Differential protein expression in patients with urosepsis.

PURPOSE: Urosepsis in adults comprises approximately 25% of all sepsis cases, and is due to complicated urinary tract infections in most cases. However, its mechanism is not fully clarified. Urosepsis is a very complicated disease with no effective strategy for early diagnosis and treatment. This study aimed to identify possible target-related proteins involved in urosepsis using proteomics and establish possible networks using bioinformatics. METHODS: Fifty patients admitted to the Urology Unit of Lanzhou General PLA (Lanzhou, China), from October 2012 to October 2015, were enrolled in this study. The patients were further divided into shock and matched-pair non-shock groups. 2-DE technique, mass spectrometry and database search were used to detect differentially expressed proteins in serum from the two groups. RESULTS: Six proteins were found at higher levels in the shock group compared with non-shock individuals, including serum amyloid A-1 protein (SAA1), apolipoprotein L1 (APOL1), ceruloplasmin (CP), haptoglobin (HP), antithrombin-III (SERPINC1) and prothrombin (F2), while three proteins showed lower levels, including serotransferrin (TF), transthyretin (TTR) and alpha-2-macroglobulin (A2M). CONCLUSION: Nine proteins were differentially expressed between uroseptic patients (non-shock groups) and severe uroseptic patients (shock groups), compared with non-shock groups, serum SAA1, APOL1,CP, HP, SERPINC1and F2 at higher levels, while TF, TTR and A2M at lower levels in shock groups.these proteins were mainly involved in platelet activation, signaling and aggregation, acute phase protein pathway, lipid homeostasis, and iron ion transport, deserve further research as potential candidates for early diagnosis and treatment. (The conclusion seems too simple and vague, please re-write it. You may focus at what proteins have been expressed and introduce more detail about its significance.).

[Clinical treatment of erectile dysfunction in type 2 diabeticpatients in the high-altitude area].

OBJECTIVE: To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area. METHODS: This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients. RESULTS: There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P <0.05), SIS score (3.35 ± 2.43vs6.83± 2.61and 3.41 ± 2.38 vs 4.92± 2.49, P <0.05), and penile hemodynamic parameters obtained by color duplex Doppler ultrasonography(P <0.05), with significant differences between the two groups in the IIEF-5 score (11.54 ± 7.72 vs 9.37± 1.65, P <0.05) and SIS score (6.83± 2.61 vs 4.92± 2.49, P <0.05) but not in the penile hemodynamic parameters (P >0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05). CONCLUSIONS: Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.

The explicitly correlated same number of optimized parameters (SNOOP-F12) scheme for calculating intermolecular interaction energies.

We augment the recently introduced same number of optimized parameters (SNOOP) scheme [K. Kristensen et al., J. Chem. Phys. 142, 114116 (2015)] for calculating interaction energies of molecular dimers with an F12 correction and generalize the method to enable the determination of interaction energies of general molecular clusters. The SNOOP, uncorrected (UC), and counterpoise (CP) schemes with/without an F12 correction are compared for the S22 test set of Jurecka et al. [Phys. Chem. Chem. Phys. 8, 1985 (2006)]-which consists of 22 molecular dimers of biological importance-and for water and methane molecular clusters. The calculations have been performed using the Resolution of the Identity second-order Møller-Plesset perturbation theory method. We conclude from the results that the SNOOP scheme generally yields interaction energies closer to the complete basis set limit value than the UC and CP approaches, regardless of whether the F12 correction is applied or not. Specifically, using the SNOOP scheme with an F12 correction yields the computationally most efficient way of achieving accurate results at low basis set levels. These conclusions hold both for molecular dimers and more general molecular clusters.

Explicitly correlated second-order Møller-Plesset perturbation theory in a Divide-Expand-Consolidate (DEC) context.

We present the DEC-RIMP2-F12 method where we have augmented the Divide Expand-Consolidate resolution-of-the-identity second-order Møller-Plesset perturbation theory method (DEC-RIMP2) [P. Baudin et al., J. Chem. Phys. 144, 054102 (2016)] with an explicitly correlated (F12) correction. The new method is linear-scaling, massively parallel, and it corrects for the basis set incompleteness error in an efficient manner. In addition, we observe that the F12 contribution decreases the domain error of the DEC-RIMP2 correlation energy by roughly an order of magnitude. An important feature of the DEC scheme is the inherent error control defined by a single parameter, and this feature is also retained for the DEC-RIMP2-F12 method. In this paper we present the working equations for the DEC-RIMP2-F12 method and proof of concept numerical results for a set of test molecules.

[Correlation of FOXA1 with the malignancy and progression of prostate cancer].

OBJECTIVE: To study the relationship of the expression of FOXA1 in the prostate cancer (PCa) tissue with the Gleason score and clinical staging of PCa and with castration-resistant PCa (CRPC). METHODS: Using the immunohistochemical method, we detected the expressions of FOXA1 and Ki-67 in the pathological sections of 35 cases of PCa and 21 cases of benign prostatic hyperplasia (BPH). Then we analyzed their correlation with the Gleason score and TNM staging of PCa and that with CRPC. RESULTS: The positive expression of FOXA1 was significantly higher in the PCa than in the BPH tissue (P < 0.001) and was positively correlated with that of Ki-67 (P < 0.001) as well as with the Gleason score (P = 0.027) and clinical staging of PCa (P = 0.002), but showed no correlation with CRPC (P = 0.391). CONCLUSION: The positive expression of FOXA1 is increased in PCa, most significantly in the advanced stage of the tumor.

[Autophagy and prostate cancer].

The role of autophagy is known to be highly complex and context-dependent, and may be characterized as both tumor suppression and tumor promotion in some tumors, such as breast cancer and prostate cancer. This review outlines recent advances in the studies of the involvement of autophagy in the development, progression and treatment of prostate cancer, focusing on autophagy modulation during androgen deprivation, with a special discussion on the regulatory effect of androgens on the autophagy of prostate cancer cells. A critical evaluation and analysis of the studies suggests that autophagy inhibition combined with androgen deprivation therapy is a promising approach to the treatment of prostate cancer.

[LncRNA in prostate cancer: an update].

Recent studies have demonstrated the importance of the non-protein coding part of human genome in carcinogenesis and metastasis of prostate cancer. Long non-coding RNAs (lncRNAs) play a key regulatory role in prostate cancer biology. LncRNAs are dysregulated in prostate cancer and the expression levels of certain lncRNAs are associated with the recurrence, metastasis and prognosis of cancer. It is also proved that lncRNAs, as oncogenes, can promote carcinogenesis and development of prostate cancer. This review focuses on the progress in the studies of lncRNAs in prostate cancer.

[Expressions of SIgA and alpha 1-AR in benign prostatic hyperplasia combined with chronic prostatitis and their implications].

OBJECTIVE: To explore the expressions of SIgA and alpha l-AR in benign prostatic hyperplasia (BPH) complicated by chronic prostatitis (CP) and their implications. METHODS: According to the preoperative findings of expressed prostatic secretion (EPS), transrectal prostate ultrasonography, prostate-specific antigen (PSA), international prostate symptom score (IPSS), clinical symptoms, chronic pelvic pain syndrome (CPPS) and postoperative histopathology, 62 cases of BPH pathologically confirmed after transurethral plasma kinetic resection of the prostate (PKRP) were divided into a BPH group (n = 32) and a BPH + CP group (n = 30). The expressions of SIgA and alpha 1-AR in the prostate tissue were determined by immunohistochemistry and PT-PCR. RESULTS: Of the 62 cases, 30 were found to be BPH + CP, and the other 32 to be BPH. The expressions of SIgA and alpha1-AR were significantly higher in the BPH + CP than in the BPH group (0.380 8 +/- 0.144 3 vs 0.295 4 +/- 0.008 4 and 0.440 5 +/- 0.104 1 vs 0.383 2 +/- 0.013 6, P < 0.05). CONCLUSION: The upregulated expressions of SIgA and alpha1-AR expression in BPH complicated by CP suggest a certain association between CP and BPH, and that inflammation may be a pathogenic factor of BPH and correlate with its pathological development.

[Impact of high altitude and hypoxia on sperm concentration].

Recent studies show that long exposure to high altitude and hypoxia can seriously affect men's reproductive health by reducing their sperm concentration, which decreases with the increase of altitude. High altitude and hypoxia are strongly associated with spermatogenic reduction, sperm DNA damage, sperm apoptosis, and decreased level of sex hormones. This article reviews the mechanisms of high altitude and hypoxia affecting sperm concentration.

Strategies for Optimization of the Clustered Regularly Interspaced Short Palindromic Repeat-Based Genome Editing System for Enhanced Editing Specificity.

The clustered regularly interspaced short palindromic repeats (CRISPR) system is inarguably the most valuable gene editing tool ever discovered. Currently, three classes of CRISPR-based genome editing systems have been developed for gene editing, including CRISPR/CRISPR associate system (Cas) nucleases, base editors, and prime editors. Ever-evolving CRISPR technology plays an important role in medicine; however, the biggest obstacle to its use in clinical practice is the induction of off-target effects (OTEs) during targeted editing. Therefore, continuous improvement and optimization of the CRISPR system for reduction of OTEs is a major focus in the field of CRISPR research. This review aims to provide a comprehensive guide for optimization of the CRISPR-based genome editing system.

[Pentosan polysulfide sodium for chronic non-bacterial prostatitis in the rat model].

OBJECTIVE: To investigate the therapeutic effect of pentosan polysulfide sodium (PPS) on chronic non-bacterial prostatitis (CNP) in rats. METHODS: Based on Robinette's method, we established a CNP model in 80 male SD rats, aged 6 months and weighing 315 - 450 g, by castration followed by subcutaneous injection of estradiol at 0.25 mg / (kg x d) for 30 consecutive days. Then we randomly allocated the model rats into a placebo group (n = 40) and a PPS group (n = 40) to receive intragastric administration of normal saline and PPS, respectively. After 8 weeks of treatment, the pathological changes in the rat prostatic tissue were observed by HE staining. RESULTS: Varied degrees of chronic inflammation and inflammatory cell infiltration were seen in the prostatic tissues of both groups of rats before the treatment. The inflammation was significantly improved after the treatment in the PPS group but not in the placebo group. CONCLUSION: PPS has some therapeutic effect on CNP in the rat, and its mechanism may be associated with the abilities of PPS to repair the damaged glycosaminoglycan layer and inhibit inflammation in the prostate.

[Effects of cyclopamine on the proliferation and cycle of prostate cancer cell line DU145].

OBJECTIVE: To investigate the inhibitory effect of the Hedgehog signal pathway blocker (cyclopamine) on DU145 cells. METHODS: We interfered DU145 cells with cyclopamine at the concentrations of 1, 10, 50 and 100 micromol/L and detected its inhibitory effect on the cells by MTT colorimetry assay at 24, 48 and 72 hours, as well as its effect on the cell cycle by flow cytometry. We also determined the difference in the mRNA expression of cyclin E between the experimental and control groups by RT-PCR at 48 hours after 50 +/- micromol/L cyclopamine intervention. RESULTS: Cyclopamine inhibited the DU145 cells in a time- and dose-dependent manner, with inhibition rates of 7.42, 12.70 and 59.15% in the 10, 50 and 100 micromol/L groups respectively at 24 hours, significantly different from that of the blank control group (P < 0.05). It markedly suppressed the proliferation of the DU145 cells at >10 micromol/L at 24 hours. Flow cytometry showed an obviously increased proportion of stage G1 cells at the concentration of >10 micromol/L after 48-hour intervention, with statistically significant differences from the G1 cell proportions in the control, 10 micromol/L and 50 micromol/ L groups, which were (52.17 +/- 2.21)%, (60.13 +/- 2.75)% and (74.30 +/- 3.52)% respectively (P < 0.01). The apoptotic peak was elevated with the increased concentration of cyclopamine. The cyclin E mRNA expression of the DU145 cells was decreased by 61.90% at 48 hours after 50 micromol/L cyclopamine intervention as compared with the blank control group (P < 0.01). CONCLUSION: Cyclopamine can inhibit the proliferation of DU145 cells, and the mechanism may be related with its effect of down-regulating the cyclin E mRNA expression of DU145 cells and blocking them in stage G1. Cyclopamine can also induce the apoptosis of DU145 cells.

[Expressions of transforming growth factor-beta(1) and Smad4 in rat models of chronic nonbacterial prostatitis and their clinical significance].

OBJECTIVE: To investigate the expressions of transforming growth factor-beta(1) and Smad4 in the prostatic tissue of rat models of chronic nonbacterial prostatitis (CNP), and to explore the mechanisms of CNP and its fibrosis. METHODS: Sixty 6-month-old SD rats were randomly allocated into three groups of equal number: normal control, 30 d CNP model and 45 d CNP model, the models made by castration + high-dose intramuscular injection of estradiol benzoate. The expressions of TGF-beta1 and Smad4 in the prostatic tissue were detected by immunohistochemistry and Western blot. RESULTS: Compared with the normal controls, the 30 d and 45 d CNP rat models showed a significantly increased expression of TGF-beta1 and decreased expression of Smad4 (P < 0.05), even more significantly in the 45 d than in the 30 d group. And the expression of TGF-beta1 was negatively correlated with that of Smad4 in the CNP rat models. CONCLUSION: TGF-beta1 and Smad4 may be involved in the pathogenesis of CNP, and prostatic fibrosis may make the condition difficult to cure.

[Genetic detection and analysis of the VHL gene in patients with sporadic pheochromocytoma].

OBJECTIVE: To carry out a genetic detection and analysis of Von Hippel-Lindau (VHL) gene in Chinese patients with sporadic pheochromocytoma. METHODS: DNA samples were extracted from peripheral blood cells and fresh pheochromocytoma specimens from 41 patients with sporadic pheochromocytoma were assayed by polymerase chain reaction and direct sequencing. The DNA samples of 50 healthy volunteers were extracted from peripheral blood as a control. The PCR products of exon 1, exon 2 and exon 3 were used for molecular analysis of the VHL gene. The genetic detection of family members of VHL gene mutations was also performed. RESULTS: One of mutations was located at nucleotide 572 (G-->C) in exon 2, presenting a codon 120 from arginine (R) to threonine (T). Tow small insertions were locatated at nucleotide 623T (TTTGTtG) in exon 2, leading to a frameshift mutation. There were also three carriers of G572C and three carriers of 623T (TTTGTtG) in family members of the three cases. CONCLUSION: There are some Chinese patients with sporadic pheochromocytoma with tumorigenic VHL gene mutations. It is recommended to use the genetic detection and analysis of VHL gene as a routine examination for patients with sporadic pheoehromoeytoma under the age of 50 years with questionable family history. The genetic detection and analysis of VHL gene may be useful as a marker for the diagnosis of hereditary pheochromocytoma.

[Investigation of sexual dysfunction among chronic prostatitis patients in high altitude area].

OBJECTIVE: To investigate the prevalence and characteristics of sexual dysfunction in patients with chronic prostatitis (CP) in the high altitude area. METHODS: A total of 637 CP patients randomly recruited from different urologic clinics were divided into 4 groups according to their living altitudes. The subjects were scored on the National Institute of the Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF-5), the Chinese Index of Sexual Function for Premature Ejaculation (C-ISFPE) and the questionnaire on ejaculatory difficulties from the University of Washington Symptom Score. RESULTS: In the 637 CP patients, the overall incidences of premature ejaculation (PE), erectile dysfunction (ED) and difficult ejaculation (DE) were 28.4%, 17.6% and 23.9%, respectively, 9.9% with PE, ED and DE simultaneously. With the increase of the living altitude, the scores on IIEF-5 (P = 0.032) and C-ISFPE (P = 0. 047) were obviously decreased, and the incidences of PE (P = 0.047), ED (P = 0.046) and DE (P = 0.019) markedly elevated. Those with PE or ED experienced worse symptoms at a higher altitude (r = 0.249 or 0.267, P < 0.05). The differences were all statistically significant. CONCLUSION: The prevalence and severity of sexual dysfunction are positively correlated with the living altitude among CP patients.

[Mutation screening of VHL gene in a Chinese family with nonsyndromic pheochromocytoma].

OBJECTIVE: To detect the VHL gene mutations in a Chinese family with nonsyndromic pheochromocytoma. METHODS: Mutations of VHL gene were detected in a Chinese family with nonsyndromic pheochromocytoma. Five patients and fifteen relatives were involved in this study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction (PCR). PCR products of all the three exons of VHL gene were purified and a direct gene sequence analysis was performed. RESULTS: All the five patients presented a codon 125 from Histidine (H) to Proline (P) change at nucleotide 587 (A --> C) in exon 2. Seven members of fifteen relatives were carriers with the same VHL gene mutation. Two carriers were detected with bilateral adrenal tumors and right renal cyst respectively by ultrasonic inspection. CONCLUSION: The novel VHL gene mutation detected in this kindred may be the causative gene. Genetic test can detect the carriers in an early period. It is recommended as a routine method of genetic test in nonsyndromic pheochromocytoma patients.

VHL gene mutation analysis of a Chinese family with non- syndromic pheochromocytomas and patients with apparently sporadic pheochromocytoma.

OBJECTIVE: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. MATERIALS AND METHODS: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. RESULTS: Three novel mutations (H125P, 623(?TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ß-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(?TTTGTtG) carriers presented VHL type 2B or type 2C. CONCLUSIONS: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(?TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research into VHLD pathogenesis.