Therapeutic effects of ciprofloxacin/bushenhuazhuo combination on chronic prostatitis

Purpose: To evaluate the clinical effect of bushenhuazhuo (a Chinese traditional medicine) in combination with ciprofloxacin (an orthodox medicine) in chronic prostatitis (CP) therapy.Methods: A total of 160 patients who suffered from CP and received treatment in the People’s Hospital of Zhengzhou between April 2012 and June 2014 were selected and divided randomly into treatment and control groups, with 80 patients in each group. Control group was given 0.25 g ciprofloxacin hydrochloride tablets twice a day for 4 weeks. In addition to ciprofloxacin administration, patients in the treatment group also received a dose of bushenhuazhuo preparation twice daily for 4 weeks. Clinical outcomes, quality of life as well as lecithin body and white blood cell (WBC) count in expressed prostatic secretions (EPS-WBC) were evaluated.Results: Cure rates in the treatment and control groups were 90 and 72.50 %, respectively; this difference was significant (p < 0.05). Scores for National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), WBC, and lecithin bodies in the treatment group (8.20 ± 2.20 points, 4.50 ± 1.20 points, and 28.10 ± 2.10 points, respectively) were higher (p < 0.05) than for the control group (12.20 ± 2.20, 6.30 ± 2.20, and 23.30 ± 2.90 points, respectively). The levels of interferon (IFN)-γ and tumour necrosis factor (TNF)-α in the treatment group (26.20 ± 3.30 and 33.80 ± 5.40 mg/L, respectively) were lower than those in the control group (37.70 ± 3.90 and 48.40 ± 3.70 mg/L, respectively), whereas the level of interleukin (IL)-10 in the treatment group (292.60 ± 23.70 mg/L) was higher (p < 0.05) than that in control group (235.80 ± 25.90 mg/L).Conclusion: Ciprofloxacin combined with the Chinese traditional medicine, bushenhuazhuo preparation, demonstrates a marked therapeutic effect in CP. Its mechanism of action may be related to decreased levels of IFN-γ and TNF-α and increased IL-10.Keywords: Bushenhuazhuo, Interferon – γ, Ciprofloxacin, Chronic prostatitis symptom inde

丹蛭降糖胶囊对糖尿病大鼠肾组织NF-κB表达的影响*

Objective: To investigate the expression level of NF- κ B in renal tissue of diabetic rodent model and the regulating action of Danzhi Jiangtang Capsule (DJC) . Methods: 55 male SD rats were randomly divided into 2 groups, normal control group and experimental group. Normal control group was fed with basal diet, the experimental group were fed with high calorie diet. A single intraperitoneal injection of streptozotocin (STZ) of 35mg/kg to establish the animal model of diabetes mellitus, blood glucose was measured after 120h,when the diabetic rodent model was built, the experimental group were randomly divided into 4 groups, high does group of DJC, low does group of DJC , pioglitazone group and model group. In addition to the model group and control group, each group was kept with continuous intragastric administration of drugs for 8 weeks, high does group of DJC, low does group of DJC were treated with 1.08g/ (kg • d), 0.54 g/ (kg • d) by gavage, pioglitazone group was treated with 10mg/ (kg • d) by gavage, the blank group and the model group  were treated with physiological saline 5ml/ (kg • d)  by gavage. Then determined NF-κB by immunohistochemical method and detected blood glucose of rats . Results:  The expression of NF-κB in model group was strongly and significantly increased compared with the normal control group （P＜0.05 or P＜0.01）; after being given Danzhi Jiangtang Capsule for 8 weeks , high expression of NF-κB in high DJC group and low DJC group were significantly decreased (P＜0.05), much more than pioglitazone group . When the diabetic rodent model was built, the blood glucose of model group was increased significantly compared with the control group (P＜0.01).After the experimental group been given Danzhi Jiangtang Capsule for 2 weeks , the level of glucose was decreased significantly compared with model group (P＜0.01) , the blood glucose index declined steadily after 4~8 weeks（P＜0.01）. Conclusion: Danzhi Jiangtang Capsule can reduce blood sugar ,which delay the progression of diabetic nephropathy through inhibiting the high expression of NF- κ B in diabetic rats.目的  探讨NF-κB在糖尿病大鼠肾组织中的表达水平及丹蛭降糖胶囊（DJC）的调节作用。方法  取55只健康雄性大鼠随机分为两组，即正常对照组和实验组。正常对照组予普通饲料喂养，实验组予高脂饲料喂养。采用链尿佐菌素（STZ）单次腹腔注射35mg/kg，建立糖尿病动物模型，120h后测血糖，造模成功后，再将实验组随机分为丹蛭高、低剂量组,吡咯列酮组，模型组。除模型组和对照组外，各组连续灌胃药物8周，丹蛭高、低剂量组分别按1.08g/(kg•d)、0.54 g/(kg•d)灌胃，吡格列酮组按10mg/(kg•d)灌胃，正常对照组和模型组按5ml/(kg•d)给予生理盐水灌胃。免疫组化法检测NF-κB在肾脏中的表达水平，并测定各组大鼠血糖。结果 模型组的NF-κB的表达明显升高，多为强阳性，与正常对照组比较差异有显著性（P＜0.01）；丹蛭高、低剂量组灌胃8周后，两组NF-κB的高表达明显下降，多为弱阳性或不表达，与模型组比较有统计学意义（P＜0.01），疗效优于吡格列酮组。造模后，模型组血糖显著升高（P＜0.01），丹蛭降糖胶囊灌胃2周后，血糖显著下降，与模型组比较（P＜0.01），4~8周后血糖指标下降平稳（P＜0.01）。结论  丹蛭降糖胶囊可能通过抑制糖尿病大鼠NF-κB的高表达，降低血糖，延缓糖尿病肾病的进程

Effect of Fe3+ on the nutrient removal performance and microbial community in a biofilm system

In this study, the influence of Fe3+ on N removal, microbial assembly, and species interactions in a biofilm system was determined. The results showed that maximum efficiencies of ammonia nitrogen (NH4+-N), total nitrogen (TN), phosphorus (P), and chemical oxygen demand (COD) removal were achieved using 10 mg/L Fe3+, reaching values of 100, 78.85, 100, and 95.8%, respectively, whereas at concentrations of 15 and 30 mg/L Fe3+ suppressed the removal of NH4+-N, TN, and COD. In terms of absolute abundance, the expression of bacterial amoA, narG, nirK, and napA was maximal in the presence of 10 mg/L Fe3+ (9.18 × 105, 8.58 × 108, 1.09 × 108, and 1.07 × 109 copies/g dry weight, respectively). Irrespective of Fe3+ concentrations, the P removal efficiency remained at almost 100%. Candidatus_Competibacter (10.26–23.32%) was identified as the most abundant bacterial genus within the system. Determinism (50%) and stochasticity (50%) contributed equally to microbial community assembly. Co-occurrence network analysis revealed that in the presence of Fe3+, 60.94% of OTUs in the biofilm system exhibited positive interactions, whereas 39.06% exhibited negative interactions. Within the OTU-based co-occurrence network, fourteen species were identified as key microbes. The stability of the system was found to be predominantly shaped by microbial cooperation, complemented by competition for resources or niche incompatibility. The results of this study suggested that during chemical P removal in wastewater treatment plants using biofilm methods, the concentration of supplemental Fe3+ should be maintained at 10 mg/L, which would not only contribute to P elimination, but also enhance N and COD removal

Prediction of bone metastasis in non-small cell lung cancer based on machine learning

ObjectiveThe purpose of this paper was to develop a machine learning algorithm with good performance in predicting bone metastasis (BM) in non-small cell lung cancer (NSCLC) and establish a simple web predictor based on the algorithm.MethodsPatients who diagnosed with NSCLC between 2010 and 2018 in the Surveillance, Epidemiology and End Results (SEER) database were involved. To increase the extensibility of the research, data of patients who first diagnosed with NSCLC at the First Affiliated Hospital of Nanchang University between January 2007 and December 2016 were also included in this study. Independent risk factors for BM in NSCLC were screened by univariate and multivariate logistic regression. At this basis, we chose six commonly machine learning algorithms to build predictive models, including Logistic Regression (LR), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), Naive Bayes classifiers (NBC) and eXtreme gradient boosting (XGB). Then, the best model was identified to build the web-predictor for predicting BM of NSCLC patients. Finally, area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity were used to evaluate the performance of these models.ResultsA total of 50581 NSCLC patients were included in this study, and 5087(10.06%) of them developed BM. The sex, grade, laterality, histology, T stage, N stage, and chemotherapy were independent risk factors for NSCLC. Of these six models, the machine learning model built by the XGB algorithm performed best in both internal and external data setting validation, with AUC scores of 0.808 and 0.841, respectively. Then, the XGB algorithm was used to build a web predictor of BM from NSCLC.ConclusionThis study developed a web predictor based XGB algorithm for predicting the risk of BM in NSCLC patients, which may assist doctors for clinical decision makin

Para-Toluenesulfonamide Induces Anti-tumor Activity Through Akt-Dependent and -Independent mTOR/p70S6K Pathway: Roles of Lipid Raft and Cholesterol Contents

Castration-resistant prostate cancer (CRPC) cells can resist many cellular stresses to ensure survival. There is an unmet medical need to fight against the multiple adaptive mechanisms in cells to achieve optimal treatment in patients. Para-toluenesulfonamide (PTS) is a small molecule that inhibited cell proliferation of PC-3 and DU-145, two CRPC cell lines, through p21- and p27-independent G1 arrest of cell cycle in which cyclin D1 was down-regulated and Rb phosphorylation was inhibited. PTS also induced a significant loss of mitochondrial membrane potential that was attributed to up-regulation of both Bak and PUMA, two pro-apoptotic Bcl-2 family members, leading to apoptosis. PTS inhibited the phosphorylation of m-TOR, 4E-BP1, and p70S6K in both cell lines. Overexpression of constitutively active Akt rescued the inhibition of mTOR/p70S6K signaling in PC-3 cells indicating an Akt-dependent pathway. In contrast, Akt-independent effect was observed in DU-145 cells. Lipid rafts serve as functional platforms for multiple cellular signaling and trafficking processes. Both cell lines expressed raft-associated Akt, mTOR, and p70S6K. PTS induced decreases of expressions in both raft-associated total and phosphorylated forms of these kinases. PTS-induced inhibitory effects were rescued by supplement of cholesterol, an essential constituent in lipid raft, indicating a key role of cholesterol contents. Moreover, the tumor xenograft model showed that PTS inhibited tumor growth with a T/C (treatment/control) of 0.44 and a 56% inhibition of growth rate indicating the in vivo efficacy. In conclusion, the data suggest that PTS is an effective anti-tumor agent with in vitro and in vivo efficacies through inhibition of both Akt-dependent and -independent mTOR/p70S6K pathways. Moreover, disturbance of lipid raft and cholesterol contents may at least partly explain PTS-mediated anti-tumor mechanism

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Purpose: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010). Experimental Design: We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control. Conclusions: Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-na\uefve serum APE1 level, which correlated with its tissue level inversely associated with progressionfree survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival

Biology and Behavior of Spathius agrili, a Parasitoid of the Emerald Ash Borer, Agrilus planipennis, in China

Spathius agrili Yang (Hymenoptera: Braconidae) is a gregarious larval ectoparasitoid of the emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) and is a recently described species. Both pest and parasitoid are native to China. In Tianjin City, China, S. agrili typically exhibited 3–4 generations per year, overwintering as a prepupa in a cocoon inside the host gallery. The multiple generations of S. agrili overlapped with its host, as did the emergence dates of the overwintering generation. From a single host, 1–18 S. agrili successfully developed to the adult stage (average 8.4), but in all cases the host was killed. The sex ratio (female: male) of the parasitoid adults emerging from field-collected cocoons was 2:1, whereas the sex ratio of parasitoids reared from field collected eggs and larvae was greater than 3:1. On average, adult females lived 29.1 d, and males lived 23.6 d when fed with 20% honey solution, significantly longer than without a nutritional supplement. Sexual reproduction is the normal mode of reproduction, but in the laboratory females did reproduce parthenogenetically, producing only males. The average fecundity was 23.3 eggs per female in the laboratory. S. agrili developed through five larval instars, and the larvae fed gregariously on the host hemolymph. The generation time from egg to adult wasp was 27–28 d at 22–26°C. Natural parasitism rates were as high as 60%, and in October they reached over 90% in some stands. This study showed that S. agrili is a promising agent for biocontrol of A. planipennis

Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPAR γ

Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control. Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes. Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism. CDK5-mediated phosphorylation at serine 273 (S273) is a unique regulatory mechanism reserved for PPARγ, and this event is linked to insulin resistance in type 2 diabetes mellitus. Our data demonstrates that chiglitazar modulates gene expression differently from two TZDs, rosiglitazone and pioglitazone, via its configuration-restricted binding and phosphorylation inhibition of PPARγ. Chiglitazar induced significantly greater expression of ANGPTL4 and PDK4 than rosiglitazone and pioglitazone in different cell models. These increased expressions were dependent on the phosphorylation status of PPARγ at S273. Furthermore, ChIP and AlphaScreen assays showed that phosphorylation at S273 inhibited promoter binding and cofactor recruitment by PPARγ. Based on these results, activities from pan agonist chiglitazar can be an effective part of a long-term therapeutic strategy for treating type 2 diabetes in a more balanced action among its targeted organs

Revealing histological and morphological features of female reproductive system in tree shrew (Tupaia belangeri)

The tree shrew has been used as a primate animal model in neuroscience studies but it has only rarely been employed in the study of reproductive systems. This is mainly because we know very little about the histological features of reproductive organs of the tree shrew. In this study, we have systematically analyzed the histology of reproductive organs of tree shrew, in comparison with human organs. The uterus of female tree shrew is uterus biomes unicolis, which is connected with an enveloped ovary through a thin fallopian tube. Histologically, the fallopian tube consists of folded mucosa, muscularis and serosa. Like other mammalian animals, the different developmental stages (primordial, primary, secondary and Graafian follicles) of ovarian follicles including inner oocyte and outer granulosa cells are embedded in the cortex. The luminal endometrium, middle muscular myometrium and serosa constitute the wall of uterus of tree shrew. The uterine endometrium contains simple columnar ciliated cells and goblet cells, and there are rich uterine glands in underlying stroma. Furthermore, these glands of tree shrew are round and smaller during anestrus, and become much longer when they are in estrus. The uterine endometrium in younger animals was less developed when compared to a mature tree shrew. Compared to human uterine endometrium, the histological features of tree shrew are very similar, indicating that it could potentially be good primate animal model for studying the diseases in reproductive system

Insights into methionine S-methylation in diverse organisms

Dimethylsulfoniopropionate (DMSP) is an important marine anti-stress compound, with key roles in global nutrient cycling, chemotaxis and, potentially, climate regulation. Recently, diverse marine Actinobacteria, α- and γ-proteobacteria were shown to initiate DMSP synthesis via the methionine (Met) S-methyltransferase enzyme (MmtN), generating S-methyl-Met (SMM). Here we characterize a roseobacterial MmtN, providing structural and mechanistic insights into this DMSP synthesis enzyme. We propose that MmtN uses the proximity and desolvation mechanism for Met S-methylation with two adjacent MmtN monomers comprising the Met binding site. We also identify diverse functional MmtN enzymes in potentially symbiotic archaeal Candidatus Woesearchaeota and Candidate Phyla Radiation (CPR) bacteria, and the animalcule Adineta steineri, not anticipated to produce SMM and/or DMSP. These diverse MmtN enzymes, alongside the larger plant MMT enzyme with an N-terminus homologous to MmtN, likely utilize the same proximity and desolvation mechanism. This study provides important insights into the catalytic mechanism of SMM and/or DMSP production, and proposes roles for these compounds in secondary metabolite production, and SMM cycling in diverse organisms and environments