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Protein deglycase DJ‐1 (DJ‐1) is a multifunctional protein involved in various biological processes. However, it is unclear whether DJ‐1 influences atherosclerosis development and plaque stability. Accordingly, we evaluated the influence of DJ‐1 deletion on the progression of atherosclerosis and elucidate the underlying mechanisms. We examine the expression of DJ‐1 in atherosclerotic plaques of human and mouse models which showed that DJ‐1 expression was significantly decreased in human plaques compared with that in healthy vessels. Consistent with this, the DJ‐1 levels were persistently reduced in atherosclerotic lesions of ApoE−/− mice with the increasing time fed by western diet. Furthermore, exposure of vascular smooth muscle cells (VSMCs) to oxidized low‐density lipoprotein down‐regulated DJ‐1 in vitro. The canonical markers of plaque stability and VSMC phenotypes were evaluated in vivo and in vitro. DJ‐1 deficiency in Apoe−/− mice promoted the progression of atherosclerosis and exaggerated plaque instability. Moreover, isolated VSMCs from Apoe−/−DJ‐1−/− mice showed lower expression of contractile markers (α‐smooth muscle actin and calponin) and higher expression of synthetic indicators (osteopontin, vimentin and tropoelastin) and Kruppel‐like factor 4 (KLF4) by comparison with Apoe−/−DJ‐1+/+ mice. Furthermore, genetic inhibition of KLF4 counteracted the adverse effects of DJ‐1 deletion. Therefore, our results showed that DJ‐1 deletion caused phenotype switching of VSMCs and exacerbated atherosclerotic plaque instability in a KLF4‐dependent manner.

BACKGROUND Routinely, after receiving prostate specific antigen (PSA) testing and digital rectum examination, patients with suspected prostate cancer are required to undergo prostate biopsy. However, the ability of ultrasound-guided prostate biopsy to detect prostate cancer is limited. Nowadays, a variety of diagnostic methods and more sensitive diagnostic methods, such as multi-parameter prostate magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) can be applied clinically. Furthermore, laparoscopic/robot-assisted prostatectomy is also a safe and effective procedure for the treatment of benign prostatic hyperplasia. So maybe it is time to reconsider the necessary to perform prostate biopsy before radical prostatectomy. AIM To explore the feasibility of radical prostatectomy without prostate biopsy in the era of new imaging technology and minimally invasive techniques. METHODS From June 2014 to November 2018, 11 cases of laparoscopic radical prostatectomy without prostate biopsy were performed at the three tertiary medical centers involved in this study. All patients received prostate magnetic resonance imaging and prostate cancer was suspected, including six patients with positive 68Ga-PSMA PET/CT results. Laparoscopic radical prostatectomy and pelvic lymph node dissection were performed for all patients. RESULTS All surgeries were accomplished successfully. The mean age was 69 ± 7.7 year, the mean body mass index was 24.7 ± 1.6 kg/m2, the range of serum PSA was 4.3 to >1000 ng/mL, and the mean prostate volume was 40.9 ± 18.3 mL. The mean operative time was 96 ± 23.3 min, the mean estimated blood loss was 90 ± 90.9 mL, and the median duration of catheter placement was 14 d. The final pathology confirmed that all specimens were prostate cancer except one case of benign prostatic hyperplasia. No major complications occurred in 90 d postoperatively. CONCLUSION The current practice of mandating a prostatic biopsy before prostatectomy should be reconsidered in the era of new imaging technology and minimally invasive techniques. Radical prostatectomy could be carried out without the evidence of malignancy. Large-sample randomized controlled trials are definitely required to confirm the feasibility of this new concept.

Objective To investigate the clinicopathological features and prognosis of chromophobe renal cell carcinoma(ChRCC). Methods The clinical and pathological data of 126 patients with ChRCC treated in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Results The patients included 64 males and 62 females,with the age of 22-80 years(median of 52 years).The tumor was located on the right side in 70 cases and on the left side in 56 cases.Ultrasound,CT or magnetic resonance imaging(MRI)were performed.Of the 110 cases receiving ultrasound examination,63,23,13,10,and 1 cases showed hypoecho,hyperecho,isoecho,uneven or mixed echo,and dark hypoecho,respectively.Color Doppler flow imaging showed no blood flow signal in 42 cases and low blood flow signal in 60 cases out of 68 cases with blood flow signal.Among the 54 cases receiving CT,50 cases showed equal density or low density and 4 cases showed high density with clear boundary.The enhanced scanning showed mild to moderate uniform or non-uniform reinforcement,mostly below the renal parenchyma,and still showed reinforcement in the delayed period.Among the 97 cases receiving MRI,96 cases showed hypo-or isointense signals and 1 case showed hyperintense signal in T1 weighted images;71 cases showed hyper-or isointense signals and 26 cases showed hypo-or isointense signals in T2 weighted images;93 cases showed hyperintense signals with obvious limited diffusion and 4 cases showed unobvious limited diffusion in diffusion weighted images.Mild to moderate uniform or non-uniform reinforcement was observed in most of the enhanced scans.All the 126 patients underwent surgical treatment,including 64 cases of nephron sparing surgery and 62 cases of radical surgery.Pathological examinations confirmed ChRCC for all the patients,including 91 cases of T1N0M0,15 cases of T2N0M0,and 20 cases of T3N0M0.The immunohistochemical assay demonstrated the positive expression rate of 48.2%(54/112)for CD10,92.3%(96/104)for CD117,8.0%(9/112)for vimentin,85.6%(95/111)for CK7,and 97.6%(83/85)for colloidal iron.Conclusions ChRCC is less common,with low level of malignancy and good prognosis.Since the clinical symptoms of ChRCC are not typical,MRI is an important means of imaging differential diagnosis,and the disease can be confirmed depending on pathological diagnosis.Surgery is the preferred treatment method,and currently there is no standard treatment regimen for metastatic patients.

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design., Graphical Abstract, Bringing together epidemiological, genetic, and clinical data, Lin et al. identify viral mutations that associate with clinical phenotypes. The 500-532 locus in the Nsp1 coding region is a deletion hotspot in the SARS-CoV-2 genome, and deletion variants lead to lower IFN-I response. Prevalence of 500-532 deletion variants is accumulating worldwide.

Salvianolic acid B (Sal B) is a representative component of phenolic acids derived from the dried root and rhizome ofIn the present study, ischemic stroke models were induced in rats by middle cerebral artery occlusion (MCAO), and Sal B (10 or 20 mg/kg/d) was intraperitoneally injected according to a previous study. Neurological deficits were evaluated by the modified Longa five-point scale, modified Bederson scores and cerebral infarction sizes by triphenyltetrazolium chloride (TTC) staining. Apoptotic cells were tested by cleaved-caspase3 immunofluorescence staining and an in situ cell death (TUNEL) detection kit. Human umbilical vein endothelial cells (HUVECs) exposed to hypoxia were used to investigate the effects of Sal B on angiogenesis and tube formationSal B ameliorated the neurological deficits, decreased the cerebral infarction volumes in rats with ischemic stroke, significantly increased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and VEGFA and promoted angiogenesis bothThis study showed that Sal B promoted angiogenesis and alleviated neurological apoptosis in rats with ischemic stroke by promoting STC1.

Long non‑coding RNAs (lncRNAs) serve key roles in cell growth, development and various diseases associated with the central nervous system. However, differential expression profiles of lncRNAs in type 2 diabetes have not been reported. The present study aimed to analyze the expression pattern of lncRNA‑mRNA in a type 2 diabetic mouse model using microarray analysis. The mouse model of type 2 diabetes was established and the total RNAs were extracted from the hippocampus of the mice used in the present study. The total RNAs were then examined by the GeeDom human lncRNA + mRNA V4.0 expression profile and analyzed through comparing Gene Ontology (GO) enrichment analysis and signal pathway analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. There were statistically significant differences between the expression of IncRNAs and mRNA in the healthy mice and that of the diabetic mice. In the diabetic mice, 130 different lncRNAs were expressed with 126 significantly upregulated and 4 significantly downregulated and 49 different mRNAs were detected with 45 significantly upregulated and 4 downregulated. GO analysis indicated that the mRNAs that are affected are involved in transport, cell adhesion, ion transport and metabolic processes. KEGG and Reactome enrichment analysis indicated that mRNAs impact on cholinergic synapses, nuclear factor‑kB pathway, Toll like receptor 4 cascade and zinc transporter are correlated with cognitive dysfunction in type 2 diabetes. A dynamic lncRNA‑mRNA network was constructed containing 123 lncRNAs and 48 mRNAs, which can elucidate the interaction between lncRNA and mRNA. Overall, this is the first study to indicate that lncRNAs are differentially expressed in the type 2 diabetic mice.

A chemical investigation on the 80% EtOH extract of the aerial parts of Kopsia fruticosa led to five new indole alkaloids, kopsifolines G-K (1–5), and one known alkaloid, kopsifoline A (6). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated components were evaluated in vitro for cytotoxic activities against seven tumor cell lines, antimicrobial activities against two Gram-positive bacteria and five Gram-negative bacteria, and antifungal activities against five pathogens. As a result, alkaloids 3–5 exhibited some cytotoxicity against all of seven tested tumor cell lines (HS-1, HS-4, SCL-1, A431, BGC-823, MCF-7, and W480) with IC50 values of 11.8–13.8, 10.3–12.5, and 7.3–9.5 μM, respectively. Alkaloids 3–5 also possessed significant antimicrobial and antifungal activities which was reported for the first time for the alkaloids isolated from Kopsia genus.

Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anti‑cancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the under‑reported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The anti‑proliferative and pro‑apoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit‑8 and Annexin V‑fluorescein isothiocyanate/propidium iodide assays. Cell scratch‑wound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)‑2 and ‑9 in a concentration‑dependent manner, which may support a novel potential mechanism accounting for its anti‑cancer effects on gastric cancer.

This paper demonstrates cooling of the center-of-mass motion of 10 $\mu$m-diameter optically levitated silica spheres to an effective temperature of $50\pm22 \mu$K, achieved by minimizing the technical pointing noise of the trapping laser. This low noise leads to an acceleration and force sensitivity of $95\pm41$ n$g/\sqrt{\mathrm{Hz}}$ ($g = 9.8$ m/s$^2$) and $0.95\pm0.11$ aN$/\sqrt{\mathrm{Hz}}$, respectively, at frequencies near 50 Hz. This force sensitivity is comparable to that demonstrated for optically levitated nanospheres that are $10^4$ times less massive, corresponding to an acceleration sensitivity that is several orders of magnitude better. It is further shown that under these conditions the spheres remain stably trapped at pressures of $\sim 10^{-7}$ mbar with no active cooling for periods longer than a day. Feedback cooling is still necessary in the moderate-pressure regime, motivating a comprehensive study of the loss mechanisms of the microspheres and providing better understanding of the requirements for feedback-free optical trapping in vacuum. This work can enable high-sensitivity searches for accelerations and forces acting on micron-sized masses, including those that could be produced by new physics beyond the Standard Model.

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.

Background Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. Methods Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. Results Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia . Conclusions Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.

Objective The aim of this study was to summarize the current evidence to evaluate the effects of laparoscopic radical nephrectomy (LRN) and open radical nephrectomy (ORN) in the treatment of renal cell carcinoma. Methods A comprehensive literature search was performed using PubMed, Embase and Google Scholar to identify all relevant studies. 8 published studies were included in this meta-analysis. We pooled the odds ratios (OR), standardised mean difference (SMD) and conducted heterogeneity, and quality assessment. Results The outcome of treatment effects included surgical blood loss, surgical time, postoperative complications, and post-operative length of hospital stay. Comparing open radical nephrectomy for kidney cancer patients, the pooled SMD of surgical time was 0.47, (95% confidential index CI = [0.09, 0.85]), the pooled SMD of operative blood loss was -68.98, (95% CI = [-99.63, -38.34]), the pooled SMD of post-operative length of hospital stay was -4.32, (95% CI = [-4.62, -4.03]), and the pooled OR of postoperative complications was 0.52, (95% CI = [0.30, 0.91]). Conclusion LRN was found to significantly decrease patients’ blood loss. In addition, LRN offers less post-operative length of hospital stay.

To identify genetic susceptibility genes and the loci of their single nucleotide polymorphisms (SNPs) in patients with testicular germ cell tumor (TGCT) and provide some new ideas for the prediction, diagnosis and treatment of TGCT.We identified 41 SNP loci of TGCT-related genetic susceptibility genes from the literature published abroad. Using the iMLDRTM genotyping technique, we examined the SNP loci of the genetic susceptibility genes in the blood samples from 76 TGCT patients (aged 16－68 years) and 148 healthy men (aged 22－61 years) in China and analyzed their correlation with TGCT.In China, TGCT was found to be correlated with the SNP loci rs2978381, rs10146204, rs12435857 and rs1256063 of the ESR2 gene, rs9397080 of the ESR1 gene, rs11202586 of the PTEN gene, rs2606345 and rs4646903 of the CYP1A1 gene, and rs1456432 of the CYP19A1 gene.The results of our study indicated some difference in the positive SNP loci of the TGCT patients between Chinese and foreign cohorts as well as in different groups in China.目的： 通过对76例睾丸生殖细胞肿瘤(TGCTs)患者与148例健康体检人群41个相关基因单核苷酸多态性（SNPs）位点进行病例对照研究，期望发现国内TGCTs患者的遗传易感基因及位点，为临床预测、诊治TGCTs提供新途径。方法： 选取国外文献发现的TGCTs患者易感基因的41个SNPs位点，作为本实验待测位点。采用iMLDRTM 分析方法，将76例TGCTs患者及148例健康体检人群血液样本进行待测位点分型检测。结果： 在我国，ESR2基因的rs2978381、rs10146204、rs12435857、rs1256063位点， ESR1基因的rs9397080位点，PTEN基因的rs11202586位点，CYP1A1基因的rs2606345、rs4646903位点和CYP19A1基因的rs1456432 位点与TGCTs相关。结论： 本研究中TGCTs患者的相关SNPs位点与国外TGCTs人群存在差异，国内TGCTs患者的相关SNPs位点也不完全相同。

Short-term power load forecasting is an important basis for the operation of integrated energy system, and the accuracy of load forecasting directly affects the economy of system operation. To improve the forecasting accuracy, this paper proposes a load forecasting system based on wavelet least square support vector machine and sperm whale algorithm. Firstly, the methods of discrete wavelet transform and inconsistency rate model (DWT-IR) are used to select the optimal features, which aims to reduce the redundancy of input vectors. Secondly, the kernel function of least square support vector machine LSSVM is replaced by wavelet kernel function for improving the nonlinear mapping ability of LSSVM. Lastly, the parameters of W-LSSVM are optimized by sperm whale algorithm, and the short-term load forecasting method of W-LSSVM-SWA is established. Additionally, the example verification results show that the proposed model outperforms other alternative methods and has a strong effectiveness and feasibility in short-term power load forecasting.

The key technology of the auto parts management system based on the Internet of things, to realize the system function and the pre-objectives of the information management, through the construction the software part of the whole system, and the hardware of completing the information collection and transmission. Not only to save storage time-consuming, but also to avoid the emergence of errors, as compared to the traditional hand-held terminal, its identification efficiency has been improved. After RFID identification, the auto parts directly enter into the system, the efficiency has been improved than the traditional way, while the indicator on the shelves reminds effectively synchronously, improve the recognition accuracy and efficiency of labor.

Although many of the first-generation Digital Earth systems have proven to be quite useful for the modeling and visualization of geospatial objects relevant to the Earth’s surface and near-surface, they were not designed for the purpose of modeling and application in geological or atmospheric space. There is a pressing need for a new Digital Earth system that can process geospatial information with full dimensionality. In this paper, we present a new Digital Earth system, termed SolidEarth, as an alternative virtual globe for the modeling and visualization of the whole Earth space including its surface, interior, and exterior space. SolidEarth consists of four functional components: modeling in geographical space, modeling in geological space, modeling in atmospheric space, and, integrated visualization and analysis. SolidEarth has a comprehensive treatment to the third spatial dimension and a series of sophisticated 3D spatial analysis functions. Therefore, it is well-suited to the volumetric representation and visual analysis of the inner/ outer spheres in Earth space. SolidEarth can be used in a number of fields such as geoscience research and education, the construction of Digital Earth applications, and other professional practices of Earth science.

3D geological modeling is becoming ubiquitous in the visualization and analysis of the subsurface geological characterization that involves both geometrical structure and various properties. The engineering geological space consists of two types of data fields: one is the geological structure field and the other is the property parameter field. There are two kinds of relationships, i.e. superposition and coupling, between property parameter fields and geological structure fields. While many of the current modeling techniques have proven to be quite useful for modeling and visualization of geological structures or property parameters independently, they were never designed for the purpose of handling the coupling relationship among different data fields. This shortcoming seriously limits the reliability and practicality of the computer models, and there is a pressing need to build a meaningful 3D spatial model that involves both geometry and properties. In this paper, we present a novel modeling framework for the coupled modeling and analysis of geo-objects in 3D engineering geological space. There are three innovative improvements in this framework. First, a mixed 3D spatial data model, which is a combination of boundary representation and Geocellular, is designed to address the need for the unified description of geometry and topology of geo-objects as well as their internal properties. And then, in order to obtain geologically reasonable property models controlled by geological constraints, the qualitative geological constraints are converted into quantitative control parameters in data preprocessing stage, and different property interpolation schemes are used respectively to handle different types of geo-objects. And finally, in order to gradually refine 3D geological models, the iterative modeling technique is imported, and an efficient mechanism for information feedback and error correction is set up. This coupled modeling framework is well-suited to produce detailed 3D geological models attributed with physical, chemical, engineering or hydrogeological parameters, and intuitively analyze property characteristics within each modeled unit and their spatial relationships in 3D.

Tuberous sclerosis complex 1 (TSC1) and TSC2 are suppressors of mechanistic target of rapamycin (mTOR). mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2. Inactive mutation of either TSC1 or TSC2 unleashes mTOR signaling and consequently causes TSC, a benign tumor syndrome affecting multiple organs. We report here that expression of αB-crystallin was upregulated in Tsc1-/- or Tsc2-/- mouse embryonic fibroblasts, Eker rat uterine leiomyoma-derived Tsc2-deficient ELT3 cells, mutant Tsc2-associated mouse kidney tumors, and human lung lymphangioleiomyomatosis nodules. αB-crystallin was transcriptionally activated by mTOR complex 2 (mTORC2): nuclear factor-kappa B (NFκB) signaling cascade. The augmented αB-crystallin was critical for the migration, invasion and apoptotic resistance of Tsc2-defective cells. Disruption of αB-crystallin suppressed Tsc2-null cell proliferation and tumorigenesis. Therefore, enhanced αB-crystallin has an essential role in TSC1/2 complex deficiency-mediated tumorigenesis, and inhibition of αB-crystallin may complement the current therapy for TSC.

Hydroxysafflor yellow A (HSYA), is a component of the flower, Carthamus tinctorius L. In this study, we investigated its effect on Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia. We evaluated cell viability using the MTT kit. The cell cycle distribution was analyzed by PI staining flow cytometric analysis. PI AnnexinV-FITC detection and the TUNEL assay were performed to evaluate the apoptosis rate. Nitric oxide (NO) generation in cell supernatant was measured by the Griess assay. RT-PCR, Western blot and Immunocytochemistry analysis were used to evaluate the changes of Bcl-2, Bax, p53 and eNOS. Our data showed that HSYA inhibited cell apoptosis and cell cycle G1 arrest induced by hypoxia. HSYA treatment increased the Bcl-2/Bax ratio of protein and mRNA, reduced p53 protein expression in cell nucleus. In addition, HSYA enhanced the NO content of cell supernatant under hypoxia, accompanied with upregulating eNOS mRNA expression and protein level. Taken together, these results demonstrate that HSYA could protect HUVECs from hypoxia induced injuries by inhibiting cell apoptosis and cell cycle arrest. These findings have partly revealed the molecular mechanism of HSYA on treating of ischemic heart disease. We expected our experiments might provide some clues for further research.

This experiment studied the effect of Cordyceps sinensis extract (CSE) on mice aged by d-galactose and castrated rats to analyse its antiaging effect. Water maze and step-down type avoidance tests were used to examine the effect of CSE on learning and memory. CSE shortened escape latency, prolonged step-down latency and decreased the number of errors in mice aged by d-galactose. The effect of CSE on the sexual function of castrated rats was evaluated by measuring the penis erection latency, mount latency and ejaculation latency. CSE appeared to shorten penis erection latency and mount latency in castrated rats. The study also measured the effect of CSE on the activity of age-related enzymes. The results showed that CSE improved the activity of superoxide dismutase, glutathione peroxidase and catalase and lowered the level of lipid peroxidation and monoamine oxidase activity in the aged mice. The study demonstrated that CSE can improve the brain function and antioxidative enzyme activity in mice with d-galactose-induced senescence and promote sexual function in castrated rats. All of these findings suggest that CSE has an antiaging effect.

In this study, we established a drug screening system based on transcriptional regulation of vascular endothelial growth factor (VEGF) under hypoxia-inducible factor-1alpha control. We cloned the neomycin-resistance gene into the plasmid GL (pGL)3-promoter vector to generate the pGL3-promoter-neo vector. The 3 copies of the 47-bp fragment that contained the hypoxia response element of VEGF were synthesized and inserted in front of the minimal promoter of the pGL3-promoter-neo vector to generate p3HRE-luc-neo. The recombinant reporter gene vectors were transfected into EAhy926 cells, and stable cell lines were obtained. The positive cell line was selected for its ability to express luciferase in response to hypoxia. We demonstrated that CoCl(2) significantly enhances luciferase activity in a concentration-dependent fashion. We then optimized the cell density and incubation time under hypoxia which were used to screen. The assay exhibited a low background and was an ideal model for high-throughput screening for human VEGF regulators.

Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.

The compound LXM-10 (2,4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro [5.5]undecane chloride) is a new spirocyclopiperazinium salt compound. This is the first article to evaluate its antinociceptive effect in the abdominal constriction test induced by acetic acid and the hot-plate test. In the abdominal constriction test, LXM-10 had a significant dose-response effect, and the maximal inhibition ratio was 79.2%. In the hot-plate test, LXM-10 had significant dose-response and time-response effects. The antinociceptive effect began at 1.0 h, peaked at 2.0 h, and persisted 3.0 h after s.c. administration. The hot-plate latency was increased by 126.8% at the dose of 12.0 mg/kg. The antinociceptive effect of LXM-10 was blocked by mecamylamine (a central and peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.25, 0.5, 1.0 mg/kg, i.p.), hexamethonium (a peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), atropine (a central and peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), and atropine methylnitrate (a peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.) in a dose-dependent fashion. In contrast, the effect was not blocked by naloxone (a non-selective opioid receptor antagonist, 2.0 mg/kg, i.p.) or yohimbine (a alpha(2)-adrenergic receptor antagonist, 1.0, 2.5, 5.0 mg/kg, i.p.) in the hot-plate test. Therefore, the antinociceptive effects of LXM-10 involve the peripheral neuronal nicotinic and muscarinic acetylcholine receptors; they are not related to opioid receptors or alpha(2)-adrenergic receptors. LXM-10 did not affect motor coordination, spontaneous activity, or body temperature. These findings with LXM-10 suggest that spirocyclopiperazinium derivatives could provide insight on new analgesics.

Background: Fractional flow reserve (FFR) has become an increasingly important index when making decisions with respect to revascularization of coronary artery stenosis. However, the pressure guidewire used in obtaining FFR measurements is difficult to control and manipulate in certain complex coronary artery lesions, resulting in increased fluoroscopy time and contrast dye usage. This study examined a novel (NOV) technique for obtaining FFR measurements in hope of easing the difficulties associated with evaluating and treating complex coronary artery lesions. Methods: Fifty-six patients with complex coronary artery lesions were assigned to a conventional (CON) FFR technique group or a NOV FFR technique group. The NOV technique involved the use of a balloon and wire exchange within the coronary artery. The fluoroscopy time, contrast dye usage, and FFR-related complications were assessed after completing the FFR measurement procedure for each patient. Results: The median time required for fluoroscopy in the NOV technique group was significantly less than that in the CON technique group; additionally, lesser amounts of contrast dye were used in the NOV technique group (both P < 0.05). The NOV technique was successfully performed in thirty patients, without any FFR-related complications. However, the CON technique failed in three patients, including two who experienced coronary artery spasms (P > 0.05). Conclusions: Compared to the CON technique used for measuring FFR, the new technique reduced the fluoroscopy time and amount of contrast dye used when evaluating complex coronary artery lesions. The new technique did not increase the risk of operation or decrease the success rate.

The nanocrystalline SiC films were prepared on Si (111) substrates by rf magnetron sputtering and then annealed at 800°C and 1000°C for 30 minutes in a vacuum annealing system. The crystal structure and crystallization of as-annealed SiC films were determined by the Fourier transform infrared (FTIR) absorption spectra and the X-ray diffraction (XRD) analysis. Measurement of photoluminescence (PL) of the nanocrystalline SiC (nc-SiC) films shows that the blue light with 473 nm and 477 nm wavelengths emitted at room temperature and that the PL peak shifts to shorter wavelength side and the PL intensity becomes stronger as the annealing temperature decreases. The time-resolved spectrum of the PL at 477 nm exhibits a bi-exponential decay process with lifetimes of 600 ps and 5 ns and a characteristic of the direct band gap. The strong blue light emission with short PL lifetimes suggests that the quantum confinement effect of the SiC nanocrystals resulted in the radiative recombination of the direct optical transitions.

Tubulocystic carcinoma of the kidney is a rare entity, which are with about 100 cases of these tumors of the kidney all over the world. We have reported a case, of a 43-year-old man who presented with a lump in the right kidney on image examination without other complaints. Final pathologic diagnosis was tubulocystic carcinoma of the kidney with multiple focal clear cells. Six months after the procedure, the patient remained free of disease. This case showed an indolent manner a low-grade malignancy with favorable prognosis in a short-time follow-up.

NF-kappa B plays a critical role in coordinating the control of gene expression during monocyte/macrophage activation. In this report we describe our investigation of the mechanisms of LPS-induced NF-kappa B activation and IL-12 expression in murine peritoneal suppressor macrophages. Treatment of these macrophages with LPS induced I kappa B alpha degradation and NF-kappa B activation. EMSAs demonstrated that NF-kappa B bound to a cis-acting element located in the murine IL-12 p40 promoter. LPS signal transduction has been shown to involve a variety of signal pathways. The results in this paper indicate that LPS-induced NF-kappa B binding activity was independent of PKC, PHA, ERK, and p38 MAPK, but was regulated by proteasome. Furthermore, Proteasome Inhibitor I abolished the LPS-induced mRNA expression of IL-12 p35 and p40, and SB203580 reduced these mRNA levels, whereas the blockade of PKC, PKA, and ERK had little effect. These data demonstrate that the LPS-induced activation of proteasome I kappa B NF-kappa B and p38 MAPK signal pathways regulate the IL-12 expression in murine peritoneal suppressor macrophages. (C) 2000 Academic Press.

BACKGROUND. Prostate carcinoma progression from an androgen dependent (AD) state to an androgen independent (Al) state occurs clinically in patients who undergo hormonal therapy. In their laboratory, the authors developed two human prostate carcinoma skeletal metastasis models, the LNCaP progression model and the ARCaP model, to investigate phenotypic and genotypic changes of prostate carcinoma cells during disease progression and to understand molecular pathways for potential therapeutic targeting. METHODS. LNCaP or ARCaP cells were inoculated in athymic mice and were exposed to selective hormonal conditions both in vivo and in vitro. The effects of various hormonal treatment regimens on tumor volumes and distant metastasis and the effects of bone stromal cells on prostate specific antigen (PSA) expression by prostate carcinoma cells were evaluated. RESULTS. The authors propose that prostate carcinoma progression from the AD state to the Al state assumes three AI phenotypes: AI that remains androgen responsive, AI that is unresponsive to androgen stimulation, and AI that is suppressed by or hypersensitive to androgen. AI prostate carcinoma cells interacted reciprocally with osteoblasts to produce enhanced tumor growth and osteoblastic reaction when they are deposited in bone. Bone stromal cell conditioned media stimulated prostate carcinoma cell growth and suppressed its PSA expression, as also evidenced by androgen receptor-mediated transactivation of PSA promoter reporter activity. Conditioned media obtained from prostate carcinoma cells also stimulated osteoblastic cell growth in vitro. A novel gene therapy strategy is being developed to target prostatic tumor epithelium and its supporting stroma using tissue specific and tumor-restricted, promoter-directed toxic gene expression in both cellular compartments. In addition, new strategies are being designed to target the tumor endothelial system in the stroma and tumor cell-extracellular matrix interaction mediated by isotype specific integrins. CONCLUSIONS. Prostate carcinoma skeletal metastasis models may prove useful in developing a new targeting strategy for the prevention and treatment of patients with prostate carcinoma.

BACKGROUND Three regions of chromosome 13 were previously identified for having loss of heterozygosity (LOH) in human prostate cancer. One of them, at 13q33, was defined by LOH at markers D13S158 and D13S280. The XPG/ERCC5 gene, a DNA repair gene that when mutated in the germline leads to xeroderma pigmentosum, has been mapped to 13q33, within one megabase of D13S158 and D13S280. This paper describes LOH and mutational analysis of the XPG gene in human prostate cancers, in order to determine whether the XPG gene is involved in the development of prostate cancer. METHODS LOH of the XPG gene was analyzed in 40 primary prostate cancers and 14 metastases by using the microsatellite assay, and its mutations were examined in 5 cell lines, 14 metastases, and 8 tumors with LOH at 13q33 by using the single-strand conformation polymorphism (SSCP)-direct DNA sequencing analysis. RESULTS Four of the 29 (14%) informative primary tumors and 4 of 8 (50%) metastases showed LOH for the XPG gene. Analysis of the 8 tumors with LOH at the 13q33 region, 14 metastases, and 5 cell lines of prostate cancer revealed two polymorphisms but no mutation of the gene. The polymorphism in exon 2 did not change the amino-acid sequence of the XPG protein, but the exon 15 polymorphism altered codon 1104 from histidine to aspartic acid. The two polymorphisms also occurred in individuals without prostate cancer. CONCLUSIONS LOH at XPG in prostate cancer supports the conclusion that the 13q33 region contains a gene important in the development of prostate cancer, while lack of mutations of the gene suggests that XPG is not the target gene involved. Prostate 41:190–195, 1999. © 1999 Wiley-Liss, Inc.

Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.

To explore the effects of glial cell-derived neurotrophic factor (GDNF) on the stem cell factor (SCF), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the undescended testis tissue of rats.Models of left cryptorchidism were made in 48 healthy male rats weighing (200 +/- 20) g and randomly divided into four groups: model control, GDNF 7 d, GDNF 14 d and GDNF 21 d. The rats in the latter three groups were killed at 7, 14 and 21 days after intravenous injection of GDNF, their left testes harvested for measurement of the activities of SOD and CAT and the content of MDA. The apoptosis index of spermatogenic cells was detected by TUNEL, the histological changes of the testis tissue observed under the light microscope, and the gene and protein expressions of SCF determined by real-time quantitative PCR and Western blotting, respectively.The apoptosis indexes of spermatogenic cells were obviously decreased in the GDNF 7 d, GDNF 14 d and GDNF 21 d groups (8.42 +/- 0.16, 4.45 +/- 0.34 and 7.32 +/- 0.09) as compared with that of the model control (13.5 +/- 0.64), with statistically significant difference between the GDNF 14 d and control groups (P0.01). The SCF expression and SOD activity were remarkably increased while the MDA content markedly reduced in the GDNF groups in comparison with those in the model control (P0.01).GDNF had a protective effect on the spermatogenic function of rat testes with unilateral cryptorchidism. It could enhance the antioxidant enzyme activity of the antioxidant enzyme system, elevate the expression of SCF and thus improve the testicular reproductivity, which were best indicated in the GDNF 14 d group.

The aim of this study is to evaluate the diagnostic values of the fluorescence in situ hybridization (FISH), NMP22 BladderChek, and liquid-based cytology (LBC) in the detection of bladder urothelial carcinoma (UC). Consecutive voided urine samples were collected from 138 in-house patients with a variety of urologic conditions and 37 healthy individuals as negative controls. FISH, NMP22 BladderChek, and LBC were performed on the specimens. All three tests were evaluated independently in a blinded fashion. In all, 104 out of the 175 patients enrolled in this study had histologically proven UC. LBC, FISH, and NMP22 BladderChek were successfully performed on 175, 149, and 119 cases, respectively. The three tests revealed overall sensitivities of 73.1%, 86.5%, and 67.6%, respectively. FISH was more sensitive than LBC (P=0.022) and NMP22 BladderChek (P=0.004). Combination of all the tests yielded a superior sensitivity of 96.7% compared with LBC (P

Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of epibatidine incorporated with amino acid ester were synthesized and evaluated for their in vivo analgesic activity and toxicity. Among all tested compounds, compound 6c has the most potent analgesic activity. The quaternary ammonium salts 6a and 6c showed better analgesic activity than the corresponding hydrochlorides 5a and 5c. Both 5a-c and 6a-c showed significantly lower toxicity than epibatidine itself.

To investigate the value of cytokeratin 20 (CK20) immunocytochemical (ICC) detection in the urine liquid-based cytological specimens in diagnosis of urothelial carcinoma (UC).The study consisted of prospective and retrospective groups. In the prospective group, voided urine samples were collected from patients with a variety of urological conditions and healthy individuals. Urine cytological diagnosis and CK20 ICC were performed on the collected specimens. In the retrospective group, archived urine slides with cytological diagnoses of atypical urothelial cells (AUC), suspicious carcinoma (SuCA) and carcinoma (CA) were selected. Then they were re-stained immunocytochemically with monoclonal antibody against CK20 after decolorization. Histological diagnosis and clinical follow-up result were used as the gold standard for analysis.There were 136 cases in the prospective group, including 89 cases of UC, 19 cases of other urogenital malignancies, 12 cases of benign lesions and 16 cases of normal control. The sensitivity of CK20 ICC in detection of UC was 75.3%, significantly higher than that of LBC (48.3%, P0.001). The positive rate of CK20 was 64.7% (22/34) in G1 UC, 73.3% (22/30) in G2 UC, and 91.3% (21/23) in G3 UC (P0.001). The specificity of CK20 ICC was 91.5%, the same as that of LBC. There were 163 cases in retrospective group, including 119 cases of UC, 17 cases of other urogenital malignancies and 27 cases of benign lesions. The cytological diagnoses of them were 68 cases of CA, 47 cases of SuCA and 48 cases of AUC. The positive rates of CK20 ICC in UC and non-UC (other urogenital malignancies and benign lesions) cases were 90.8% and 15.9%, respectively, with a statistically very significant difference (P0.001). The LBC of all the 119 cases of UC included 62 (52.1%) cases of CA, 35 (29.4%) cases of SuCA and 22 (18.5%) cases of AUC. The positive rates of CK20 in the LBC-diagnosed CA, SuCA and AUC were 96.8%, 97.1% and 63.6%, respectively. The LBC of all the 44 non-UC cases included 6 (13.6%) cases of CA, 12 (27.3%) cases of SuCA and 26 (59.1%) cases of AUC, and the positive rates of CK20 in the LBC-diagnosed CA, SuCA and AUC were 33.3%, 33.3% and 3.8%, respectively. The differences of UC and non-UC cases between the corresponding categories of LBC were significant (P0.0001, respectively).CK20 immunocytochemistry as an auxiliary method to urine liquid-based cytology can increase the sensitivity in detection of urothelial carcinomas.

The protein complex of tuberous sclerosis complex (TSC)1 and TSC2 tumor suppressors is a key negative regulator of mammalian target of rapamycin (mTOR). Hyperactive mTOR signaling due to the loss-of-function of mutations in either TSC1 or TSC2 gene causes TSC, an autosomal dominant disorder featured with benign tumors in multiple organs. As the ubiquitous second messenger calcium (Ca(2+)) regulates various cellular processes involved in tumorigenesis, we explored the potential role of mTOR in modulation of cellular Ca(2+) homeostasis, and in turn the effect of Ca(2+) signaling in TSC-related tumor development. We found that loss of Tsc2 potentiated store-operated Ca(2+) entry (SOCE) in an mTOR complex 1 (mTORC1)-dependent way. The endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1), was upregulated in Tsc2-deficient cells, and was suppressed by mTORC1 inhibitor rapamycin. In addition, SOCE repressed AKT1 phosphorylation. Blocking SOCE either by depleting STIM1 or ectopically expressing dominant-negative Orai1 accelerated TSC-related tumor development, likely because of restored AKT1 activity and enhanced tumor angiogenesis. Our data, therefore, suggest that mTORC1 enhancement of store-operated Ca(2+) signaling hinders TSC-related tumor growth through suppression of AKT1 signaling. The augmented SOCE by hyperactive mTORC1-STIM1 cascade may contribute to the benign nature of TSC-related tumors. Application of SOCE agonists could thus be a contraindication for TSC patients. In contrast, SOCE agonists should attenuate mTOR inhibitors-mediated AKT reactivation and consequently potentiate their efficacy in the treatment of the patients with TSC.

Objective To assess the anti-nociception and anti-inflammation pharmacodynamics of Asarum heterotropoides var. mandshuricum and A. sieboldii. Method Both the writhing test and hot plate test were conducted to assess the anti-nociceptive effect of Asarum and Xylene-induced mouse ear edema was conducted to assess the anti-inflammatory effect of Asarum. Result Twelve samples of A. heterotropoides var. mandshuricum and A. sieboldii from different producing areas showed anti-nociceptive and anti-inflammatory effects. Specifically, 27% to 61% of the seven samples of A. heterotropoides var. mandshuricum showed anti-nociceptive effect and while 34% to 48% of A. sieboldi showed anti-nociceptive effect. The inflammatory inhibition rate of A. heterotropoides var. mandshuricum produced in six producing areas (38%-57%) is higher than that of A. heterotropoides var. mandshuricum produced in five producing areas (34%-48%). The same kind of Asarum produced in different areas showed significant differences. A. heterotropoides var. mandshuricum produced in Jilin province (38%-57%) showed better anti-nociceptive effect than sample produced in Heilongjiang province (34%) in writhing test. A. heterotropoides var. mandshuricum produced in Heilongjiang (43%) province showed a better anti-nociceptive effect than samples produced in Liaoning province (29%-36%) in hot plate test. A. sieboldii produced in Shaanxi province (47%-49%) showed a better anti-nociceptive effect than samples produced in Hubei province (40%) in writhing test. A. sieboldii produced in Shaanxi province (45%-59%) showed better anti-nociceptive effect than samples produced in Chongqing (40%) in hot plate test. A. heterotropoides var. mandshuricum produced in Jilin province (51%-63%) showed better anti-inflammatory effect than samples produced in Heilongjiang province (50%). In totality, the results from analysis of geoherbalism showed that famous-region A. heterotropoides var. mandshuricum and A. sieboldii had a better anti-nociception effect than Asarum produced in other producing areas, famous-region A. heterotropoides var. mandshuricum had a better effect than those produced in other producing areas in anti-inflammation. But famous-region A. sieboldii showed no obvious difference from those produced in other producing areas in anti-inflammation. Conclusion All samples of Asarum showed anti-nociceptive and anti-inflammatory effects, but with significant differences among Asarum produced in different areas, indicating the eoherbalism to some extent.

The aim of this study is to evaluate the diagnostic values of the fluorescence in situ hybridization (FISH), NMP22 BladderChek, and liquid-based cytology (LBC) in the detection of bladder urothelial carcinoma (UC). Consecutive voided urine samples were collected from 138 in-house patients with a variety of urologic conditions and 37 healthy individuals as negative controls. FISH, NMP22 BladderChek, and LBC were performed on the specimens. All three tests were evaluated independently in a blinded fashion. In all, 104 out of the 175 patients enrolled in this study had histologically proven UC. LBC, FISH, and NMP22 BladderChek were successfully performed on 175, 149, and 119 cases, respectively. The three tests revealed overall sensitivities of 73.1%, 86.5%, and 67.6%, respectively. FISH was more sensitive than LBC (P=0.022) and NMP22 BladderChek (P=0.004). Combination of all the tests yielded a superior sensitivity of 96.7% compared with LBC (P0.001), NMP22 BladderChek (P0.001), and FISH (P=0.016), with the specificity only decreased slightly. Sensitivities of the three tests enhanced significantly with increasing UC grade (P0.05). The positive rates of FISH and NMP22 BladderChek in equivocal cytologic diagnoses were 85.7% and 61.9% in UC, and 37.5% and 50.0% in non-UC (FISH: P=0.021; NMP22 BladderChek: P=0.683). FISH was more sensitive than LBC and NMP22 BladderChek. FISH had the ability to clarify equivocal cytologic diagnoses. Combination of all three tests showed an improvement in the sensitivity compared to any single test alone in detecting UC with the specificity slightly decreased.

Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH has been under-investigated in China. The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China.In this prospective, open-label and multi-center study, 90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks. They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks. The primary endpoint was the changes in exercise capacity as assessed by SMWT. And the secondary endpoints included assessment of functional class, evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death, transplantation and re-hospitalization for PAH). Drug safety and tolerability were also examined.There were 19 males and 71 females with an average age of 32.5 ± 12.1 years old (range: 18 - 61). Their etiologies were idiopathic (n = 15), related with congenital heart disease (n = 60), or related with connective tissue disease (n = 9) and chronic thromboembolic pulmonary hypertension (n = 6). Oral sildenafil significantly increased the SMWT distances [(342 ± 93) m vs. (403 ± 88) m, P0.001]. There was also remarkable improvement in Borg dyspnea score (2.9 ± 2.6 vs. 2.4 ± 2.0, P = 0.005). Furthermore, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found (mean pulmonary artery pressure, P0.001; cardiac index, P0.001; pulmonary vascular resistance, P0.001). Side effects were mild and consistent with other reports.This study confirms and extends previous studies. Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

The impact of sildenafil on pulmonary arterial hypertension (PAH) in Chinese patients has been less investigated. A prospective, open-label, uncontrolled and multicenter study, therefore, was carried out to address this issue. Ninety patients with multicause-induced PAH received oral sildenafil (75 mg/day) for 12 weeks. The 6-minute walk test (SMWT) and cardiac catheterization were performed at the beginning and the end of the 12 weeks. The primary endpoint was the changes in exercise capacity assessed by the SMWT; the secondary endpoint included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening. Drug safety and tolerability were also examined. The results showed that there was a significant improvement in SMWT distances (342 ± 93 m vs 403 ± 88 m, P < .0001), Borg dyspnea score (2.9 ± 2.6 vs 2.4 ± 2.0, P = .0046), World Health Organization functional class, and cardiopulmonary hemodynamics (mean pulmonary artery pressure, P < .0001; cardiac index, P < .0001; pulmonary vascular resistance, P < .0001) after 12 weeks of oral sidenafil therapy. Almost all enrolled patients did not experience significant clinical worsening. This study confirms and extends the findings of previous studies relating to effects of sildenafil on PAH, suggesting that oral sildenafil is safe and effective for the treatment of adult patients with PAH in the Chinese population.

To analyze the clinical efficacy of combined therapy in the treatment of advanced adrenal cortical adenocarcinoma.The clinical data of 12 cases with advanced adrenal cortical adenocarcinoma at our hospital from 1986 - 2006 were analyzed. And the relevant literatures were reviewed.Eleven patients underwent operation to remove primary lesions. Only 1 case received a biopsy. All cases were treated with chemotherapy or chemotherapy pulse post-operative radiotherapy. Pathological diagnosis was all of adrenal cortical adenocarcinoma. According to the staging criteria of Jacques and Brennan, all 12 cases were of IV stage. The follow-up duration was 6 - 40 months. According to evaluation criterion of chemotherapeutic effect by WHO in 1987, the results were: CR (complete remission) (n = 0), PR (partial remission) (n = 7), SD (stable disease) (n = 3) and PD (progressive disease) (n = 2). The effective rate was 58.3% (7/12). The median survival time was 14 months and median progression-free survival time 9 months.Combined therapy of adrenal cortical adenocarcinoma is effective to prolong the patient lifespan. Radiotherapy offers partial symptomatic relief for those with osseous metastasis. Making an early diagnosis and offering a novel therapy yield a better outcome.