tumor with the highest morbidity and mortality. This study aimed to investigate the role of the expression and the significance of the p42.3 gene in non-small cell lung cancer (NSCLC). Methods Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed based on the biological information data of The Cancer Genome Atlas (TCGA). Furthermore, 142 postoperative tumor tissue and normal tissue samples (70 cases of LUAD and 72 cases of LUSC) from NSCLC patients admitted to our hospital from 2005 to 2009 were retrospectively collected. Paraffin-embedded tissues were used to make the tissue microarrays (TMA), and the expression of the p42.3 protein was detected by immunohistochemical staining. Results The expression of p42.3 in both LUAD and LUSC was significantly upregulated (P

Objective The relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. Methods Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded. Results Of the 313 MPE samples, 27 (8.6%) were confirmed as ALK expression-positive, and the Ventana IHC ALK (D5F3)-positive rate was 17.3% (27/156) in wild-type epidermal growth factor receptor (EGFR) MPE samples. Twenty-three of the 27 IHC ALK (D5F3)-positive samples were positive by FISH. Of the 11 Ventana IHC ALK (D5F3)-positive patients who received crizotinib therapy, 2 patients had complete response (CR), 5 had partial response (PR) and 3 had stable disease (SD). Conclusions The ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.

Aim: To evaluate the Ventana IHC ALK (D5F3) assay for detecting anaplastic lymphoma kinase (ALK) protein expression in pleural effusion samples. Methods: Historical, selected (wild-type EGFR, K-RAS) pleural effusion cytologic blocks of lung adenocarcinoma samples (Study 1) and unselected lung adenocarcinoma pleural effusion cytologic blocks (Study 2) were tested by Ventana IHC ALK (D5F3) assay. Quantitative real-time-PCR was used to verify immunohistochemistry results. Results: A total of 17 out of 100 (Study 1) and ten out of 104 (Study 2) pleural effusion samples were ALK expression positive by the Ventana IHC ALK (D5F3) assay. The ALK fusion results with immunohistochemistry and quantitative real-time-PCR had a concordance rate of 87.5% (κ = 0.886; p < 0.001). Conclusion: The Ventana IHC ALK (D5F3) assay is a reliable tool for detecting ALK protein expression in pleural effusion samples.

We evaluated the efficiency of transfecting adenoviral vectors encoding enhanced green fluorescent protein (AdCMV-EGFP) into rat submandibular gland cells and the effects of gene transfer on cell proliferation and secretory function. Isolated submandibular gland cells were transfected with different titers (or multiplicity of infection, MOI) of AdCMV-EGFP. The transfection efficiency was evaluated by quantifying EGFP-positive cells by inverted fluorescence microscopy, cell proliferation by MTT assay, and cell secretory activity by measuring α-amylase in culture medium. A transfection efficiency of up to 70.8 % was achieved in submandibular gland cells. MTT assay showed that increased viral titers resulted in significant inhibition of cell proliferation, which occurs on day 5 post-transfection. Simultaneously, the amylase levels started to reduce with a significant decrease on day 7 after transfection. The results show that AdCMV-EGFP transfection of submandibular gland cells at higher MOI results in cytotoxicity, decreased cell proliferation, and secretory function. However, the lower adenoviral titers (e.g., 200 particles/cell) could be an efficient and safe labeling tool for gene transfer to submandibular gland cells.

e24328Background: Apatinib is an oral, highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2).It can be used alone or combined with other chemother...

Tubular epithelial loss has been shown to be responsible for the formation of atubular glomeruli leading to nephron decomposition and interstitial fibrosis in obstructive uropathy. Cells undergoing apoptosis and autophagic cell death play an important role in this process, yet the mechanisms are not fully understood. In this study, we aimed to investigate whether autophagy cooperating with apoptosis is associated with mitochondrial damage and whether oxidative stress plays an important role in the loss of tubular epithelium following unilateral ureteral obstruction. In this model, we demonstrated that there is coexistence of autophagy and apoptosis with tubular atrophy in obstructed proximal tubules. After unilateral ureteral obstruction (UUO), autophagy in proximal tubular cells was enhanced steadily up to 7 days in the obstructed kidney and declined thereafter, while apoptosis was induced in a time-dependent manner from 3 to 14 days. Mitochondrial structure and number also changed during UUO. Lipid peroxidation products, NOX4, and NADPH oxidase activity were also increased in the obstructed renal cortex, and peaked at 7 days. In vitro, we showed that H2O2 induced mitochondrial injury leading to autophagy and apoptosis through the Beclin 1 pathway and interference with Bcl-2 expression. Thus, our data demonstrate that oxidative stress leading to mitochondrial damage and driven autophagy-dependent cell death and apoptosis are important mechanisms of tubular decomposition in obstructive nephropathy.

Background It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Methods Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. Results MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. Conclusions IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury.

Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of α-smooth muscle actin (α-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of α-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT.

This study was aimed at assessing physicians' and physician assistants' knowledge and attitudes toward HIV/AIDS and identifying determinants of willingness to care for infected individuals in Southeast China. From May to June 2004, 454 physicians and physician assistants from 5 different medical facility levels in Fujian Province, China, undertook a survey on knowledge, attitude, behavior, and practice (KABP). Only 40.4% (95% confidence intervals: 35.9, 44.9) were willing to provide healthcare services for people living with HIV/AIDS (PLWHAs). Knowledge (p0.001) and attitude scores (p = 0.01) as well as the proportion of those willing to provide care (p0.001) significantly differed by facility level. Multivariate analysis identified supportive attitudes toward PLWHAs (p0.001), self-confidence in providing care (p0.001), and facility level as significant predictors of willingness to care for infected individuals. Village medical stations showed the most unfavorable outcomes. Enhanced education as well as specific programs promoting supportive attitudes and willingness to care is therefore required, especially among those working at lower facility levels in remote areas.