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Human serum albumin (HSA) is a non-glycosylated, negatively charged, single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD. It is synthesized by the liver at a rate of approximately 200 mg·kg−1·day−1, with a half-life of 21 days, and subjected to catabolism in the muscles, liver, and kidneys at a rate of 4% per day.[1] Albumin, accounting for 60% of the total plasma protein, has various physiological functions,[2] such as maintaining 70% to 80% of effective plasma colloid osmotic pressure, coordinating vascular endothelial integrity, anti-oxidant and anti-inflammatory activities, maintaining the acid-base balance, and participating in the transport, distribution, and metabolism of a variety of endogenous and exogenous substances. The normal concentration of plasma albumin is 35 to 50 g/L. In clinical practice, hypoalbuminemia often occurs because of reduced albumin synthesis due to liver dysfunction, redistribution of serum albumin due to capillary leakage, or increased loss via the intestinal and renal routes. Hypoalbuminemia (defined as a serum albumin concentration less than 35 g/L) reportedly has an incidence of 24% to 87% in critically ill patients,[3] while severe hypoalbuminemia (a serum albumin concentration less than 25 g/L) has an incidence of 5.0–9.6%.[4] Hypoalbuminemia is an independent risk factor for increased short- and long-term mortality and an increased incidence of acute kidney injury (AKI) in patients with acute conditions such as trauma, cardiogenic shock, and sepsis.[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay.[6] Hypoalbuminemia can also alter the pharmacokinetics of antibiotics, leading to either insufficient or excessively high blood concentrations, thereby resulting in treatment failure or excessive toxicity.[7] HSA is mainly used for fluid resuscitation and the treatment of hypoproteinemia in critically ill patients.[2] Existing studies have shown controversial results regarding whether the use of albumin in critically ill patients improves their clinical prognosis.[8] Albumin consumption varies greatly among countries,[9] and its inappropriate use is frequently seen, with 40% to 90% of reported HSA applications failing to follow clinical guidelines.[10] A tertiary hospital in China reported that hypoproteinemia was the most common indication for the use of HSA (35.6%); however, it was also used in 11.8% of patients with serum albumin concentrations more than 40 g/L. The reason for its use was not documented in 22% of cases.[11] In clinical practice, guidelines and consensus are lacking regarding the selection of HSA concentration, the timing of administration, dosage, and target concentration. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis.[12] To further strengthen the standardized application of HSA in critically ill patients and achieve optimal clinical outcomes, the Chinese Society of Critical Care Medicine convened a panel of relevant experts who reviewed and summarized data on the clinical use of HSA, outlined 11 relevant clinical problems, and formulated the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Background: There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine. Methods: From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database. Results: The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species. Conclusions: Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations. Key words: Hypertrophic cardiomyopathy; MYH7; Gene mutation; Pathology

Background: Coronary calcification is a major determinant of stent underexpansion and subsequent adverse events. This study aimed to evaluate the acute- and long-term outcomes of rotational atherectomy (RA) followed by cutting balloon (CB) versus plain balloon before drug-eluting stent implantation for calcified coronary lesions. Methods: From June April 2013 to March 2016, a total of 127 patients with moderately or severely calcified coronary lesions were treated with RA. Patients were divided into two groups according to the balloon type after RA: RA+CB group (n = 75) and RA+plain balloon group (n = 52). Minimal lumen diameter and acute lumen gain were analyzed by quantitative coronary angiography. In-hospital and long-term (>1 year) outcomes were recorded. Multivariate Cox regression analysis was performed to determine the independent predictors of in-stent restenosis. Results: The mean age of the patients was 65.5 years, and 76.4% were men. Total lesion length and minimal lumen diameter at baseline were similar in the two groups. After RA and balloon dilation, the lumen diameter was significantly larger in the RA+CB group than in the RA+plain balloon group (1.57 ± 0.46 mm vs. 1.10 ± 0.40 mm, t = 4.123, P < 0.001). The final lumen diameter was also larger in the RA+CB group compared to that in the RA group (2.81 ± 0.41 mm vs. 2.60 ± 0.25 mm, t = 2.111, P = 0.039). Moreover, patients receiving RA and CB tended to have larger final lumen gain (2.15 ± 0.48 mm vs. 1.95 ± 0.47 mm, t = 1.542, P = 0.132). Multivariate Cox regression analysis indicated that the strategy of RA+CB was a significant protective factor against long-term (>1 year) in-stent restenosis (hazard ratio: 0.136, 95% confidence interval: 0.020–0.936, P = 0.043). Conclusions: In patients with moderately or severely calcified lesions, a strategy of RA followed by CB before stent implantation can increase lumen diameter and acute lumen gain. This strategy is safe with lower risk of long-term in-stent restenosis.

Background: Renal cell carcinoma (RCC) is frequently associated with paraneoplastic inflammatory syndrome (PIS). This study aimed at exploring the connections between the survival rate and specific gene alterations and the potential mechanism. Methods: We retrospectively studied 69 surgical RCC cases from August 2014 to February 2016, including 18 cases of clear cell RCC (ccRCC) demonstrating elevated pretreatment serum C-reactive protein (CRP, Group A). Twelve of the 18 cases were symptomized with febrile episode. We also selected 49 cases of ccRCC with normal pretreatment CRP (Group B). Using 22 microsatellite markers, we compared the incidence of loss of heterozygosity (LOH) between Group A and Group B. All statistical tests are two-sided. Results: The 3p LOH was common in both Group A (89%) and Group B (92%). The frequency of 14q LOH in Group A (16 of 18) was higher than Group B (4 of 49, χ2 = 40.97 P < 0.0001). The 3p and 14q LOH were the characteristics of ccRCC with elevated acute phase reactants, including PIS, regardless of the presence of metastasis. On the contrary, 14q LOH was a rare genomic alternation in advanced-staged ccRCC without PIS. The overall survival of patients with elevated CRP (33.3%) was lower than its counterparts (6.1%, hazard ratio=1.852, P < 0.0001) in Kaplan-Meier curve. Conclusions: The results imply that the disruption of a 14q gene(s) might result in not only the inflammatory manifestations in the tumor host but also the poor survival rate as well. The isolation of the gene(s) on 14q might be a vital goal in the treatment of PIS-associated RCC. Key words: C-reactive Protein; Gene Alterations; Loss of Chromosome; Paraneoplastic Inflammatory Syndrome; Renal Cell Carcinoma

Background: Surgical ventricular restoration (SVR) has been performed to treat left ventricular (LV) aneurysm. However, there is limited analysis of changes in LV shape. This study aimed to evaluate the changes in LV shape induced by SVR and the effects of SVR on LV size and function for LV aneurysm. Methods: Between April 2006 and March 2015, 18 patients with dyskinetic (dyskinetic group) and 12 patients with akinetic (akinetic group) postinfarction LV anterior aneurysm receiving SVR with the Dor procedure at Chinese People's Liberation Army General Hospital were enrolled in this study. A retrospective analysis was carried out using data from the echocardiography database. LV shape was analyzed by calculating the apical conicity index (ACI). LV end-diastolic volume index, end-systolic volume index, and ejection fraction (EF) were measured. One-way analysis of variance was used to compare means at different time points within each group. Results: Within one week after SVR, LV shape became more conical in the two groups (ACI decreased from 0.84 ± 0.13 to 0.69 ± 0.11 [ t = 5.155, P = 0.000] in dyskinetic group and from 0.73 ± 0.07 to 0.60 ± 0.11 [ t = 2.701, P = 0.026] in akinetic group; LV volumes were decreased significantly and became closer to normal values and EF was improved significantly in the two groups). On follow-up at least one year, LV shape remained unchanged in dyskinetic group (ACI increased from 0.69 ± 0.11 to 0.74 ± 0.12, t = −1.109, P = 0.294), but became more spherical in akinetic group (ACI significantly increased from 0.60 ± 0.11 to 0.75 ± 0.11, t = −1.880, P = 0.047); LV volumes remained unchanged in dyskinetic group, but increased significantly in akinetic group and EF remained unchanged in the two groups. Conclusions: SVR could reshape LV to a more conical shape and a more normal size and improve LV function significantly early after the procedure in patients with dyskinetic or akinetic postinfarction LV anterior aneurysm. However, LV tends to be more spherical and enlarged in the akinetic group on at least 1-year follow-up.

Background: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. Methods: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. Results: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. Conclusions: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided. Key words: Laparoscopic Myomectomy; Morcellation; Sarcoma

Background: Enhanced recovery after surgery (ERAS) protocols or fast-track (FT) programs enable a shorter hospital stay and lower complication rate. Minimally invasive surgery (MIS) is associated with a lesser trauma and a quicker recovery in many elective abdominal surgeries. However, little is known of the safety and effectiveness made by ERAS protocols combined with MIS for gastric cancer. The purpose of this study was to evaluate the safety and effectiveness made by FT programs and MIS in combination or alone. Methods: We summarized an 11-year experience on gastric cancer patients undergoing elective laparotomy or minimally invasive gastric resection in standard cares (SC) or FT programs during January 2004 to December 2014. A total of 984 patients were enrolled and assigned into four groups: open gastrectomies (OG) with SC (OG + SC group, n = 167); OG with FT programs (OG + FT group, n = 277); laparoscopic gastrectomies (LG) with FT programs (LG + FT group, n = 248); and robot-assisted gastrectomies (RG) with FT programs (RG + FT group, n = 292). Patients’ data were collected to evaluate the clinical outcome. The primary end point was the length of postoperative hospital stay. Results: The OG + SC group showed the longest postoperative hospital stay (mean: 12.3 days, median: 11 days, interquartile range [IQR]: 6–16 days), while OG + FT, LG + FT, and RG + FT groups recovered faster (mean: 7.4, 6.4, and 6.6 days, median: 6, 6, and 6 days, IQR: 3–9, 4–8, and 3–9 days, respectively, all P < 0.001). The postoperative rehabilitation parameters such as flatus time after surgery (4.7 ± 0.9, 3.1 ± 0.8, 3.0 ± 0.9, and 3.1 ± 0.9 days) followed the same manner. After 30 postoperative days’ follow-up, the total incidence of complications was 9.6% in OG + SC group, 10.1% in OG + FT group, 8.1% in LG + FT group, and 10.3% in RG + FT group. The complications showed no significant differences between the four groups (all P > 0.05). Conclusions: ERAS protocols alone could significantly bring fast recovery after surgery regardless of the surgical technique. MIS further reduces postoperative hospital stay. It is safe and effective to apply ERAS protocols combined with MIS for gastric cancer.

To the Editor: The methods for obstruction of colon cancer include emergency surgery or self-expanding metallic stents (SEMSs). SEMS insertion was shown to be a safe, easy, and effective treatment for left-sided malignant colon obstruction, for palliative treatment or as bridge to resection.[12345]

BACKGROUND Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders. METHODS A diabetic guinea pig model was produced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 (10 - 100 microg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10 micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS We established a guinea pig model of delayed gastric emptying. Ghrelin (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100 microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05). Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSIONS Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

Drug-eluting stents represent a major advance in interventional cardiology. However, the current drug-eluting stents have significant limitations. One of the major problems is very late stent thrombosis, which is likely caused by inflammation and a hypersensitivity reaction related to a polymer on the stent. A polymer-free sirolimus-eluting stent with a unique nano-porous surface has been developed. This study aimed to evaluate this novel polymer-free sirolimus-eluting stent for its efficacy and safety in a pig model.Stents were directly coated with sirolimus (a drug concentration of 2.2 µg/mm(2) on the stent surface). The polymer-free sirolimus-eluting stents (PFSES) were compared to standard polymer-coated sirolimus-eluting stents (PCSES) and bare-metal stents (BMS) in 18 pigs.At one month the degree of neointimal hyperplasia was similar between the two sirolimus-eluting stent groups and was significantly less compared to BMS ((1.93 ± 0.51) mm(2), (1.57 ± 0.69) mm(2) vs. (4.45 ± 1.05) mm(2), P0.05) At three months, PFSES maintained the low level of neointima ((2.41 ± 0.99) mm(2) vs. (4.32 ± 1.16) mm(2), P0.05), whereas PCSES had developed significant neointimal proliferation similar to BMS. The inflammation level was significantly higher in PCSES when compared with BMS three months post-implantation (2.50 ± 0.55 vs. 0.83 ± 0.75, P0.05) whereas PFSES showed a low level of inflammation comparable to PCSES (1.33 ± 0.52 vs. 2.50 ± 0.55, P0.05).The PFSES is effective and safe, and appears to be superior to standard PCSEs.

Left atrial (LA) maximum volume is becoming a prognostic biomarker for left ventricular (LV) diastolic dysfunction. However, we assessed LV diastolic function by measuring LA phasic volumes using real-time threedimensional echocardiography (RT3DE) in patients with stable coronary artery disease (CAD).Sixty-five stable CAD patients with normal LV ejection fraction (LVEF) were divided into three groups according to degree of coronary stenosis: control (n = 15) with50% stenosis as control group, mildS (n = 25) with mild stenosis (50%-70%) and severeS (n = 25) with70% stenosis. LA phasic volumes and function were evaluated and compared using RT3DE and two dimensional echocardiography (2DE). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were examined. The correlations of RT3DE-derived parameters with other conventional indices were analyzed.Significant correlations between RT3DE and 2DE for LA volume measurements were: control, r = 0.93; mildS, r = 0.94; severeS, r = 0.90 (all P0.05). Patients with severe coronary stenosis presented higher NT-proBNP level, indices of LA minimum volume and volume before atrial contraction, but lower LA total emptying fraction (LAEF) and LAEFpassive. Significant correlations of RT3DE derived LA volume indices with E/E' (r = 0.695) and NF-proBNP (r = 0.630) level were found.RT3DE derived, LA indices correlate well with NT-proBNP level and may be superior to 2DE measurements for the evaluation of LV diastolic dysfunction. Enlargement of LA minimum volume in stable CAD patients without systolic dysfunction appears earlier and may be better correlated with LV diastolic function than that of LA maximum volume.

A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Pressure therapy improves hypertrophic scar healing, but the mechanisms for this process are not well understood. We sought to investigate the differential expression of matrix metalloproteinases (Mmps) and collagen in posttraumatic hypertrophic scar tissue with mechanical pressure and delineate the molecular mechanisms of pressure therapy for hypertrophic scars.Fibroblast lines of normal skin and scar tissue were established and a mechanical pressure system was devised to simulate pressure therapy. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting assays were used to compare differences in the mRNA and protein expression of Mmps and collagen in scar fibroblasts before and after pressure therapy.The expression differed between the hypertrophic scar cell line and the normal cell line. RT-PCR assays showed that Collagen I, highly expressed in the hypertrophic scar cell line, decreased significantly after pressure therapy. Mmp2, Mmp9, and Mmp12 expression in the hypertrophic scar tissue increased significantly after pressure therapy (P0.05). Western blotting assays further revealed that Mmp9 and Mmp12 expression increased significantly in the hypertrophic scar tissue after pressure therapy (P0.05) but not Mmp2 expression (P0.05).Mechanical pressure induces degradation of Collagen I in hypertrophic scar tissue by affecting the expression of Mmp9 and Mmp12.

Robotic assisted minimally invasive cardiac sugery is a new technique that uses small port sites and peripheral vessel cannulation for cardiopulmonary bypass (CPB) has been used. The right internal jugular vein (IJV) is commonly used for intraoperative venous access to the central circulation and identified with an external landmark. Previous studies have demonstrated the superiority of ultrasound guidance over external landmark technique in anaesthetic and intensive care settings. The aim of the present study was to delineate the utility of ultrasound-guided cannulation of the IJV during establishment of peripheral CPB in robotic cardiac surgery.We prospectively studied 296 adult patients undergoing ultrasound-guided right IJV cannulation during establishment of peripheral CPB in robotic cardiac surgery at our institute from January 2007 to October 2012 (ultrasound group). The success rate, the first attempt success rate, access time and the complication rate of ultrasound-guided method were compared with the landmark-guided method used for 302 historical control patients (landmark group).In the ultrasound group, 296 consecutive adult patients underwent ultrasound-guided right IJV cannulation during establishment of peripheral CPB in robotic cardiac surgery. In the landmark group, 302 patients underwent right IJV cannulation using the landmark-guided technique. The success rate and the frst attempt success rate in the ultrasound group were significantly higher than that in the landmark group (100% vs. 88.1%, P0.000 and 98.6% vs. 38.4%, P0.000). Average access time in the ultrasound group was shorter than that in the landmark group ((6.3 ± 13.6) seconds; interquartile range (4 - 62) seconds vs. (44.5 ± 129.5) seconds; interquartile range (5 - 986) seconds). The complication rate in the ultrasound group was significantly lower than that in the landmark group (0.3% vs. 8.3%, P0.000).Compared with the landmark-guided approach, ultrasound-guided cannulation of the right IJV significantly improves success rate, decreases access time and reduces complication rate during establishment of peripheral CPB in robotic cardiac surgery.

Asthma is a heterogeneous disease for which a strong genetic basis has been firmly established. Until now no studies have been undertaken to systemically explore the network of asthma-related genes using an internally developed literature-based discovery approach. This study was to explore asthma-related genes by using literature-based mining and network centrality analysis.Literature involving asthma-related genes were searched in PubMed from 2001 to 2011. Integration of natural language processing with network centrality analysis was used to identify asthma susceptibility genes and their interaction network. Asthma susceptibility genes were classified into three functional groups by gene ontology (GO) analysis and the key genes were confirmed by establishing asthma-related networks and pathways.Three hundred and twenty-six genes related with asthma such as IGHE (IgE), interleukin (IL)-4, 5, 6, 10, 13, 17A, and tumor necrosis factor (TNF)-alpha were identified. GO analysis indicated some biological processes (developmental processes, signal transduction, death, etc.), cellular components (non-structural extracellular, plasma membrane and extracellular matrix), and molecular functions (signal transduction activity) that were involved in asthma. Furthermore, 22 asthma-related pathways such as the Toll-like receptor signaling pathway, hematopoietic cell lineage, JAK-STAT signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interaction, and 17 hub genes, such as JAK3, CCR1-3, CCR5-7, CCR8, were found.Our study provides a remarkably detailed and comprehensive picture of asthma susceptibility genes and their interacting network. Further identification of these genes and molecular pathways may play a prominent role in establishing rational therapeutic approaches for asthma.

Virtual reality (VR) has been recognized as a useful modality in the training of surgical skills. With respect to basic endoscopic skill training of urology, we sought to investigate the effectiveness of the UroMentor(TM) virtual reality simulator (VRS) in the skill acquisition of flexible cystoscopy.Urologists familiar with rigid cystoscopy procedures were selected to take part in a virtual training course of flexible cystoscopy. Changes in total operating time, frequency of injury, number of digital markers inside the bladder, and the global rating scale (GRS) scores were assessed following eight repeated training sessions on the UroMentor(TM).Eighteen urologists voluntarily took part in the study. Total operating time was significantly lower after eight sessions of training by comparison ((111 ± 10) seconds and (511 ± 67) seconds, respectively; P0.001). Additionally, the frequency of injury decreased with training from (12 ± 2) times to (5 ± 1) times (P0.001), while the number of digital markers observed increased from 9 ± 0 to 10 ± 1 (P = 0.005). Finally, training with the UroMentor(TM) resulted in a GRS increase from (1.3 ± 0.2) points to (3.9 ± 0.2) points (P0.001).the VRS UroMentor(TM) can improve urologists' ability to perform flexible cystoscopy and could be used as an effective training tool for trainees.

Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR).Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

The need to develop new methods of surgical training combined with advances in computing has led to the development of virtual reality surgical simulators. The PERC Mentor(TM) is designed to train the user in percutaneous renal collecting system access puncture. This study aimed to validate the use of this kind of simulator, in percutaneous renal access training.Twenty-one urologists were enrolled as trainees to learn a fluoroscopy-guided percutaneous renal accessing technique. An assigned percutaneous renal access procedure was immediately performed on the PERC Mentor(TM) after watching instruction video and an analog operation. Objective parameters were recorded by the simulator and subjective global rating scale (GRS) score were determined. Simulation training followed and consisted of 2 hours daily training sessions for 2 consecutive days. Twenty-four hours after the training session, trainees were evaluated performing the same procedure. The post-training evaluation was compared to the evaluation of the initial attempt.During the initial attempt, none of the trainees could complete the appointed procedure due to the lack of experience in fluoroscopy-guided percutaneous renal access. After the short-term training, all trainees were able to independently complete the procedure. Of the 21 trainees, 10 had primitive experience in ultrasound-guided percutaneous nephrolithotomy. Trainees were thus categorized into the group of primitive experience and inexperience. The total operating time and amount of contrast material used were significantly lower in the group of primitive experience versus the inexperience group (P = 0.03 and 0.02, respectively).The training on the virtual reality simulator, PERC Mentor(TM), can help trainees with no previous experience of fluoroscopy-guided percutaneous renal access to complete the virtual manipulation of the procedure independently. This virtual reality simulator may become an important training and evaluation tool in teaching fluoroscopy-guided percutaneous renal access.

A virtual reality simulator provides a novel training model for improving surgical skills in a variety of fields. They can simulate a variety of surgical scenarios to improve the overall skills required for endoscopic operations, and also record the operative process of trainees in real-time and allow for objective evaluation. At present, some simulators for transurethral resection of the prostate (TURP) are available. The utility of virtual reality simulators in training of transurethral prostatectomy was investigated.Thirty-eight urologists were randomly selected to take part in a simulation based training of TURP using the TURPSim(TM) system. Pre and post-training global rate scale (GRS) scores and objective parameters recorded by the simulator were assessed. Then, questionnaires were filled out.Compared with baseline levels, the GRS scores of trainees increased (18.0 ± 4.0 vs. 12.4 ± 4.2, P0.001), while the rate of capsule resection (26.3% ± 0.6% vs. 21.2% ± 0.4%, P0.001), amount of blood loss ((125.8 ± 86.3) ml vs. (83.7 ± 41.6) ml, P0.001), external sphincter injury (3.6 ± 2.9 vs. 2.0 ± 2.0, P0.001) decreased significantly after training. Most trainees were satisfied with the simulator based training and believed that the simulator accurately mimicked actual surgical procedures and could help improve their surgical skills.As a new method of training on transurethral prostatectomy skills, training of TURP using a virtual simulator can help urologists improve their surgical skills and safety. Therefore, the application of the TURPSim(TM) system in education and training of urologic surgery is warranted.

Mycophenolate mofetil (MMF) has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure. The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 (TLR4) signaling in the early stages of renal ischemia/reperfusion injury (IRI) of mice.Sixty BALB/C mice were randomly divided into two groups: an IRI group, in which renal IRI was induced by clamping the renal pedicles for 45 minutes, and an MMF group, in which MMF was given (40 mg×kg(-1)×d(-1), intraperitoneally) from 2 days before renal IRI. The plasma creatinine level and renal tissue damage of each group mice were observed 6, 12, 24, and 48 hours after reperfusion. The concentration of plasma high-mobility group box 1 (HMGB-1) (TLR4 ligand), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) and the expression of TLR-4 on monocytes were determined.The plasma creatinine concentration in the MMF group was lower compared to the IRI group (after reperfusion of 6, 12, 24, or 48 hours, P0.05). Pathological analysis showed that the renal damage was slighter, TLR-4 expression was reduced (after reperfusion of 6, 12, 24, or 48 hours, P0.05), and the concentration of cytokines in the plasma was lower (P0.05) in the MMF group. No differences in the concentrations of HMGB-1 were observed (P0.05).Monocyte TLR4 signaling is important in the early stage of kidney IRI, but MMF can inhibit it and improve renal function.

The initial classic classification of duplex kidney into complete (two ureters) and incomplete ("Y" shaped ureter) types are based on the ureter status. At the meantime, the features of the upper and lower moieties of duplex kidney were very crucial for appropriate procedure of hemi-nephrectomy, which was most commonly used for addressing the issues caused by a duplex kidney; and recently more applications of laparoscopy were used. In this study, we aimed prudently to propose a new classification based on the features of the upper and lower moieties of duplex kidney.Sixty-five children with 83 duplex kidneys were reviewed retrospectively. Based on kidney morphology found in CT urography and surgical findings, duplex kidney was classified into five types.The first was the appendant type (36/83) and its feature was that the mini upper moiety was located on top of the lower one, with a visualized shallow groove between them. The ureter was dilated with an ectopic orifice or ureterocele. The second was the embedded type (13/83), the feature of which was that mini upper moiety located in the interior top of the lower one within the same capsule. The upper ureter was dilated with an ectopic orifice or ureterocele. The third was the hydronephrosis type (12/83). The severe hydronephrotic upper moiety was almost as big as the lower moiety. The upper ureter was severely dilated and circuitous with an ectopic orifice. The forth was the dual-poor type (2/83). The two moieties were all very small with "Y" shaped ureters and ectopic orifices. The last was the dual-well type (20/83). The upper moiety was almost the same size as the lower one, without apparent dilation of "Y" shaped or double ureters.Based on kidney morphology, duplex kidney can be mainly classified into five types which can be depicted by CT urography prior to management and can provide an aid in selecting a successful course of surgical correction.

Vibrio vulnificus (Vv) is an estuarine bacterium that can cause primary septicemia as well as serious wound infections. However, little is known about the mechanisms by which Vv infects dendritic cells (DCs) and its effects on cytoskeleton. In this study, we aimed to investigate the invasion, internalization, and the organelles damage of the cultured dendritic cells (a DC 2.4 strain) during Vv infection.The study model was the cultured DCs infected by a Vv 1.758 strain. Electron microscopy was used to observe the localization of bacteria at the different time points of infection, cell morphology, and the process of organelles changes. The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined under a fluorescence microscope.The Vv were pinocytosised into the DC cells through double-sides, and localized at 1 - 2 mm of the inner side membrane. It took 1.3, 1.9, and 3.4 hours to reach the infection ratio of 25%, 50%, and 75%, respectively. Using electron microscopy, the DCs had been observed to have developed chromatin aggregation within 4.0 hours, and significant cytoskeleton structure disruption was noted within 6.0 hours.The high lethality of Vv infection may be associated with the direct disruption of the DCs cytoskeleton structure.

Stent-based delivery of sirolimus has been shown to reduce neointimal hyperplasia significantly. However, the long-term effect of the polymer is thought to initiate and sustain an inflammatory response and contribute to the occurrence of late complications. Our study aimed to evaluate the efficacy and safety of the BuMA biodegradable drug-coated sirolimus-eluting stent (BSES) for inhibiting neointimal hyperplasia in a porcine coronary model.Four types of stents were implanted at random in different coronary arteries of the same pig: BSES (n = 24), bare metal stent (BMS) (n = 24), biodegradable polymer coated stent without drug (PCS) (n = 24) and only poly (n-butyl methacrylate) base layer coated stent (EGS) (n = 23). In total, 26 animals underwent successful random placement of 95 oversized stents in the coronary arteries. Coronary angiography was performed after 28 days, 90 days and 240 days of stent implantation. After 14 days, 28 days, 90 days and 240 days, 6 animals at each timepoint were sacrificed for histomorphologic analysis.The 28-day, 90-day and 240-day results of quantitative coronary angiography (QCA) showed reduction in luminal loss (LL) in the BSES group when compared with the BMS group; (0.20 ± 0.35) mm vs. (0.82 ± 0.51) mm (P = 0.035), (0.20 ± 0.30) mm vs. (0.93 ± 0.51) mm (P = 0.013), and (0.18 ± 0.16) mm vs. (0.19 ± 0.24) mm (P = 0.889), respectively. By 28-day, 90-day and 240-day histomorphomeric analysis results, there was also a corresponding significant reduction in neointimal tissue proliferation with similar injury scores of BSES compared with the BMS control; average neointimal area (0.90 ± 0.49) mm(2) vs. (2.16 ± 1.29) mm(2) (P = 0.049), (1.53 ± 0.84) mm(2) vs. (3.41 ± 1.55) mm(2) (P = 0.026), and (2.43 ± 0.95) mm(2) vs. (3.12 ± 1.16) mm(2) (P = 0.228), respectively. High magnification histomorphologic examination revealed similar inflammation scores and endothelialization scores in both the BSES and BMS groups.The BuMA biodegradable drug-coated sirolimus-eluting stents can significantly reduce neointimal hyperplasia and in-stent restenosis. Re-endothelialization of the BuMA stent is as good as that of the BMS in the porcine coronary model due to the reduced inflammation response to the BuMA stent.