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Sepsis-associated acute renal injury (SA-AKI) is a common critical clinical disease. It is associated with increased mortality and increased risk of progression to chronic kidney disease. However, its pathogenesis is not fully known. We hypothesized that metabolic interactions mediate cell apoptosis and AKI. We found that phosphatidylcholine content in human renal tubular epithelial cells following lipopolysaccharide-induced injury was increased. The activity of lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme in phospholipid metabolism, was increased, while the expression of miR-124-3p.1, which targets LPCAT3, was decreased. We also found that in the serum of SA-AKI patients, LPCAT3 activity was increased, and miR-124-3p.1 expression was decreased. Further experiments confirmed the specific binding of exocrine miR-124-3p.1 to LPCAT3. Our data reveal the molecular mechanisms of phospholipid metabolic disorder in early SA-AKI as well as the role of the miR-124-3p.1/LPCAT3 pathway in SA-AKI, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in SA-AKI.

Background: Retroperitoneal approach and segmental renal artery clamping in partial nephrectomy are techniques that facilitate postoperative recovery and renal function preservation. This study aimed to compare the renal function preservation and perioperative outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) with these techniques. Materials and Methods: Clinical parameters of 43 patients who had undergone retroperitoneal RAPN from March 2017 to December 2019 were retrospectively collected and compared with those of 52 patients who had undergone retroperitoneal LPN at the same period in our institution. Differences in operating time, warm ischemia time, estimated blood loss, complications, postoperative hospital stay, as well as renal function loss were compared between the two groups. Results: Background characteristics between RAPN and LPN groups such as age, gender, BMI, and tumor characteristics were comparable. All RAPNs and LPNs were successfully completed without conversion to open surgery or nephrectomy. No significant difference in operating time, estimated blood loss, complications, and postoperative hospital stay was observed between RAPN and LPN groups. The warm ischemia time in RAPN group was slightly shorter than that of LPN groups (P = .054). Compared with the LPN group, the RAPN group was significantly associated with less glomerular filtration rate reduction and renal volume loss rate (P = .042 and P = .013, respectively). Conclusions: The perioperative outcomes were comparable between the two groups. However, compared with LPN, RAPN had superiority in preserving renal function in our series.

Background Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. Methods We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. Results We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51–1.17) in the 90th percentile of SO2 (19.6 μg/m3) and 0.41 (95% CI: 0.27–0.64) in the 10th percentile of SO2 (10.6 μg/m3). Conclusion Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.

BackgroundCopper-induced cell death has been widely investigated in human diseases as a form of programmed cell death (PCD). The newly recognized mechanism underlying copper-induced cell death provided us creative insights into the copper-related toxicity in cells, and this form of PCD was termed cuproptosis.MethodsThrough consensus clustering analysis, ccRCC patients from TCGA database were classified into different subgroups with distinct cuproptosis-based molecular patterns. Analyses of clinical significance, long-term survival, and immune features were performed on subgroups accordingly. The cuproptosis-based risk signature and nomogram were constructed and validated relying on the ccRCC cohort as well. The cuproptosis scoring system was generated to better characterize ccRCC patients. Finally, in vitro validation was conducted using ccRCC clinical samples and cell lines.ResultPatients from different subgroups displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related score, and therapeutic responses. The prognostic model and cuproptosis score were well validated and proved to efficiently distinguish the high risk/score and low risk/score patients, which revealed the great predictive value. The cuproptosis score also tended out to be intimately associated with the prognosis and immune features of ccRCC patients. Additionally, the hub cuproptosis-associated gene (CAG) FDX1 presented a dysregulated expression pattern in human ccRCC samples, and it was confirmed to effectively promote the killing effects of copper ionophore elesclomol as a direct target. In vitro functional assays revealed the prominent anti-cancer role of FDX1 in ccRCC.ConclusionCuproptosis played an indispensable role in the regulation of TME features, tumor progression, and long-term prognosis of ccRCC.

Most spatial models include a spatial weights matrix (W) derived from the first law of geography to adjust the spatial dependence to fulfill the independence assumption. In various fields such as epidemiological and environmental studies, the spatial dependence often shows clustering (or geographic discontinuity) due to natural or social factors. In such cases, adjustment using the first-law-of-geography-based W might be inappropriate and leads to inaccuracy estimations and loss of statistical power. In this work, we propose a series of data-driven Ws (DDWs) built following the spatial pattern identified by the scan statistic, which can be easily carried out using existing tools such as SaTScan software. The DDWs take both the clustering (or discontinuous) and the intuitive first-law-of-geographic-based spatial dependence into consideration. Aiming at two common purposes in epidemiology studies (ie, estimating the effect value of explanatory variable X and estimating the risk of each spatial unit in disease mapping), the common spatial autoregressive models and the Leroux-prior-based conditional autoregressive (CAR) models were selected to evaluate performance of DDWs, respectively. Both simulation and case studies show that our DDWs achieve considerably better performance than the classic W in datasets with clustering (or discontinuous) spatial dependence. Furthermore, the latest published density-based spatial clustering models, aiming at dealing with such clustering (or discontinuity) spatial dependence in disease mapping, were also compared as references. The DDWs, incorporated into the CAR models, still show considerable advantage, especially in the datasets for common diseases.

Objective: To evaluate the feasibility of three bladder neck reconstruction (BNR) techniques in laparoscopic radical prostatectomy (laparoscopic RP) and their effects on urinary continence. Methods: We retrospectively analyzed 121 patients with organ-confined prostate cancer, who underwent laparoscopic RP in our center from March to December 2018. Three BNR techniques-zero o'clock reconstruction (ZOR), six o'clock reconstruction (SOR), and three/nine o'clock reconstruction (T/NOR)-applied in patients with large bladder opening after prostate resection are described comprehensively. Demographic and perioperative data were collected and analyzed using Pearson's chi-square and one-way analysis of variance test. Multivariate analysis was performed to explore predictors that affected continence recovery in 24 hours, 1 month, 3 months, and 6 months after catheter removal. Results: Laparoscopic RP was performed in all patients, wherein 37, 35, 34, and 15 patients underwent bladder neck preservation, ZOR, SOR, and T/NOR techniques, respectively. There were more high-risk patients and larger mean prostate volume in groups with BNR techniques. Perioperatively, patients with reconstruction techniques had longer operation and anastomosis time, more estimated blood loss, and more positive margin status. Nevertheless, there was no significant difference among four groups regarding continence recovery in 24 hours, 1 month, 3 months, and 6 months after catheter removal. On multivariable analysis, positive apical margin and long anastomosis time were independent adverse predictors of continence recovery in 24 hours. Large prostate volume and positive apical margin were adverse factors of continence recovery at 1, 3, and 6 months. Conclusion: Three different kinds of BNR techniques were safe and feasible in laparoscopic RP and had no different impact on continence recovery. Positive apical margin, large prostate volume, and long anastomosis time were independent adverse predictors of continence.

Purpose The ongoing coronavirus disease 2019 (COVID-19) epidemic increasingly threatens the public health security worldwide. We aimed to identify high-risk areas of COVID-19 and understand how socioeconomic factors are associated with the spatial distribution of COVID-19 in China, which may help other countries control the epidemic. Methods We analyzed the data of COVID-19 cases from 30 provinces in mainland China (outside of Hubei) from 16 January 2020 to 31 March 2020, considering the data of demographic, economic, health, and transportation factors. Global autocorrelation analysis and Bayesian spatial models were used to present the spatial pattern of COVID-19 and explore the relationship between COVID-19 risk and various factors. Results Global Moran’s I statistics of COVID-19 incidences was 0.31 (P Conclusion Our results suggested that COVID-19 risk was positively associated with the level of economic development and population movements. Blocking population movement and reducing local exposures are effective in preventing the local transmission of COVID-19.

Background Centenarians represent an intriguing model for healthy aging. They appear to have adapted well to their lives and are likely to be influenced by previous lifestyle habits, and their life satisfaction is influenced by mental and psychological health. Objective The aim of this study is to explore centenarians’ lifestyles by sex and their potential contribution to life satisfaction. Method In order to examine the common characteristics of centenarians in Hainan and the potential differences between men and women, a cross-sectional survey was conducted with 223 cognitively-intact Chinese centenarians. We also explored the association between life satisfaction and other physical factors using binary logistic regression and principal component analysis. Results The results provided supplementary evidence indicating that women tended to live longer than men. However, the difference in life satisfaction observed between the sexes was not obvious (p = 0.659). The proportion of physical factors between each sex showed a similar trend in distribution. Most centenarians’ lifestyles were similar, in that they followed a light diet and did not smoke or drink alcohol. Centenarians in better physical condition and with higher self-assessment, as well as those with “alcohol and tobacco habits,” were more satisfied with their life. Of the factors examined in the binary logistic regression, sleep satisfaction was the only factor significantly positively correlated with life satisfaction (p Conclusion The research findings elucidated physiological and psychological health in centenarians and provided a model of healthy aging strategies for reference purposes.

Cerebral venous sinus thrombosis (CVST) is a rare ischemic cerebrovascular disease. The aim of this retrospective observational study was to investigate the risk factors for complication of cerebral venous sinus thrombosis by seizures and to explore the impact of such seizures on clinical outcomes. Patients with cerebral venous sinus thrombosis with or without epileptic seizures were retrospectively analyzed and compared in terms of clinical variables, causative factors, clinical presentation, and imaging data. In all, 69 patients with cerebral venous sinus thrombosis were enrolled in this study, 32 (46.38%) of whom had experienced secondary seizures. Compared with those with no seizures, significantly more patients with secondary seizures had hemiplegia (37.50 vs. 15.63%; P = 0.020), bleeding (29.40 vs. 10.81%; P = 0.047), lesions involving the frontal (31.25 vs. 10.81%; P = 0.023) and temporal lobe (43.75 vs. 8.11%; P = 0.005), and thrombosis in the superior sagittal sinus (65.63 vs. 40.54%; P = 0.036). Multivariate logistic regression analysis showed focal neurological deficits (P = 0.004, odds ratio = 5.16, 95% CI 1.99–15.76) and thrombosis of the superior sagittal sinus (P = 0.039, odds ratio = 0.13, 95% CI 0.04–0.37) were independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis. In addition, mortality rate (9.38 vs. 5.41%; P = 0.469) and 90-day excellent prognosis rate (81.25 vs. 86.47%; P = 0.793) did not differ significantly between patients with and without epileptic seizures. The presence of focal neurological deficits and thrombosis of the superior sagittal sinus are independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis, whereas mortality and 90-day prognosis have no correlation with secondary seizures.

// Yiyang Liu 1, * , Jian Qian 1, * , Xiao Li 1, * , Wei Chen 1 , Aiming Xu 1 , Kai Zhao 1 , Yibo Hua 1 , Zhengkai Huang 1 , Jianzhong Zhang 1 , Chao Liang 1 , Shifeng Su 1 , Pu Li 1 , Pengfei Shao 1 , Jie Li 1 , Chao Qin 1 , Zengjun Wang 1 1 Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Zengjun Wang, email: zengjunwang@njmu.edu.cn Chao Qin, email: qinchao@njmu.edu.cn Keywords: lncRNA BX357664, long noncoding RNA (LncRNA), epithelial-to-mesenchymal transition, TGF-beta 1/p38/HSP27 signaling, renal cell carcinoma Received: December 06, 2015 Accepted: September 12, 2016 Published: October 27, 2016 ABSTRACT Antisense long noncoding RNAs (lncRNAs) are reported to play a regulating role in carcinogenesis of various human malignancies. However, the function of lncRNAs and their underlying mechanism in renal cell carcinoma (RCC) is still unknown. The aims of this study are to investigate the expression of lncRNA BX357664 in RCC and to explore its function in RCC cell lines. As a result, BX357664 was downregulated in RCC according to previous microarray analysis and qualitative real-time polymerase chain reaction. After the upregulation of BX357664, reduced migration, invasion, and proliferation capabilities in RCC cells were detected. Furthermore, Western blot analysis was conducted to identify the influence of BX357664 on epithelial-to-mesenchymal transition, matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor-beta 1 (TGF-β1)/p38/HSP27 signaling pathway in RCC. Subsequently, upregulating the protein level of TGF-β1 in the presence of BX357664 could rescue the suppression of the malignant behavior mediated by BX357664, indicating that BX357664 attributed its inhibitory role to the suppression of TGF-β1. Therefore, we investigated a novel lncRNA BX357664, which might exhibit its inhibitory role in RCC metastasis and progression by blocking the TGF-β1/p38/HSP27 pathway.

To evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) for treating urinary retention in patients with advanced prostate cancer. Thirty-eight cases of advanced prostate cancer with urinary retention were enrolled in this retrospective study. All the 38 patients were treated with CAB as a basis. Among them, 21 cases chose HoLEP additionally (HoLEP group). Seventeen cases stuck to CAB alone (CAB group). Serum PSA level, International Prostate Symptom Score (IPSS), quality of life score (QoLs), maximal flow rate (Qmax), and post-void residual volume (PVR) at 3, 6, 12, and 18 months after treatment were comparatively analyzed. The perioperative and postoperative parameters of HoLEP were assessed. Both groups demonstrated significant improvement in IPSS, QoLs, Qmax, and PVR during follow-up. But these parameters of HoLEP group improved more rapidly, significantly, and durably than CAB group. No serious complications were observed during and after HoLEP. PSA level of patients in both groups declined dramatically after surgery. But PSA in HoLEP group showed more dramatic and continuous drop. Besides, 1 of 21 patients in HoLEP group transferred into castration-resistant prostate cancer (CRPC) at 18th month of follow-up. While in CAB group, 5 of 17 patients developed into CRPC at 12th month of follow-up (P = 0.02 < 0.05). HoLEP was minimally invasive, safe, and effective, and could serve as a palliative approach to rapidly restore the patients' urine and play a cytoreductive role in advanced PCa to improve the oncological prognosis.

Laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping has become an important method to minimize the warm ischemia of the kidney during the surgery. In the present study, we adopted a new model of calculating surgery-related kidney volume loss (SKVL), which was derived from the imaging technology to predict the outcomes of LPN with segmental renal artery clamping. A total of 111 consecutive patients underwent LPN with available pre- and post-operation computed tomography (CT) scanning data were retrospectively analyzed. The SKVL was calculated using the parameter derived from the CT scan. The correlation between the SKVL and the perioperative outcomes as well as the renal function loss was estimated by the logistic regression analyses. The mean SKVL was 8.99 cm3; kidney volume and tumor volume was 147.48 cm3 and 25.87 cm3, respectively. The SKVL was associated with maximum diameter of tumor (P = 0.001), tumor volume (P

Objective To investigate factors that may predict successful precise segmental artery clamping during retroperitoneal laparoscopic partial nephrectomy (LPN) for treatment of T1 kidney tumor. Patients and Methods Patients with clinical T1 tumors (n = 248) who received retroperitoneal LPN from June 2012 through February 2018 were reviewed, including demographics and clinical features. However, only 225 cases (90.7%) were available to analyze. Precise segmental artery clamping was the first clamping method selected during the LPN. If unsuccessful, conversion to main renal artery clamping was conducted. The perioperative features and functional outcomes of the 2 clamping types were compared. Results Of the 225 patients, 190 procedures were effectively performed using segmental artery clamping, while 35 (15.6%) were converted to main renal artery clamping. None were converted to open surgery. Clamping the main renal artery was associated with longer operative time, less estimated blood loss, and higher glomerular filtration rate reduction, compared with successful segmental artery clamping. Univariable analyses determined that the following features affected the feasibility of segmental artery clamping: gender; hypertension; tumor location, growth pattern, and targeted artery number; R.E.N.A.L. nephrometry score (RNS); and Mayo adhesive probability (MAP) score. The multivariable analyses indicated that male gender, high RNS, and elevated MAP score were independent factors lowering the viability of segmental artery clamping. Conclusion LPN with segmental artery clamping is generally safe for removing T1 kidney tumors. Extra cognizance may be required in men and cases with high RNS or MAP score.

Background Delayed bowel function recovery and postoperative ileus are relatively serious complications of laparoscopic radical cystectomy (LRC). Our study aimed to determine whether performing pelvic re-peritonealization reduces the incidence of these complications. Methods Clinical data of 78 patients who had undergone LRC with pelvic re-peritonealization from August 2015 to December 2017 were retrospectively collected and compared with those of 92 patients who had undergone LRC alone between January 2013 and July 2015 in our institution. Differences in duration of surgery, estimated blood loss, time to recovery of bowel function, the complications of intestinal and blood vessel injury, and incidence of postoperative ileus between the two groups were analyzed. Results Baseline characteristics such as age, sex and BMI were balanced between the two groups. There were no significant differences in duration of surgery (P = 0.072), estimated blood loss (P = 0.717), or incidence of intestinal obstruction (P = 0.225) between the two groups. Interestingly, patients who had undergone pelvic re-peritonealization recovered bowel function more rapidly than those had not (2.79 d vs. 3.72 d, P = 0.001). Additionally, hospitalization stay was significantly shorter for patients with re-peritonealization than for those without (5.46 d vs. 6.68 d, P = 0.029). Conclusions Compared with LRC alone, LRC with pelvic re-peritonealization as described in the present study had comparable perioperative complications, but was associated with more rapid gastrointestinal recovery and shorter hospitalization stay.

To assess the feasibility and safety of a modified retroperitoneoscopic technique in supine position for the primary tumors located below the level of renal pedicle.In this retrospective study, 27 patients with primary retroperitoneal tumors located below the level of renal pedicle were recruited from January 2009 till now. The mean age of patients was 49.0 years (36-66 years). The average body mass index was 21.1 ± 1.4 kg/m(2). The retroperitoneoscopic resections were performed in supine position for all patients. The perioperative outcomes were collected and analyzed.All cases were performed by the modified technique without converting to open surgery. The mean operation time was 98.3 ± 12.8 min, with a mean estimated blood loss of 94.4 ± 42.5 mL. There were four patients suffering from intraoperative complications, one with the inferior vena cava (IVC) injury, one with the lumbar vein injury, and other two with the peritoneum breach. Postoperatively, the median bowel recovery time was 2 days (range: 1-3 days), and the mean length of stay after operation was 2.9 ± 1.0 days. Additionally, compared with the tumors located around the aorta (region B), a longer operation time was needed with tumors located around the IVC (region A) (A vs B: 105.8 ± 10.2 vs 91.2 ± 14.4, p = 0.02). Histopathology confirmed paraganglioma in 5 cases, schwannoma in 10 cases, and ganglioneuroma in 12 cases. After follow-up of 12-72 months, no recurrences have been identified.Our modified retroperitoneoscopic technique in supine position was proven to be safe and effective for the treatment of primary retroperitoneal tumors, especially suitable for the tumors located below the level of the renal pedicle.

Renal cell carcinoma (RCC) is one of the most common malignant tumors in the urinary system, whose molecular mechanism is still not clear. ALPK2 is a member of alpha protein kinase family, and its relationship with RCC is never reported. In this study, expression of ALPK2 in tumor tissues or cells of RCC was detected by qPCR, western blotting and immunohistochemical analysis. The effects of ALPK2 knockdown on cell proliferation, colony formation, cell migration and apoptosis were assessed by MTT, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of ALPK2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. The results demonstrated that ALPK2 was upregulated in tumor tissues of RCC and its high expression was significantly associated with advanced stage and poor prognosis. Knockdown of ALPK2 could inhibited cell proliferation, colony formation and cell migration of RCC cells, while promoting cell apoptosis. The suppression of tumor growth in vivo by ALPK2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of RCC by ALPK2 may involve Akt, CDK6, Cyclin D1 and PIK3CA signaling. Therefore, our studies suggested that ALPK2 may act as a tumor promotor in the development and progression of RCC, and could be considered as a novel therapeutic target for RCC treatment.

Current antiobesity therapeutics are associated with side effects and/or poor long-term patient compliance, necessitating development of more efficacious and safer alternatives. Herein, we designed and engineered a new class of orally acting pharmaceutical agents, or micelle sequestrant polymers (MSPs), that could respond to the pH change in the gastrointestinal (GI) tract and potentially sequester lipid micelles; inhibiting lipid absorption through a pH-triggered flocculation process. These MSPs, derived from poly(2-(diisopropylamino)ethyl methacrylate) and poly(2-(dibutylamino)ethyl methacrylate), were soluble in acidic media, but they transitioned to become insoluble around pH 7.2 and 6.1, respectively. MSPs showed substantial bile acid and triglyceride sequestration capacity with fast pH response tested in vitro. In vivo study showed that orally dosed MSPs significantly enhanced fecal elimination of triglycerides and bile acids. Several MSPs increased fecal elimination of triglycerides by 9-10 times compared with that of the control. In contrast, fecal concentration of bile acids, but not triglycerides, was increased by cholestyramine or Welchol. Importantly, fecal elimination of bile acids and triglycerides was unaltered by addition of control dietary fibers. MSPs may serve as a novel approach to weight loss that inhibits excess caloric intake by preventing absorption of excess dietary triglycerides.

Increasing antibiotic resistance has compelled the development of novel antibiotics and adjuvant therapies that enhance the efficacy of existing antibiotics. Iron plays a critical role in bacterial infections, yet the use of iron chelators as adjuvant therapy with antibiotics has yielded highly variable outcomes. Multivalent polymeric materials offer an alternative approach to bind and sequester iron via high avidity interactions. Here, a biomimetic iron-sequestering polymer (PAI-DHBA) was synthesized by modifying side chains of cross-linked polyallylamine (cPAI) with 2,3-dihydroxybenzoic acid (DHBA). PAI-DHBA polymer gels with various DHBA contents showed high iron affinity indices and high selectivity for iron. The polymers showed mild antibiotic properties when used to treat established bacterial cultures. Pretreating culture media with PAI-DHBA polymer, however, removed all detectable iron from media and effectively inhibited the growth of Pseudomonas aeruginosa. In addition, bacterial growth was more susceptible to antibiotics combined with PAI-DHBA. Multivalent polymers that bind and sequester iron, such as PAI-DHBA, offer a promising early intervention or adjuvant to antibiotics.

Aldolase A (fructose-bisphosphate aldolase A, ALDOA) is a glycolytic enzyme that catalyzes reversible conversion of fructose‑1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. ALDOA has been revealed to be related with many carcinomas, but its expression and function in renal cell carcinoma (RCC) remain unknown. This study aimed to detect expression of ALDOA in human RCC tissue samples and to explore its function in RCC cell lines. Reverse transcription-polymerase chain reaction was used to quantify ALDOA in human RCC samples. A total of 139 RCC tissue samples obtained after surgery were analyzed in tissue microarray for ALDOA immunohistochemistry-based protein expression. Assays for cell cycle, viability, migration, and invasion were performed to assess phenotypic changes in RCC cells after ALDOA knockdown by small interfering RNA-mediated gene silencing approach and ALDOA upregulation by overexpression plasmids. Western blot analysis was used to identify alterations in markers for epithelial-mesenchymal transition (EMT), which affects metastasis and the Wnt/β‑catenin signaling pathway that influences RCC cell growth. ALDOA was upregulated in RCC samples and RCC cell lines (P

It is now recognized that solid tumors encroach on the host’s immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy. Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients’ primary malignancy. Lysate mixture was inoculated intradermally, while peripheral blood mononuclear cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post-treatment tumor-specific T-cell response and cytotoxicity was confirmed via Elispot and real-time cell analyzing (RTCA) assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration. There was a significant increase in cytotoxicity exhibited by T cells measured using both Elispot and RTCA following treatment. Correlation analysis determined significant association between higher post-treatment cytotoxicity scores and survival status (R = 0.52, p = 0.0028) as well as longer survival duration in months (R = 0.59, p = 0.005). Our treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy.

Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.

To assess the technique and short-term outcomes of laparoscopic partial nephrectomy (LPN) with precise segmental renal artery clamping for clinical T1b (cT1b) tumors and to analyze the possible factors affecting the glomerular filtration rate (GFR) reduction.This retrospective study investigated the outcomes of 72 patients with cT1b tumors who received LPN from June 2008 to May 2014. Based on three-dimensional dynamic renal vascular models built before surgery, target arteries were precisely clamped and tumors were removed under regional parenchymal ischemia. Perioperative and follow-up outcomes were analyzed.All the LPN procedures were effectively performed using the novel technique, without converting to main renal artery clamping or open surgery. The mean operative time was 86 min, with a mean warm ischemic time of 25 min. The median estimated blood loss was 200 mL (range: 80-800). The postoperative mean GFR was 64% of the preoperative baseline, and the total complication rate was 19.4%. In multivariable analyses, the two independent factors affecting postoperative GFR were the RENAL nephrometry score (RNS) and number of intraoperative clamped segmental arteries. The median follow-up was 24 months (range: 6-72). The overall, recurrence-free, and cancer-specific survival rates were 100%, 95.8%, and 100%, respectively.For patients with cT1b tumor, LPN with precise segmental renal artery clamping is safe and feasible for removing tumors and preserving the blood supply and normal renal parenchyma. Short-term oncologic and functional outcomes were satisfactory. Postoperative GFR was related to the preoperative RNS and number of intraoperative clamped segmental arteries.

Aberrant microRNAs (miRNAs) are reported to contribute to the pathogenesis of most human malignancies. The miRNA, miR-134, has been found to be downregulated in renal cell carcinoma (RCC), but its function in the disease is unknown. The aims of this study were to detect the expression of miR-134 in human RCC samples and explore its function in RCC cell lines. Real-time qualitative polymerase chain reaction (qPCR) was used to quantify miR-134 in human RCC samples. Assays for cell cycle, viability, migration, and invasion were performed to assess the phenotypic changes in RCC cells. A luciferase reporter assay was carried out to confirm whether KRAS (Kirsten rat sarcoma viral oncogene homolog) is a direct target of miR-134. Western blot was used to identify the potential signaling pathways that had an impact on RCC cell growth and alterations of markers for epithelial–mesenchymal transition (EMT), which affected metastasis by miR-134. miR-134 was found to be downregulated in RCC samples (p

Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.

BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC. METHODS: A total of 5 tagging single-nucleotide polymorphisms (tSNPs) in RKIP were selected and genotyped by SNapShot method in a case-control study of 859 RCC patients and 1004 controls. The logistic regression was used to evaluate the genetic association with occurrence and progression of RCC. The functionality of the important SNP was preliminary examined by qRT-PCR. RESULT: We found that the rs17512051 in the promoter region of RKIP was significantly associated with decreased clear cell RCC (ccRCC) risk (TA/AA vs. TT: P = 0.039, OR = 0.78, 95%CI = 0.62-0.99). Another SNP (rs1051470) in the 3'UTR region of RKIP was marginally associated with increased ccRCC risk (TT vs. CC+CT: OR = 1.45, 95%CI = 1.01-2.09). In the stratified analysis, the protective effect of rs17512051 was more predominant in the subgroups of male, non-smokers, non-drinkers as well as subjects without history of diabetes. Furthermore, we observed higher RKIP mRNA levels in the presence of the rs17512051A allele in normal renal tissues. CONCLUSION: Our results suggest that the potentially functional RKIP rs17512051 polymorphism may affect ccRCC susceptibility through altering the endogenous RKIP expression level. Risk effects and the functional impact of this polymorphism need further validation.

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are members of the insulin-like growth factor (IGF) family that play important roles in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese population. This hospital-based case-control study included 664 PCa patients and 702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the TaqMan assay. The genetic associations between the pathogenesis and progression of PCa were assessed by logistic regression. We found that the genotype and allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly different when comparing PCa cases to controls (P = 0.005, 0.005 and 0.020, respectively). In the combined analysis, individuals with 2-6 risk alleles had an elevated risk of PCa compared to those with 0-1 risk alleles. We also found that the association between the combined risk alleles and the risk of PCa appeared stronger in the following subgroups: individuals older than 71 years of age (OR = 1.41, 95%CI = 1.05-1.91, P = 0.020), nonsmokers (OR = 1.68, 95%CI = 1.21-2.32, P = 0.002), nondrinkers (OR = 1.32, 95%CI = 1.02-1.61, P = 0.002), and those with a negative family history of PCa (OR = 1.28, 95%CI = 1.02-1.71, P = 0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612) and the joint genotypes with 2-6 risk alleles, may contribute to the susceptibility to PCa, but not the progression, in the Chinese population.

Background Recent large-scale transcriptome analyses have found large numbers of transcripts, including that of long non-coding RNAs (lncRNAs), which are aberrant in various diseases, especially cancers. However, it is not clear whether lncRNAs are involved specifically in renal cell carcinoma (RCC). We investigated the expression patterns of lncRNAs in five RCC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via microarray. Methods A microarray with 33,045 lncRNA probes and 30,215 mRNA probes was used to identify deregulated lncRNAs in five RCC patients. Furthermore, we confirmed the relative expression levels of AK096725 and ENST00000453068 in 70 paired samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results The lncRNA microarray revealed 27,279 lncRNAs in RCC samples, of which 480 were significantly upregulated (P1.5) and 417 were significantly downregulated (P1.5) compared with the matched non-tumor samples. In addition, 19,995 mRNAs were detected, of which 458 were significantly upregulated (P1.5) and 413 were significantly downregulated (P1.5). The expression level changes of AK096725 (P = 0.043) and ENST00000453068 (P

To analyze the characteristic of changes in extravascular lung water index (EVLWI) of H7N9 avian influenza patients who complicated with acute respiratory distress syndrome (ARDS), and to approach the relevance between EVLWI and severity, pulmonary oxygenation in patients with lung injury.Four H7N9 avian influenza patients administered from April to June in 2013 in First Affiliated Hospital of Nanchang University were studied. The patients who suffered from severe ARDS were administered with low tide volume ventilation plus positive end-expiratory pressure (PEEP), namely protected ventilation strategy, with monitoring hemodynamic parameters and EVLWI through pulse-indicated continuous cardiac output (PiCCO) catheter. During ventilation, patients' parameters, such as PEEP, fraction of inspired oxygen (FiO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), EVLWI, and central venous pressure (CVP) were collected.All 4 H7N9 avian influenza patients were complicated with ARDS, 2 patients were classified to severe ARDS and administered with comprehensive therapies, specially protected ventilation strategy; ventilation duration was 9 days and 30 days respectively, and PiCCO monitoring was 9 days and 21 days respectively. EVLWI of 2 patients on the 1st, 2nd, 3rd day was 10.0±3.2 ml/kg, 12.0±2.9 ml/kg, 14.0±4.2 ml/kg, and 24.0±6.7 ml/kg, 24.0±6.1 ml/kg, 23.0±5.8 ml/kg, respectively. As their conditions became better, patients' EVLWI decreased to 5.5±2.7 ml/kg and 7.0±3.0 ml/kg, respectively at weaning. PEEP and FiO2 of 2 patients were down-regulated, PaO2/FiO2 increased to 334±64 mm Hg and 142±53 mm Hg at weaning. However, no significant changes in CI, SVRI, PVRI and CVP in the 2 patients were observed.EVLWI increases when H7N9 avian influenza patients are complicated with severe ARDS. As the conditions get better, EVLWI returns to normal value gradually. There is relevance between the motive changes in EVLWI and severity of ARDS and pulmonary oxygenation.

To investigate the combined effects between the two polymorphisms murine double minute 2 (MDM2) rs2279744 T→G and P53 rs1042522 G→C on the genetic susceptibility of breast cancer.A total of 600 female patients with diagnosed breast cancer were consecutively recruited from the Yuhang district, Hangzhou city during March 2001 to May 2009. In the same period as the cases were collected, 600 healthy women living in Yuhang district, Hangzhou city were selected from a nutritional survey conducted. Peripheral blood lymphocytes were obtained from the study subjects and the demographic information were collected through questionnaires. PCR-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping MDM2 rs2279744 T→G and P53 rs1042522 G→C. Logistic regression analysis was used to analyze the combined effects of the two polymorphisms on breast cancer risk.The frequency of MDM2 rs2279744 GG, TG and TT genotypes were 31.5% (189/600), 45.5% (273/600), 23.0% (138/600) in case group and 19.0% (114/600), 49.2% (295/600), 31.8% (191/600) in control group. The frequency of P53 rs1042522 GG, GC and CC genotypes were 23.1% (139/600), 50.2% (301/600), 26.7% (160/600) in case group and 30.5% (183/600), 51.3% (308/600), 18.2% (109/600) in control group. Logistic regression analysis showed that carriers with rs2279744 TG, GG genotypes had a significant increased risk for developing breast cancer compared with rs2279744 TT carriers (OR = 1.31, 95%CI: 0.97 - 1.73 for TG; OR = 2.24, 95%CI: 1.61 - 3.09 for GG). When comparing with rs1042522 GG carriers, carriers with rs1042522 GC, CC genotypes had a significant increased risk for developing breast cancer (OR = 1.34, 95%CI: 0.94 - 1.68 for GC; OR = 1.89, 95%CI: 1.35 - 2.68 for CC). The united analysis of this two polymorphisms showed that compared with individuals carrying rs2279744 TT and rs1042522 GG (the frequency were 4.8% (29/600) in case group and 11.5% (69/600) in control group), carries with rs2279744 TG/GG and rs1042522 GC/GG genotypes (the frequency were 95.2% (571/600) in case group and 88.5% (531/600) in control group) showed significant higher risk in the susceptibility to breast cancer (OR = 2.30, 95%CI: 1.39 - 3.82 for TG/GC + GG; OR = 2.14, 95%CI: 1.29 - 3.55 for TT + GC/CC; OR = 2.86, 95%CI: 1.80 - 4.53 for TG/GG + GC/CC). The combination of MDM2 rs2279744 T→G and P53 rs1042522 G→C contributed to a significantly higher risk of breast cancer than did any one of the variant (P = 0.046). The risk of susceptibility to breast cancer was much higher when this two polymorphisms both variant.The MDM2 rs2279744 T→G and P53 rs1042522 G→C may be risk factor for breast cancer. Significant combined effects between the two polymorphisms may contribute to the genetic susceptibility to breast cancer.

Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1060 cases and 1225 controls from 7 published case-control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A12A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and the risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1 2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.

Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject.A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed.A total of 12 (two randomized controlled trials, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results.The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

Background The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. Methods A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I2 test. Results Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03–1.18, I2 = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06–1.39, I2 = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04–1.18, I2 = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09–1.59, I2 = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04–1.21, I2 = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05–1.21, I2 = 25.3%). Conclusions The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

A new generation of siRNA nanocarrier with compact, uniform size and excellent colloidal stability has been developed by combining inorganic nanoparticles with rationally designed triblock copolymers. In contrast to conventional cationic polymers and nanoparticles that often condense oligonucleotides into polydisperse aggregates, our nanoparticle-polymer complexes remain single after loading with siRNA. More importantly, they are highly stable even in complete serum, which fills the gap between in vitro technology development using serum-free (or low percentage serum) cell culture media and downstream in vivo applications. Targeted delivery is achieved in GFP-expressing HeLa cells by functionalizing the siRNA delivery vehicle with an integrin-specific peptide ligand. The GFP positive cell population can be reduced from the original 86% to 60% and 25% for non-targeted and targeted nanoparticle-polymer complexes, respectively. At the nanocarrier concentration for siRNA delivery, virtually no cytotoxicity was detected. Further development and validation of this technology by introducing biodegradable and biocompatible core particles and testing them in lab animals could enable widespread uses of siRNA and potentially lead to clinical translation.

To evaluate the efficacy of early continuous high-volume-hemofiltration in the treatment of patients with severe acute pancreatitis (SAP).Based on the method of prospective, randomized and controlled clinical trial, 60 patients with SAP between January 2005 and July 2011 from the First Affiliated Hospital of Nanchang University were divided into control group and hemofiltration group. The hemofiltration group was treated with early continuous high-volume-hemofiltration and not in the control group. The changes of vital signs, clinical symptoms and laboratory indicators were compared between the two groups before and after the treatment.After hemofiltration, the clinical symptoms such as abdominal pain, fever, tachycardia and respiratory distress in hemofiltration group were significantly remitted compared to those in the control group (P0.05). The APACHEIIscore (13.3 ± 1.0 vs 14.1 ± 1.2) and the level of TBil [(20.4 ± 11.3) µmol/L vs (28.1 ± 10.9) µmol/L], creatinine [(178.7 ± 71.8) µmol/L vs (215.6 ± 51.3) µmol/L], blood urea nitrogen [(10.1 ± 5.6) mmol/L vs (13.2 ± 3.8) mmol/L] and ALT [(51.3 ± 13.2) U/L vs (62.5 ± 14.3) U/L] were decreased compared to those in the control group (all P values0.05). The level of PaO2/FiO2 (197.3 ± 32.4 vs 178.3 ± 31.7) was increased (P0.05). After hemofiltration, heart rate was decreased gradually (P0.05) in the hemofiltration group than in the control group. Mean artery pressure (mAP) increased gradually (P0.05) in the hemofiltration group than in the control group.Early continuous high-volume-hemofiltration has significant effects on the treatment of SAP including the improvement of clinic symptoms, the blockade of development from systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS), improvement of organ function and prevention from the complications. It may become one of the important therapies for SAP.

BACKGROUND: Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks. METHODS: A meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS: The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14-1.21; for GSTT1: OR = 1.16; 95%CI = 1.11-1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19-3.24; for GSTT1: OR = 2.46; 95%CI = 1.83-3.32, respectively). CONCLUSIONS: These findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.

To explore the effect of the heating humidifier with heating wire in pipeline in patients with tracheal intubation.The present research was a prospective study. One hundred and twenty patients with tracheal intubation and mechanical ventilation who could not reach the indication of extubation after weaning were randomly divided into two groups. The patients in the control group (n = 60) were treated by routine airway management which was intermittent airway instillation with normal saline to humidify the airway, and those in the experimental group(n = 60) were used heating humidifier with heating wire in pipeline for airway humidification. The temperature and humidity of inhaled gas, sputum viscosity, the number of tracheal catheter with sputum scab after extubation, as well as number of reintubated cases due to tube plugging, and the oxygenation index at different time points after oxygen inhalation were recorded.The temperature and humidity of inhaled gas in experimental group were higher than those in control group [temperature (centigrade): 36.9 ± 0.2 vs. 22.3 ± 2.1, humidity (mg/L): 44.0 ± 2.0 vs. 27.0 ± 4.0, both P0.01]. The number of sputum viscosity II (humidification in well) in experimental group was significantly more than that in the control group (49 vs. 15), but the number of sputum viscosity III (humidification in sufficient) in experimental group was significantly less than that in the control group (8 vs. 43, both P0.05). The number of tracheal catheter with sputum scab after extubation (5 cases) and reintubation for tracheal catheter plugging (0 case) in experimental group were significantly less than those in the control group (24 cases, 6 cases, P0.01). The oxygenation index (mm Hg, 1 mm Hg = 0.133 kPa) in experimental group was increased after oxygen inhalation, and higher than that in control group at 96 hours and 120 hours (96 hours: 349.0 ± 21.3 vs. 290.0 ± 20.7, 120 hours: 354.0 ± 25.6 vs. 309.0 ± 22.6, both P0.01).The humidify of heating humidifier with heating wire in pipeline for airway humidification in patients with tracheal intubation was better than that of intermittent airway instillation with normal saline.

Protein–protein interactions (PPIs) mediated by the polo-box domain (PBD) of polo-like kinase 1 (Plk1) serve important roles in cell proliferation. Critical elements in the high affinity recognition of peptides and proteins by PBD are derived from pThr/pSer-residues in the binding ligands. However, there has been little examination of pThr/pSer mimetics within a PBD context. Our current paper compares the abilities of a variety of amino acid residues and derivatives to serve as pThr/pSer replacements by exploring the role of methyl functionality at the pThr β-position and by replacing the phosphoryl group by phosphonic acid, sulfonic acid and carboxylic acids. This work sheds new light on structure activity relationships for PBD recognition of phosphoamino acid mimetics.

In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide, PLHSpT using oxime-based post-solid-phase peptide diversification of the N-terminal Pro residue. This allowed us to achieve up to two orders-of-magnitude potency enhancement. An X-ray crystal structure of the highest affinity analogue in complex with Plk1 PBD revealed new binding interactions in a hydrophobic channel that had been occluded in X-ray structures of the unliganded protein. This study represents an important example where amino acid modification by post solid-phase oxime ligation can facilitate the development of protein-protein interaction inhibitors by identifying new binding pockets that would not otherwise be accessible to coded amino acid residues.

To investigate the organ protective effect of early continuous HVHF in patients with MODS complicated by AKI.117 patients requested HVHF in ICU due to MODS/AKI were enrolled from June 2006 to June 2011 for clinical data collection. The patients were categorized, by RIFLE scale (R-risk of renal dysfunction, I-injury to the kidney, F-failure of kidney, L-loss of kidney function, E-end stage kidney disease), into three groups: RIFLE-R (n = 15), RIFLE-I (n = 23) and RIFLE-F (n = 79). The values of their serum creatinine (SCr), oxygenation index (PaO(2) /FiO(2) ), extravascular lung water index (EVLWI), blood lactic acid (Lac), prothrombin time (PT), aspartate aminotransferase (AST), acute physiology and chronic health evaluation II (APACHE II) score were recorded, at the beginning of, and within 72 hours after HVHF. The 90-day survival rate in each group was calculated.No significant difference was found between RIFLE-R and RIFLE-I group, within 72 hours after HVHF, in SCr, PaO(2) /FiO(2) , EVLWI, Lac, PT, AST, or APACHE II score. The mean values of SCr, EVLWI, Lac, PT, AST, APACHE II score, within 72 hours after HVHF in the RIFLE-F group were significantly higher in comparison with RIFLE-R, and RIFLE-I group [SCr (μmol/L): 260.50±35.51 vs. 83.61±21.07, 89.71±23.81 ; EVLWI (ml/kg): 12.18±2.11 vs. 10.94±1.50,10.76±1.92; Lac (mmol/L): 2.40±0.56 vs. 1.58±0.27, 1.68±0.35; PT (sec): 14.14±1.50 vs. 12.67±1.18, 12.51±0.94; AST (U/L): 96.19±18. 84 vs. 47.91±12.85, 56.39±13.44; APACHE II score: 20.17±2.61 vs. 17.79±2.65, 18.53±2.87, P0.05 or P0.01]; However, the PaO(2) /FiO(2) (mm Hg, 1 mm Hg = 0.133 kPa) value in RIFLE-F group was found significantly lower compared to RIFLE-R and RIFLE-I group (202.80±19.07 vs. 245.24±21.18, 250.63±25.56, P0.01). No statistical significant difference was found in the 90-day survival rate among RIFLE-R, RIFLE-I and RIFLE-F group (66.67%, 65.22%, 63.29%, respectively, P0.05).Early HVHF has protective effect against organs injury in patients with MODS and AKI.

A mutation in MEF2A (myocyte enhancer factor-2A) had been reported to be the first gene linked directly to coronary artery disease (CAD). However, an opposing opinion was proposed recently that MEF2A mutations are not a common cause of sporadic CAD. In this study, we screened exon 11 of the MEF2A gene in people of the Han nationality in China and finished some functional analysis of found variations.A gene structural investigation of MEF2A in 257 CAD patients and 154 control individuals were developed in this study. Subsequently, typical MEF2A variations were cloned and expressed in HeLa or 293T cell line to illustrate whether found structure changes could influence the main biological functions of these proteins. At last, another set of gene structural screen was initialized to get more reliable conclusions.Totally 16 different variations were detected in exon 11 of this gene in the first set of gene structural screen. By cloning and expressing typical MEF2A proteins in cultured cells, all the acquired MEF2A variations had transcriptional activation capabilities and subcellular localization patterns similar to those of the wild-type protein. Further larger scale genetic screening also revealed that the reported genetic variations of MEF2A did not differ significantly between CAD patients and healthy controls.Our results reveal that structural changes of exon 11 in MEF2A are not involved in sporadic CAD in the Han population of China.

Objective To analyze the value of the hCG ratio of peritoneal serum versus venous serum (RP/V) for early diagnosis and prognostic evaluation of ectopic pregnancy (EP). Design Retrospective clinical study. Setting University hospital. Patient(s) One hundred three women with hemoperitoneum and positive urine hCG tests underwent laparoscopy or laparotomy. Intervention(s) Venous serum and peritoneal serum samples were obtained; ultrasound was performed in all the patients; dilatation and curettage was used in 28 patients. Main Outcome Measure(s) Quantitative hCG and RP/V. Result(s) The RP/V in EP (5.55 ± 4.32) is apparently greater than that in hemoperitoneum with intrauterine pregnancy (hIUP; 0.61 ± 0.18). The median RP/V is 4.07 in the EP group versus 0.60 in the hIUP group, with a suggested threshold value of 1.0 for their differential diagnosis. Moreover, the RP/V of EP shows the dominant difference between the patients with active bleeding (8.03 ± 3.29, n = 24) and the patients without active bleeding (4.59 ± 3.88, n = 16) when the hCG level of venous serum is more than 1500 U/L. Conclusion(s) RP/V could instantly diagnose ectopic pregnancy and differentiate it from hIUP.

To study the histopathologic features, differential diagnosis and pathogenesis of diabetic cardiomyopathy.The clinicopathologic features of 40 autopsy cases of diabetes mellitus were studied. The hearts from another 40 cases of non-diabetic elderly deceased were used for comparison.In the 40 cases of diabetes studied, 36 cases (90.0%) showed microscopic myocardial cell death. Focal interstitial fibrosis was observed in 37 cases (92.5%). On the other hand, similar myocardial cell death and patchy interstitial fibrosis was seen in 8 cases (20.0%) and 9 cases (22.5%) of non-diabetic hearts, respectively. The difference between the two groups was statistically significant (P0.01). The mural thickness of intramyocardial blood vessels was significantly increased in diabetic group (20.6 microm +/- 4.2 microm) than in non-diabetic group (7.2 microm +/- 5.2 microm), P0.01.The myocardial changes in diabetic group however were similar to those in non-diabetic group with systemic hypertension.Pathologic diagnosis of diabetic cardiomyopathy relies on detailed histologic examination of heart tissue and clinical correlation of a long history of diabetes mellitus. Exclusion of other possible etiologies is also essential. The myocardial cell death observed may be due to the ischemic effect induced by diabetic microangiopathy in cardiac muscle.

To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis.The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed.The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed.The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.

AIM: To evaluate preoperative double-balloon enteroscopy for determining bleeding lesions of small intestine, thus directing selective surgical intervention. METHODS: We retrospectively reviewed 56 patients who underwent double-balloon enteroscopy to localize intestinal bleeding prior to surgical intervention, and compared enteroscopic findings with those of intraoperation to determine the accuracy of enteroscopy in identifying and localizing the sites of small intestinal bleeding. RESULTS: Double-balloon enteroscopy was performed in all 56 patients in a 30-mo period. A possible site of blood loss was identified in 54 (96%) patients. Enteroscopy provided accurate localization of the bleeding in 53 (95%) of 56 patients, but failed to disclose the cause of bleeding in 4 (7%). There was one case with negative intraoperative finding (2%). Resection of the affected bowel was carried out except one patient who experienced rebleeding after operation. Gastrointestinal stromal tumor (GIST) was most frequently diagnosed (55%). CONCLUSION: Double-balloon enteroscopy is a safe, reliable modality for determining bleeding lesion of small intestine. This technique can be used to direct selective surgical intervention.