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The BF 3 ·Et 2 O-catalysed acetolysis of steroid sapogenins diosgenin, sarsasapogenin and tigogenin in dichloromethane as the solvent instead of acetic anhydride afforded (20S)- and (20R)-22,26-epoxycholestanes (compounds 1 and 2). 22S-23-Acetylsapogenins (compounds 4) were synthesized stereospecifically from 20R-22,26-epoxycholestanes (compounds 2) in good yield. The rearrangement of 22S-23-acetylsapogenins (compounds 4) afforded novel disubstituted dihydropyran furostanol frameworks. Exhaustive NMR characterization of the obtained compounds is provided. Additionally, the structures of the critical compounds (6a and 7a) were unequivocallyconfirmed by single crystal X-ray diffraction studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gelsemium elegans Benth (G. elegans) is highly toxic to humans and rats, but has insecticides and growth promoting effects on pigs and goats. G. elegans is widely used in livestock, but its in vivo dynamics are entirely unknown. Hence, we investigated the toxicokinetic profiles of G. elegans alkaloids after a single oral dose of G. elegans to pigs (1.0 g/kg) and rats (0.1 g/kg). The results indicated that rats were more susceptible to the toxicity of G. elegans than pigs. The toxicokinetic parameters of 22 and 6 components were obtained in pigs and rats, respectively. The components included 9 and 5 gelsedine-type alkaloids in pigs and rats, respectively. The T max results of the 5 gelsedine-type alkaloids indicated that these alkaloids were rapidly absorbed in pigs and rats. The T 1/2 values of the 5 gelsedine-type alkaloids indicated that the elimination rates of these alkaloids in pigs were slower than those in rats. In addition, the C max and AUC results indicated that the degrees of absorption and exposure of most alkaloids in pigs were higher than those in rats except GS-2. However, the C max value of GS-2 (11-methoxy-14-hydroxygelsenicine) in rats was greater than that of pigs, and the C max value of 14-hydroxygelsenicine in pigs was merely greater than 3 times that of rats. The present results suggested that the cause of the toxicological differences species of G. elegans might be related to the degrees of absorption and exposure of gelsedine-type alkaloids, especially for the 14-hydroxygelsenicine and GS-2 in different animals., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. None of the authors have a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the clinical application value of the bladder outlet obstruction index (BOOI) in the diagnosis of BPH., Methods: We retrospectively analyzed the urodynamic parameters and BOOI of 199 cases of BPH diagnosed from July 2016 to September 2018, which were divided into a BOO (n = 119), a suspected BOO (n = 39) and a non-BOO group (n = 41) based on the BOOI. We obtained the prostate volume (PV), IPSS, IPSS-voiding symptom score (IPSS-VS), quality of life score (QOL), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients, compared them among the three groups and analyzed their correlation to BOOI using Pearson's linear correlation analysis., Results: No statistically significant differences were observed in age (P = 0.195), PSA (P = 0.380), IPSS (P = 0.380), IPSS-VS (P = 0.380), QOL (P = 0.380), Qmax (P = 0.380) and PVR (P = 0.912) among the three groups of patients, but PV was remarkably larger in the BOO than in the suspected BOO and non-BOO groups (［58.8 ± 30.0］ vs ［49.8 ± 33.9］ and ［45.5 ± 26.0］ ml, P = 0.031). Pearson's linear correlation analysis showed that BOOI was not correlated significantly to IPSS (r = －0.020, P = 0.778), IPSS-VS (r= －0.013, P = 0.853), QOL (r = －0.107, P = 0.132), Qmax (r = －0.130, P = 0.066) or PVR (r = －0.056, P = 0.433), nor obviously to PV (|r| = 0.178<0.4) though with P = 0.012., Conclusions: BOOI is not significantly correlated to PV, IPSS, IPSS-VS, QOL, Qmax or PVR, and therefore BOO cannot be diagnosed exclusively with BOOI.

Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied. Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores. Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume ( p  < 0.001, p  < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores ( p  > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus ( p  > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus ( p  < 0.01, p  < 0.001). Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.

Our recent study investigated the role of collapsin response mediator protein-2 (CRMP2) on dendritic spine morphology and memory function after traumatic brain injury (TBI). First, we examined the density and morphology of dendritic spines in Thy1-GFP mice on the 1 st day (P1D) and 7th day (P7D) after controlled cortical impact injury (CCI). The dendritic spine density in the hippocampus was decreased on P1D, in which mainly mushroom-type and thin-type spines were lost. The density of dendritic spines was increased on P7D, most of which were of the thin type. Next, we explored the expression of CRMP2 on P1D and P7D. CRMP2 expression was decreased on P1D, but the levels of the CRMP2 breakdown product were increased. On P7D, the expression pattern was the opposite. Then, we constructed CRMP2 overexpression and knockdown plasmids and transfected them into cultured neurons in vitro. CRMP2 increased the dendritic spine density of cultured neurons and the proportion of mushroom-type spines, while CRMP2-shRNA reduced the dendritic spine density and the proportion of mushroom-type spines. To determine the role of CRMP2 in dendritic spines after TBI, we stereotactically injected the CRMP2 overexpression and knockdown viruses into the hippocampus and found that CRMP2 increased the dendritic spine density and the proportion of mushroom-type spines after TBI. Meanwhile, as suggested by the morphological changes, fear conditioning behavioral experiments confirmed that CRMP2 improved memory deficits after TBI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gelsemium elegans (G. elegans) has been used in traditional Chinese medicine. This plant is highly toxic to humans, but can promote the growth of pigs and goats in the veterinary clinic. It is a very complex mixture containing tens or hundreds of different components. Therefore, multiple-component pharmacokinetic studies of G. elegans are a major challenge due to the lack of authentic standards of the components. The purpose of this study was to investigate the plasma pharmacokinetics of multiple components after a single oral dose of G. elegans in goat using a sensitive ultra-performance liquid chromatography coupled to tandem mass spectrometry method for the simultaneous semiquantification of multiple alkaloids without standards. The method was validated in terms of the specificity, LOD, LOQ, linearity, accuracy, precision and matrix effects. To validate the global pharmacokinetic characteristics, the results obtained from the semiquantitative analysis of three authentic compounds (gelsemine, koumine and humantenmine) were compared with the absolute quantification from our recently published method. The results showed that the two methods had similar analytical results, and the obtained values of Tmax, T1/2 and MRT0-t of the three alkaloids were similar between the two methods. In addition, the values of Cmax and AUC0-t of the three alkaloids after normalization were close to the real values, which indicated that this semiquantitative method could be used in the pharmacokinetic study of multiplecomponents. Then the pharmacokinetic parameters of 23 other G. elegans alkaloids in goats were obtained. The results suggested that the gelsedine-type alkaloids were the major active ingredients that predict and explain the efficacy and toxicity of G. elegans., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: To systematically review and meta-analyze the efficacy of moxibustion in treating patients with chronic low back pain (CLBP)., Methods: A systematic search of the Cochrane Library, Web of Science, PubMed, Embase, EBSCO, CBM, Wanfang, CNKI and VIP (until November, 2019) was used to identify studies reporting pain intensity (VAS or NRS), disability (ODI or RMDQ), JOA score, and quality of life (SF-36) in patients with CLBP. Study selection, data extraction was performed critically and independently by two reviewers. Cochrane criteria for risk of bias was used to assess the methodological quality of the trials. The Grading of Recommendations Assessment, Development, and Evaluation Methodology (GRADE) was applied to test the quality of evidence from the quantitative analysis., Results: Ten RCTs, including 987 patients, met the inclusion criteria. Moxibustion had a superior effect on VAS score when compared with western medicine [RR = -1.69, 95%CI(-2.40, -0.98), p < 0.00001] and acupuncture [RR = -0.47, 95%CI(-0.92, -0.02), p=0.04], but it failed to do so when compared with core stability training [RR = -0.41, 95%CI(-0.87, 0.05), p=0.08]. The result showed that moxibustion plus other active treatments (including western medicine, massage, acupuncture and core stability training) had better effects on low back pain relief compared with active treatments alone. Moxibustion showed favourable effects on disability [SMD = -3.80, 95%CI (-5.49, -2.11), p < 0.0001], JOA score [MD = 4.10, 95%CI(2.30, 5.90), p < 0.00001], and SF-36 score [MD = 13.41, 95%CI(9.68, 17.14), p < 0.00001]. The evidence level of the results from the ten studies was determined to be very low to low., Conclusions: It is difficult to draw firm conclusions that moxibustion is an effective intervention for treating CLBP due to the small sample size of eligible trails and the high risk of bias among the available articles. Rigorously designed large-scale RCTs are required to further confirm the results in this review., Competing Interests: Declaration of competing interest No conflict of interests declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The long-term flooding anaerobic environment in paddy soils is conducive to denitrification, which is one of the most important reasons for N 2 O emissions. N 2 O can be transformed to nitrogen gas (N 2 ) by bacteria and archaea containing nitrous oxide reductase (N 2 OR) encoded by the nosZ gene, which is the only known biological pathway of N 2 O consumption in soil. nosZ-I is known to be typical in denitrifying bacteria, which is one of the clades of the nosZ gene and is mainly possessed a Tat signal peptide motif. Although many researchers have studied N 2 O emission characteristics of paddy soil, the capacity of N 2 O consumption and the response mechanism of related functional microorganisms in paddy fields is not yet clear. To verify the effect of exogenous N 2 O on N 2 O consumption and nosZ-I gene, a pot trial experiment was performed under anaerobic conditions. We collected intact soil cores from flooding paddy fields at a 0-5 cm depth, and exogenous N 2 O gas was input through the bottom of flooding paddy soil cores. Meanwhile, a control treatment (CK) with no additional N 2 O gas was also performed. The dynamic characteristics of the added exogenous N 2 O concentration through the intact soil cores, the content of inorganic nitrogen, and DOC were systematically monitored. In addition, the change in the nosZ-I population diversity and community composition were investigated by high-throughput sequencing approaches, with the purpose of revealing the N 2 O uptake ability of flooded paddy soil and the response mechanism of the nosZ-I population. The results showed that 97.39% of exogenous N 2 O diffused into the soil cores, and only 0.72%-7.75% of exogenous N 2 O escaped from the soil surface. The N 2 O released in the headspace of soil cores could continue being absorbed and consumed by the flooding soil column. In addition, 67.10% of the N 2 O escaped to the headspace was consumed in exogenous N 2 O treatment after 192 h of incubation, which was higher than that in CK treatment, and the N 2 O consumption rate increased by 144.2% than that in CK treatment. Meanwhile, the consumption of NH 4 + -N, NO 3 - -N, and DOC consumed during exogenous N 2 O addition treatment was 19.65%, 16.29%, and 8.41% higher than that in CK treatment, respectively. However, the diversity of the nosZ-I gene community had no significant difference; the community composition of nosZ-I -containing bacteria changed significantly after 192 h when exogenous N 2 O was input. The abundances of OTU5004, OTU5065, OTU960, and OTU1282 ( Proteobacteria ) significantly increased, which were the dominant bacterial strain of nosZ-I gene on the OTU level. Compared with the initial sample and CK, the abundance of the OTU5004 strain increased by 7.3% and 4.63%, and the abundance of the OTU5265 strain ( Azoarcus sp.) increased by 0.33% and 0.15%, respectively. The result indicated that the flooding paddy soil column at the soil layer of 0-5 cm has a strong N 2 O absorption and consumption ability. In summary, compared with CK, the addition of exogenous N 2 O significantly accelerated the N 2 O consumption rate, improved the consumption potential of flooding paddy soil column, promoted carbon and nitrogen conversion, and changed nosZ-I community composition. These results would provide a new reference for reducing atmospheric N 2 O emissions.

Background: Hypertrophic scar (HS) is characterized by the increased proliferation and decreased apoptosis of myofibroblasts. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts. Thus, the stimulation of myofibroblast apoptosis is a possible treatment for HS. We aimed to explore that whether over-activated myofibroblasts can be targeted for apoptosis by anticancer drug elesclomol., Methods: 4',6-diamidino-2-phenylindole staining, flow cytometry, western blotting, collagen gel contraction and immunofluorescence assays were applied to demonstrate the proapoptotic effect of elesclomol in scar derived myofibroblasts and TGF-β1 induced myofibroblasts. The therapeutic potential of elesclomol was investigated by establishing rabbit ear hypertrophic scar models., Findings: Both 4',6-diamidino-2-phenylindole staining and flow cytometry indicated that elesclomol targets myofibroblasts in vitro. Collagen gel contraction assay showed that elesclomol inhibited myofibroblast contractility. Flow cytometry and western blot analysis revealed that elesclomol resulted in excessive intracellular levels of reactive oxygen species(ROS), and caspase-3 and cytochrome c proteins. Moreover, compared with the control group, the elesclomol group had a significantly lower scar elevation index in vivo. Immunofluorescence assays for TUNEL and α-smooth muscle actin indicated that elesclomol treatment increased the number of apoptotic myofibroblasts., Interpretation: The above results indicate that elesclomol exerted a significant inhibitory effect on HS formation via targeted myofibroblast apoptosis associated with increased oxidative stress. Thus, elesclomol is a promising candidate drug for the treatment of myofibroblast-related diseases such as HS., Competing Interests: Declaration of Competing Interest The authors declare no competing interests with relevance to this study., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (C max , 30.16 ± 5.85, 5.61 ± 0.73 ng/ml, respectively) at 0.25 hr. Both compounds were completely eliminated from the plasma after 24 hr. After single oral administration, SA and DHSA rapidly increased to reach their C max (3.41 ± 0.36, 2.41 ± 0.24 ng/ml, respectively) at 2.75 ± 0.27 hr. The half-life (T 1/2 ) values were 2.33 ± 0.11 hr and 2.20 ± 0.12 hr for SA and DHSA, respectively. After multiple oral administration, the average steady-state concentrations (C ss ) of SA and DHSA were 3.03 ± 0.39 and 1.42 ± 0.20 ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance., (© 2020 John Wiley & Sons Ltd.)

Aims/introduction: Type 2 diabetes mellitus is a chronic metabolic disorder characterized by islet β-cell dysfunction, which might result from the activation of islet stellate cells (ISCs). Our recent study showed that a specific population of ISCs is prone to be activated in type 2 diabetes mellitus accompanied by reduced secretion of insulin. The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled-5 signaling pathway might play an important role in this process. The present study aimed to explore the effects of Wnt5a on the activation of ISCs isolated from db/db mice., Materials and Methods: ISCs were isolated from db/db mice and matched db/m mice. Immunohistochemistry and western blotting analysis were applied for the determination of Wnt5a expression. Exogenous Wnt5a and lentivirus containing the target gene Wnt5a short hairpin ribonucleic acid were used as a molecular intervention. The experiment of transwell and wound healing was used to evaluate the migration of the isolated ISCs., Results: Our data showed that the expression of Wnt5a and frizzled-5 was decreased in the ISCs isolated from db/db mice compared with db/m mice. Both the exogenous Wnt5a and the overexpression of Wnt5a could inhibit the outgrowth rate of ISCs from islets, and its viability, migration and α smooth muscle actin expression. These changes were associated with the inactivation of the Smad2/3 signaling pathway in a frizzled-5-dependent manner., Conclusions: Our observations revealed a potential role of Wnt5a in preventing ISC activation. The maintenance of quiescent ISCs might be a desirable outcome of therapeutic strategies for diabetes mellitus., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Gelsemium elegans Benth. ( G. elegans ), a traditional Chinese medicine, has great potential as an effective growth promoter in animals, however, the mechanism of its actin remains unclear. Here, we evaluated the protective effects of koumine extract from G. elegans against lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in IPEC-J2 cells through alleviation of inflammation and oxidative stress. MTT and LDH assays revealed that koumine significantly reduced LPS cytotoxicity. Transepithelial electrical resistance (TEER) and cell monolayer permeability assays showed that koumine treatment attenuated the LPS-induced intestinal barrier dysfunction with no particularly different effects in tight junction proteins such as ZO-1, claudin-1, and occludin. LPS-triggered inflammatory response was also suppressed by koumine, as evidenced by the downregulated inflammatory factors, including TNF- α , IL-6, IL-1 β , NO, iNOS, and COX-2, which was closely connected with the inhibition of NF- κ B pathway for the decrease of phosphorylation of I κ B α and NF- κ B and nuclear translocation of p-p65. Amount of reactive oxygen species (ROS) and MDA induced by LPS was also reduced by koumine through activation of Nrf2 pathway, and increased in the levels of Nrf2 and HO-1 degradation of keap-1 to promote anti-oxidants, including superoxide dismutase (SOD) and catalase (CAT). To summarize, koumine-reduced the oxidative stress and inflammatory reaction triggered by LPS through regulation of the Nrf2/NF- κ B signaling pathway and preventing intestinal barrier dysfunction.

N6-methyladenosine (m 6 A) is one of the most abundant messenger RNA (mRNA) modifications in eukaryotes and is involved in various key processes of RNA metabolism. In this issue of Nature, Ries et al (2019) described the fundamental features of m6A modification of mRNAs in regulating the composition of the phase-separated transcriptome on the basis of number and distribution, and provide strong evidence that m6A plays a role in regulating phase separation in cells., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial-mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids., (© 2019 Wiley Periodicals, Inc.)

The multicomponent pharmacokinetic study of herbal medicine is a great challenge due to the low plasma concentrations, large range of concentration scales, lack of authentic standards and uncertain interactions of the components. The aim of this work was to explore the in vivo pharmacokinetics of herbal medicine independently of authentic standards using an integrated analytical strategy. First, ion pairs of multiple components were tuned and selected, and then major parameters were optimized for derivative multiple reaction monitoring (DeMRM) by LC-MS/MS, which was combined with characterization of the chemical profiles of the herbal medicine by LC-QqTOF/MS. Second, different concentrations of herbal extracts were employed instead of authentic standards to construct calibration curves for the semiquantitative determination of multiple components in plasma. Taking Gelsemium elegans as an example, in addition to the fully validated and sufficient methodological results, a total of 27 alkaloid components, major bioactive constituents of Gelsemium elegans, were simultaneously monitored in pig plasma. The concentration-time profiles and pharmacokinetic properties of these 27 components were characterized. The absolute quantification of three components was compared with the results obtained using authentic standards, and the method showed very similar analytical characteristics, such as linearity, precision, accuracy, and the values of the pharmacokinetic parameters T max , Vd, Cl and MRT. This analytical strategy was found to be capable of assessing herbal pharmacokinetics independently of specific authentic compounds for each component. This study was the first attempt to systematically reveal the in vivo pharmacokinetics of Gelsemium elegans. This strategy and methodology will find widespread use in the quantitative pharmacokinetic analysis of multiple components independently of standards for herbal medicine, among other applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The pseudogap, d-wave superconductivity and electron-boson coupling are three intertwined key ingredients in the phase diagram of the cuprates. Sr&#95;{2}IrO&#95;{4} is a 5d-electron counterpart of the cuprates in which both the pseudogap and a d-wave instability have been observed. Here, we report spectroscopic evidence for the presence of the third key player in electron-doped Sr&#95;{2}IrO&#95;{4}: electron-boson coupling. A kink in nodal dispersion is observed with an energy scale of ∼50  meV. The strength of the kink changes with doping, but the energy scale remains the same. These results provide the first noncuprate platform for exploring the relationship between the pseudogap, d-wave instability, and electron-boson coupling in doped Mott insulators.

Objective: To study the improvement of lower urinary tract symptoms and related influencing factors in patients with prostate cancer complicated with lower urinary tract symptoms after drugs endocrine therapy. Methods: The clinical data of 80 patients with prostate cancer with lower urinary tract symptoms and receiving drug endocrine therapy in Guizhou Provincial People's Hospital from March 2015 to June 2019 were analyzed retrospectively. All patients were followed up, and the mode of administration of the endocrine therapy, the time of administration, and the international prostate symptom score (IPSS2) and quality of life score (QOL2) after treatment were recorded. The improvement of IPSS score and quality of life score after endocrine therapy was observed. The correlation between variance and age, the prostate volume, PSA, tumor stage, Gleason score, symptom severity, medication mode, and medication time were analyzed by variance, chi-square test and paired sample t test. Results: The differences of QOL and IPSS before and after therapy were statistically significant ( P< 0.05). Chi-square test found that the effective rate of drug endocrine therapy was not related to age (χ 2 =0.800; P= 0.371), tumor stage (χ 2 =0.094; P= 0.759), PSA (χ 2 =0.651; P= 0.420), prostate volume (χ 2 =0.216; P= 0.642), Gleason score (χ 2 =0.157; P= 0.692), symptom severity (χ 2 =0.457; P= 0.499), medication mode (χ 2 =2.910; P= 0.233), and medication time (χ 2 =4.159; P= 0.385). Analysis of variance found that prostate volume and the severity of symptoms was significantly associated with improvement in lower urinary tract symptoms. Conclusions: Drug endocrine therapy can effectively improve the lower urinary tract symptoms of patients with prostate cancer, and the more severe the symptoms and prostate volumeof the patients, the more obvious the improvement of lower urinary tract symptoms. The age, tumor stage, PSA, Gleason score, time and manner of administration were not significantly correlated with improvement in lower urinary tract symptoms.

Gelsemium elegans is a flowering plant in the Loganiaceae. Because it can promote the growth of pigs and sheep, it is widely used, including in veterinary clinics, but little information is available about its biological effects. Here, we used high-throughput sequencing to characterize the differentially expressed genes (DEGs) in the ileums of pigs between a control group and a group fed Gelsemium elegans for 45 days. We found that Gelsemium elegans affected many inflammatory and immune pathways, including biological processes such as defense responses, inflammation and immune responses. Moreover, this study identified several important genes related to the anti-inflammatory activity of Gelsemium elegans (e.g., CXCL-8, IL1A, and CSF2), which will be beneficial for further study of the pharmacological mechanisms and clinical applications of Gelsemium elegans.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recent studies show that nitric oxide/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase (NO/ADMA/DDAH) pathway may contribute to the development of sleep disorder. The objective of this study was to explore the inhibitory effect of procyanidin B2 from lotus seedpod (LSPC), a naturally occurring catechin compound, on insomnia and the mechanisms involved. The experiments were performed in brain from Sprague-Dawley rat control and insomniac rats treated or not with LSPC (15, 30, and 45 mg/kg, intragastrically) for 7 days. LSPC treatment reduced walking time and forelimb lifting-up frequency, cerebral levels of noradrenaline, glutamic acid, ADMA, sleep latency, and 8-isoprostane; increased sleep duration, cerebral concentrations of 5-hydroxytryptamine, γ-aminobutyric acid, and NO concomitantly with upregulated cerebral expression of DDAH 1, DDAH2, and neuronal NO synthases in insomniac rats. The present results suggest that LSPC may regulate NO/ADMA/DDAH pathway by inhibiting oxidative stress to treat insomnia in rats when sleep evaluation was achieved on the basis of behavioral criteria., (© 2019 Société Française de Pharmacologie et de Thérapeutique.)

Objective: To investigate the expression characteristics of Tim-3 on natural killer (NK) cells of peripheral blood in patients with acute myeloid leukemia (AML) and its clinical significance. Methods: Peripheral blood was obtained from 39 patients with newly diagnosed AML before intervention, with peripheral blood from 28 cases of healthy volunteers collected as normal control. Using CD3, CD56 and Tim-3 as markers, expression levels of Tim-3 on the peripheral blood NK cells were detected by immune fluorescence labeling and flow cytometry. Results: The ratio of the peripheral blood CD3(-)CD56(+) NK cells in newly diagnosed AML patients (5.74±5.31) %decreased significantly, compared with the normal control (12.55±6.33) % ( t =4.596, P <0.001) . Tim-3 expression on the peripheral blood NK cells in newly diagnosed AML patients (42.67±19.08) % decreased significantly, compared with the normal control group (60.99±20.69) % ( t =3.781, P <0.001) . CD3(-)CD56(+)NK cell ratio of peripheral blood in AML patients was significantly correlated with Chromosome karyotype ( t =2.915, P <0.005) . Expression level of Tim-3 on NK cells in the peripheral blood of AML patients had significant correlation with ratio of CR and NCCN high risk group ( P <0.05) . Conclusion: The rate of NK cells in peripheral blood and the expression level of Tim-3 on NK cells in AML patients decreased significantly.The lower expression level of Tim-3 on NK cells correlate with prognosis of AML.

Objective: To explore the therapeutic effect and mechanism of acupoint catgut embedding for chloasma in premenopausal women with liver qi stagnation., Methods: A total of 92 patients of chloasma in premenopausal women with liver qi stagnation were randomized into an observation group and a control group, 46 cases in each one.In the observation group, acupoint catgut embedding was applied at Ganshu (BL 18), Pishu (BL 20), Sanyinjiao (SP 6), also the surrounding acupuncture was performed at facial part, once a week. In the control group, vitamin C (200 mg per time, 3 times a day) and vitamin E (100 mg per time, once a day) were prescribed for oral administration. Both of the two groups were given treatment for 12 weeks. The score of chloasma area and severity index (MASI), the serum levels of follicular stimulating hormone (FSH), leuteinizing hormone (LH) and estradiol (E 2 ) before and after treatment were observed in the two groups, and the clinical effect of the two groups were compared after 3 months of treatment., Results: Finally, 44 cases in the observation group and 43 cases in the control group completed the study. The effective rate in the observation group was 88.6% (39/44), which was higher than 55.8% (24/43) in the control group ( P <0.01). Compared before treatment, the MASI scores after treatment were reduced in the two groups ( P <0.01, P <0.05), the MASI score in follow-up in the observation group was reduced as compared with after treatment ( P <0.01), and the MASI scores after treatment and in follow-up in the observation group were lower than the control group ( P <0.01). Compared before treatment, the levels of FSH and LH in follow-up were reduced ( P <0.01), there was no significant difference between before treatment and in follow-up in the level of E 2 in the observation group ( P >0.05). There was no significant difference between before treatment and in follow-up in the levels of FSH, LH and E 2 in the control group ( P >0.05). In follow-up, the levels of FSH and LH in the observation group were lower than the control group ( P <0.01, P <0.05), there was no significant difference in the level of E 2 between the two groups ( P >0.05)., Conclusion: Acupoint catgut embedding can improve the clinical symptoms of chloasma in premenopausal women with liver qi stagnation, the mechanism may be related to regulate the serum level of sex hormone to reduce high sensitivity of melanocytes to estrogen.

Background and Aims: Soluble E-cadherin (sE-cadherin) has been observed elevated in patients with various diseases, and implicated in the occurrence and development of those diseases. The implications of sE-cadherin in chronic hepatitis C virus (HCV) infection are still unclear. The purpose of this study is to explore the significance of sE-cadherin in chronic hepatitis C infection and the correlation with treatment response., Methods: 87 chronic HCV infected patients and 60 healthy subjects were enrolled in this study. Blood samples from patients receiving the combined treatment of pegylated interferon-a (Peg-IFN-α) with ribavirin (RBV) were collected before treatment, during 4th, 12th therapy weeks, end of the treatment, and 24 weeks post-therapy. Plasma sE-cadherin level was detected by enzyme-linked immunosorbent assay (ELISA) and the relationship between sE-cadherin and antiviral treatment outcome was analyzed., Results: Plasma sE-cadherin concentrations of Chronic HCV infected patients were significantly higher than that of healthy controls. A strong correlation between sE-cadherin level and the HCV viral load, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and also glutamyl transpeptidase (GGT) level was detected. Chronic HCV infected patients achieving rapid virological response (RVR) and sustained virological response (SVR) had lower baseline sE-cadherin concentrations compared with the non-RVR and non-SVR groups respectively. Univariate and multivariate regression analyses suggested that baseline plasma sE-cadherin level was predictive of therapeutic effect in patients with chronic HCV infection., Conclusion: Baseline sE-cadherin level could be considered as an independent predictor of SVR with Peg-IFN-α plus ribavirin therapy in the Chinese Han population chronic HCV infection patients. Effective antiviral therapy might restore sE-cadherin at physiological levels., (Copyright © 2019. Published by Elsevier B.V.)

Hypertrophic scars are pathological scars that result from abnormal responses to trauma, and could cause serious functional and cosmetic disability. To date, no optimal treatment method has been established. A variety of cell types are involved in hypertrophic scar formation after wound healing, but the underlying molecular mechanisms and cellular origins of hypertrophic scars are not fully understood. Macrophages are major effector cells in the immune response after tissue injury that orchestrates the process of wound healing. Depending on the local microenvironment, macrophages undergo marked phenotypic and functional changes at different stages during scar pathogenesis. This review intends to summarize the direct and indirect roles of macrophages during hypertrophic scar formation. The in vivo depletion of macrophages or blocking their signaling reduces scar formation in experimental models, thereby establishing macrophages as positive regulatory cells in the skin scar formation. In the future, a significant amount of attention should be given to molecular and cellular mechanisms that cause the phenotypic switch of wound macrophages, which may provide novel therapeutic targets for hypertrophic scars.

In this study, the swabs were collected among patients with an influenza-like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.

Two new flavonoid glycosides, named viscumneoside XII (1), and viscumneoside XIII (2); a new dihydrogen flavonoid glycoside product named viscumneoside XIV (3), were isolated from the aerial part of Viscum album, along with seven known compounds (4-10). Their structures were identified by analysis of spectroscopic data. In addition, cytotoxicity assay showed that 1, 2 and 3 possessed significant inhibitory activities against C6, A549 and MDA-MB-231 (the inhibition rate arrived about 50%, 70% and 74% respectively with IC 50 ≤ 60.00 μmol·L -1 ), while the inhibition of TF-1 and Hela was not significant., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The present paper describes a novel two-dimensional liquid chromatography (2D-LC) system, which is comprised of a first-dimensional ion exchange chromatography (IEX1) column, trap column, and second-dimensional reversed-phase chromatography (RP2) column system. The biological sample is separated by the first-dimensional LC using an IEX column to remove interferences. The analytes are transferred to the trap column after heart-cutting. Then, the analytes are transferred to the second-dimensional LC using an RP2 column for further separation and ultraviolet detection. This 2D-LC system can offer a large injection volume to provide sufficient sensitivity and exhibits a strong capacity for removing interferences. Here, the determination of three monoterpene indole alkaloids (MIAs; gelsemine, koumine, and humantenmine) from Gelsemium in biological matrices (plasma, tissue, and urine) was used this 2D-LC system. After a rapid and easy sample preparation method based on protein precipitation, the sample was injected into the 2D-LC. The method was developed and validated in terms of the selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The sample preparation time for the three MIAs was 15 min. The LOD for these compounds was 10 ng/mL, which was lower than the developed HPLC methods. The results showed that this method had good quantitation performance and allowed the determination of gelsemine, koumine, and humantenmine in biological matrices. The method is rapid, exhibits high selectivity, has good sensitivity, and is low-cost, thus making it well-suited for application in the pharmaceutical and toxicological analysis of Gelsemium. Graphical abstract.

Aim: To investigate the association of urinary glucose excretion with levels of serum uric acid in adults with newly diagnosed diabetes., Methods: A total of 597 people with newly diagnosed diabetes, confirmed in an oral glucose tolerance test, were included in the present study. The participants were divided into two groups: 142 participants with low urinary glucose excretion and 455 with high urinary glucose excretion. Demographic characteristics and clinical variables were evaluated. The association of urinary glucose excretion with uric acid was analysed using multivariable regression analysis., Results: The low urinary glucose excretion group had a significantly higher prevalence of hyperuricaemia than the high urinary glucose excretion group. Moreover, urinary glucose excretion was negatively associated with uric acid level. The correlation remained significant after adjusting for potential confounders, including gender, age, fasting plasma glucose, 2-h plasma glucose and BMI. The results also showed that participants with high urinary glucose excretion were at decreased risk of hyperuricaemia (odds ratio 0.47, 95% CI 0.27-0.80; P = 0.006)., Conclusion: Urinary glucose excretion was independently associated with uric acid level in participants with newly diagnosed diabetes. In addition to lowering blood glucose, promoting urinary glucose excretion may also be an effective approach to reducing serum uric acid levels, especially for people with diabetes complicated with hyperuricaemia., (© 2019 Diabetes UK.)

A novel optimised isolation method, TLC-bioautography, was evaluated and utilised in this research. Antibacterial compounds which were isolated from the dichloromethane extract of Ferula ferulioides (Steud.) Korovin were detected by means of the method. Their structures were elucidated by extensive spectral and chemical methods. Their antibacterial activities against drug-resistant Staphylococcus aureus ( S. aureus) strains were evaluated with broth microdilution method, and the results proved that TLC-bioautography was an effective and highly efficient way to screen natural compounds from plant extracts against drug-resistant strains.

Diffuse axonal injury (DAI) is accompanied frequently by adverse sequelae and psychiatric disorders, such as anxiety, leading to a decreased quality of life, social isolation, and poor outcomes in patients. The mechanisms regulating psychiatric disorders post-DAI are not well elucidated, however. Previous studies showed that endoplasmic reticulum (ER) stress functions as a pivotal factor in neurodegeneration disease. In this study, we showed that DAI can trigger ER stress and unfolded protein response (UPR) activation in both the acute and chronic periods, leading to cell death and anxiety disorder. Treatment with 4-phenylbutyrate (4-PBA) is able to inhibit the UPR and cell apoptosis and relieve the anxiety disorder in our DAI model. Later (14 days post-DAI) 4-PBA treatment, however, can restore only the related gene expression of ER stress and UPR but not the psychiatric disorder. Therefore, the early (5 min after DAI) administration of 4-PBA might be a therapeutic approach for blocking the ER stress/UPR-induced cell death and anxiety disorder after DAI.

Objective: To investigate the pathological characters of urothelial barrier in prostatic ducts of elderly male SD rats. Methods: Ten elderly male SD rats were anesthetized with chloral hydrate and then took the bladder, prostatic urethra and prostate tissues for serial pathological sections and HE staining. Immunohistochemical method was used to detect the expression of the Cytokeratin 7 (CK7), Cytokeratin 20 (CK20), Uroplakin Ⅲ (UP Ⅲ), Zonula occludens-1 (ZO-1) and Occludin in issues, and to make densitometric analysis ( IA ) on immunohistochemical results of each antibody. Results: HE staining observed that urothelial umbrella cells exist in the bladder, prostatic urethra and proximal prostatic duct. Immunohistochemical method showed the CK7, UPⅢ, ZO-1 and Occludin were positive in bladder, prostatic urethra and prostatic duct, while CK20 was negative. CK7 and UPⅢ were positive in the proximal prostatic duct, and negative in the bottom of the ductal acinar lumen; ZO-1 and Occludin were positive in prostatic duct. The IOD/Area values of CK7 and UP Ⅲ, in bladder, prostatic urethra, proximal prostatic duct, the middle of prostatic duct and bottom of the ductal acinar lumen, were 0.16, 0.13, 0.06, 0.05, 0.00 and 0.17, 0.16, 0.08, 0.05, 0.00( P< 0.05,respectively). The expression of ZO-1 and Occludin in bladder (0.14 and 0.13) were higher than those in other tissues (0.11-0.12 and 0.09-0.10, P< 0.05); the expression of ZO-1 and Occludin, which in proximal prostatic duct to the middle of prostatic duct and bottom of the ductal acinar lumen, had no significant difference (0.12-0.11 and 0.09-0.09, P> 0.05). The IA values of CK20 were extremely low (0.00-0.01, P> 0.05). Conclusion: Urothelial barriers partially exist in the prostatic ducts of elderly male SD rats, and with the prostatic ducts gradually extending to the bottom of acinar lumen, the urothelial barriers disappear. The results lay a foundation for further study on the repair of urinary epithelial barrier after prostatectomy.

This work investigated the cultivation of Chlorella vulgaris in a thin-film flat plate photobioreactor under outdoor conditions and using digested piggery wastewater as the culture medium. The algal cells were able to adapt quickly to the wastewater and outdoor conditions. A specific growth rate of 0.12 day -1 was obtained in the exponential growth phase, which was slightly higher than that during indoor cultivation using artificial culture medium. Results showed that Chlorella vulgaris effectively removed TN, TP, and COD by 72.48%, 86.93%, and 85.94%. Due to the difference in culture conditions and phosphorus availability, the biomass from outdoor cultivation contained higher lipid content and more unsaturated fatty acids compared to indoor cultures, while the amino acid composition was unaffected. Results of metallic element assay indicated that the biomass cultured with wastewater conformed to the standards required for animal feed additive production. The overall cost of the biomass production in the thin-film flat plate photobioreactor (32.94 US$/kg) was estimated to be 4.67 times lower than that of indoor cultivation (154.04 US$/kg). Together, these results provide a basis for large-scale outdoor production of microalgae and wastewater bioremediation.

Objective: This study was performed to determine the antigenic and genetic characteristics and evaluate potential vaccine efficacy of influenza A (H1N1)pdm09 in Yantai from August 2009 to August 2017., Materials and Methods: A total of 10  236 swabs were collected among patients with an influenza-like illness who were admitted to two sentinel surveillance hospitals in Yantai, East China, from August 2009 to August 2017. All specimens were cultured in Madin-Darby canine kidney cells and identified by haemagglutination-inhibition assay. Complete sequences of haemagglutinin (HA) and neuraminidase of 51 influenza A(H1N1)pdm09 strains circulating in Yantai were amplified, sequenced and analysed using molecular and phylogenetic methods. The potential vaccine efficacy was calculated using the p epitope model which measured the antigenic variation based on the changes in the dominant epitope of HA., Results: The results showed that most Yantai strains were grouped into genetic clades 1.7, 6C, 6B.1 and 6B.2. The amino acid substitutions accumulated gradually in HA proteins and considerable genetic variation were observed in circulating A(H1N1)pdm09 viruses during the seven influenza seasons. The V241I, N369K, N386K and K432E mutations which may change the binding pattern and affinity of oseltamivir for neuraminidase were detected in the strains circulating in 2016/2017 and 2017/2018 seasons and the recommended vaccine strains could afford optimal protection against the influenza A/H1N1pdm09., Conclusions: Although influenza A(H1N1)pdm09 viruses acquired significant genetic variation over the course of seven influenza seasons, the recommended vaccine strains still afforded protection against main circulating strains. Continuous epidemiological and virological surveillance are necessary., (© 2018 Wiley Periodicals, Inc.)

Background: Müller cell gliosis not only plays an important physiological role by maintaining retinal neuronal homeostasis but is also associated with multiple pathological events in the retina, including optic nerve crush (ONC) injury. Modulating Müller cell gliosis contributes to the creation of a permissive environment for neuronal survival. However, the underlying mechanism of Müller cell gliosis has remained elusive., Objective: To investigate the underlying mechanism of Müller cell gliosis after ONC., Methods: Rats with ONC injury were transfected with miRNA-21 (miR-21) agomir (overexpressing miR-21) or antagomir (inhibiting miR-21) via intravitreous injection. Immunofluorescence and western blotting were performed to confirm the effects of miR-21 on Müller cell gliosis. The retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography and the positive scotopic threshold response (pSTR) was recorded using electroretinogram., Results: In the acute phase (14 days) after ONC, compared with the crushed group, inhibiting miR-21 promoted Müller cell gliosis, exhibiting thicker processes and increased GFAP expression. In the chronic phase (35 days), inhibiting miR-21 ameliorated Müller cell gliosis, which exhibited thicker and denser processes and increased GFAP expression. Retinal ganglion cell (RGC) counts in retinas showed that the number of surviving RGCs increased significantly in the antagomir group. The thickness of the RNFL increased significantly, and pSTR showed significant preservation of the amplitudes in the antagomir group., Conclusions: Inhibition of miR-21 promotes RGC survival, RNFL thickness and the recovery of RGC function by modulating Müller cell gliosis after ONC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To compare the efficiency and safety of thulium laser resection of the prostate-tangerine technique (TmLRP-TT) and transurethral resection of the prostate (TURP) for the treatment of benign prostatic hyperplasia (BPH) of various sizes. Methods: Clinical data of 249 BPH patients received TmLRP-TT or TURP were retrospectively collected. Patients were divided into small prostate group [prostate volume (PV)<40 ml], medium prostate group (40 ml≤PV<80 ml) and large prostate group (PV ≥ 80 ml) based on transrectal ultrasound (TRUS) results. Age, PV, Prostate-specific antigen (PSA), International prostate symptom score (IPSS), Quality of life (QoL), maximum of flow rate (Q(max)) and post-void residual urine (PVR) of patients received TmLRP-TT or TURP in each group were analyzed, as well as the perioperative data including operation time, hemoglobin and serum sodium level, transfusion, postoperative length of indwelling catheter and postoperative hospital stay. Furthermore, the postoperative complication rates of patients received the two operative methods in each group up to follow-up of 6 months were compared. Results: As for baseline indicators, there were no significant differences regarding age, prostate volume, PSA, IPSS, QoL, Qmax and PVR of patients received TmLRP-TT or TURP in each group (all P> 0.05). In the small prostate group, there were no significant differences with operation time, hemoglobin and serum sodium level, transfusion, postoperative length of indwelling catheter and postoperative hospital stay received TmLRP-TT or TURP (all P> 0.05). For the medium prostate group, patients received TmLRP-TT underwent longer operation time [(67.4±15.1) vs (57.5±11.5) min, P< 0.001], but shorter length of indwelling catheter [(1.5±0.6) vs (3.1±0.9) d, P< 0.001] and postoperative hospital stay [(3.5±0.9) vs (5.6±1.0) d, P< 0.001], and there were no significant differences regarding transfusion rate (3/73 vs 1/78, P= 0.280), hemoglobin [(9.8±9.0) vs (12.2±9.6) g/L, P= 0.107] and serum sodium decrease [(2.07±3.65) vs (2.97±3.35) mmol/L, P= 0.373]. In the large prostate group, patients received TmLRP-TT also underwent longer operation time [(86.5±14.3) vs (76.7±14.6) min, P= 0.022], but less hemoglobin [(11.3±13.8) vs (23.3±15.0) g/L, P= 0.006] and serum sodium decrease [(2.41±2.67) vs (4.00±6.22) mmol/L, P= 0.042], lower transfusion rate (5/27 vs 0/24, P= 0.026), and shorter length of indwelling catheter [(1.8±0.7) vs (4.3±1.5) d, P< 0.001] as well as postoperative hospital stay [(3.7±1.1) vs (6.1±1.7) d, P< 0.001]. Less overall complications were encountered in the medium (38/73 vs 24/78, P= 0.008) and large (26/27 vs 10/24, P< 0.001) prostate group who received TmLRP-TT, which was not seen in the small prostate group ( P= 0.589). Conclusions: TmLRP-TT and TURP are similarly efficient for the treatment of BPH of various sizes. For BPH patients with medium and large prostate, TmLRP-TT demonstrated significant advantages in reducing the overall complications, although the operation time was slightly longer.

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC 50 of 1.22 and 1.33 μmol·L -1 , and the SC 50 of 4.34 and 8.22 μmol·L -1 , respectively., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Climate oscillation may have a profound effect on species distributions, gene flow patterns and population demography. In response to environmental change, those species restricted to montane habitats experienced expansions and contractions along elevation gradients, which can drive differentiation among sky islands., Results: The Shangcheng stout salamander (Pachyhynobius shangchengensis) is a cool stream amphibian restricted to high-elevation areas in the Dabie Mountains, East China. In the present study, we used mtDNA genes (Cyt b and ND2) of 193 individuals and 12 nuclear microsatellite loci genotyped on 370 individuals, representing 6 populations (JTX, KHJ, MW, TTZ, BYM and KJY) across the taxon's distribution area, to investigate their genetic variation and evolutionary history of P. shangchengensis. Most populations showed unusually high levels of genetic diversity. Phylogenetic analyses revealed five monophyletic clades with divergence times ranging from 3.96 to 1.4 Mya. Accordingly, significant genetic differentiation was present between these populations. Bayesian skyline plot analyses provided that all populations underwent long-term population expansions since the last inter-glacial (0.13 Mya ~ 0.12 Mya). Msvar analyses found recent signals of population decline for two northern populations (JTX and KHJ) reflecting a strong bottleneck (approximately 15-fold decrease) during the mid-Holocene (about 6000 years ago). Ecological niche modelling has shown a discontinuity in suitable habitats for P. shangchengensis under different historical climatic conditions., Conclusions: Our results suggest that the niche conservatism of P. shangchengensis and sky island effects may have led to long-term isolation between populations. In sky island refuges, the mid-latitude Dabie Mountains have provided a long-term stable environment for P. shangchengensis, which has led to the accumulation of genetic diversity and has promoted genetic divergence.

Antimicrobial resistance is the greatest threat to the treatment of bacterial infectious diseases. The development of resistance-modifying agents (RMAs) represents a promising strategy to mitigate the spread of bacterial antimicrobial resistance. In this study, a natural product, isovalerylshikonin (IVS), was isolated from Arnebia euchroma, a traditional Chinese medicine herb, that exhibited marginal antibacterial activity against drug-resistant Staphylococcus aureus RN4220, with a minimum inhibitory concentration (MIC) of 16 mg/L. In addition, a synergistic effect between IVS and streptomycin (STM) was detected by the microdilution antimicrobial chequerboard assay, with a reduction in the MIC of STM by up to 16-fold against strain RN4220. A bacterial ethidium bromide efflux assay and reverse transcription PCR were performed to investigate the synergistic mechanism. IVS significantly inhibited bacterial efflux and expression of msrA mRNA in vitro. A murine peritonitis/sepsis model was employed to test the in vivo synergistic activity of IVS and STM. IVS synergistically decreased bacterial counts with STM in peritoneal, spleen and liver tissue and increased mouse survival with STM in 7 days. The acute toxicity of IVS was tested and the 50% lethal dose (LD 50 ) of IVS with a single exposure was 2.584 g/kg in mice. Overall, IVS, a low-toxicity RMA, exhibited synergistic antibacterial activities in vitro and in vivo against drug-resistant S. aureus. The effects were mediated by suppression of msrA mRNA expression and reduced bacterial efflux. In addition, these data support that IVS is a potential RMA against microbial resistance caused by the MsrA efflux pump., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rationale: N-Methylcanadine and N-methylstylopine are two types of isoquinoline alkaloids which are considered to be the main medicinally active constituents of the genus Papaveraceae. However, to date, no metabolism studies of N-methylcanadine and N-methylstylopine have been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of these two alkaloids in rat liver S9., Methods: N-Methylcanadine or N-methylstylopine was incubated with rat liver S9 for 1 h, and then the incubation mixture was processed with 15% trichloroacetic acid. High-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) as a reliable analytical method was used. The structural characterization of these metabolites was performed by the combination of the accurate MS/MS spectra and the known elemental composition., Results: As a result, a total of four metabolites of N-methylcanadine and five metabolites of N-methylstylopine in rat liver S9 were tentatively identified. The cleavage of the methylenedioxy group of the drugs was the main metabolic pathway of N-methylcanadine and N-methylstylopine., Conclusions: The present study is the first in vitro metabolic investigation of N-methylcanadine and N-methylstylopine in rat liver S9 using a reliable HPLC/QqTOF-MS method. The metabolic pathways of N-methylcanadine and N-methylstylopine are tentatively proposed. This work lays the foundation for the in vivo metabolism of the two compounds in animals., (© 2018 John Wiley & Sons, Ltd.)

Timosaponin A3, a saponin in Zhimu, elicited hepatotoxicity via oxidative stress. However, the clinical medication of Zhimu has been historically regarded as safe, probably associated with the antioxidants it contains. However, the related information on the in vivo levels of timosaponin A3 and antioxidants remained unclear on Zhimu treatments. Therefore, a combination of the in vitro metabolism, including microbiota-mediated and liver-mediated metabolism, and in vivo pharmacokinetics and hepatic disposition, was conducted for three xanthones (neomangiferin, mangiferin, and norathyriol) and three saponins (timosaponin B2, timosaponin B3, and timosaponin A3) on Zhimu treatments. Consequently, following oral administration of Zhimu decoction to rats, those saponins and xanthones were all observed in the plasma with severe liver first-pass effect, where mangiferin was of the maximum exposure. Despite the ignorable content in the herb, timosaponin A3 elicited sizable hepatic exposure as the microbiota-mediated metabolite of saponins in Zhimu. The similar phenomenon also occurred to norathyriol, the microbiota-mediated metabolite of xanthones. However, the major prototypes in Zhimu were of limited hepatic exposure. We deduced the hepatic collection of norathyriol, maximum circulating levels of mangiferin, and timosaponin B2 and mangiferin interaction may directly or indirectly contribute to the whole anti-oxidation of Zhimu, and then resisted the timosaponin A3-induced hepatotoxicity. Thus, our study exploratively interpreted the discrepancy between herbal safety and timosaponin A3-induced hepatotoxicity. However, given the considerable levels and slow eliminated rate of timosaponin A3 in the liver, more attention should be paid to the safety on the continuous clinical medication of Zhimu in the future.

Several studies have demonstrated that renal glucose reabsorption is increased in patients with type 2 diabetes. However, the increased renal glucose reabsorption may contribute to the progression of hyperglycemia. Therefore, promoting urine glucose excretion (UGE) by suppression of renal glucose reabsorption is an attractive approach for the treatment of diabetes. Insulin resistance is identified as a major characteristic in the pathogenesis of type 2 diabetes. Thus, our aim was to evaluate the association of UGE with serum insulin levels and insulin resistance in subjects with glucose abnormalities, including prediabetes and newly diagnosed diabetes (NDD). The present study included 1129 subjects, 826 individuals with prediabetes and 303 individuals with NDD. Urine samples were collected within 2 h of oral glucose loading for the measurement of glucose. Fasting serum insulin was measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was assessed. Multiple linear regression analysis and multivariate logistic regression analysis were performed to determine the association of UGE with insulin levels and HOMA-IR. A negative association between serum insulin levels and UGE was observed. The relationship remained significant after adjustment for potential confounders, including age, gender, blood pressure and glucose (β = -5.271, 95% CI: -9.775 to -0.767, p = 0.022). Furthermore, multivariable logistic regression model showed that increased insulin levels were associated with a decreased risk for high UGE after multivariable adjustment. In addition, similar correlation was also observed between HOMA-IR and UGE. HOMA-IR was negatively correlated with UGE after controlling for potential confounders. Moreover, an independent inverse relationship between HOMA-IR and the risk of high UGE was found (OR = 0.85, 95% CI: 0.78-0.93, p < 0.001). In conclusion, insulin levels and HOMA-IR were negatively correlated with UGE after adjusting for potential confounders. Subjects with increased insulin levels or IR were at a decreased risk of high UGE independent of blood glucose. The study suggests that insulin might affect UGE through other ways, in addition to the direct blood glucose-lowering effect, thereby resulting in reduced UGE.

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.

N-acetylgalactosaminyltransferase 2-Angiopoietin-like protein 3-lipoprotein lipase (GALNT2-ANGPTL3-LPL) pathway may be a useful pharmacologic objective for dyslipidemia. The present study was conducted to test the effect of paeoniflorin, a monoterpene Glycoside, on dyslipidemia in mice. Fifty mice were randomly divided into five groups (n = 10): three groups of apolipoprotein E-null (ApoE -/- ) mice treated with paeoniflorin (10 or 20 or 30 mg/kg/day), untreated ApoE -/- mice group, and C57BL/6J control group. Six weeks after treatment, expression of hepatic ANGPTL3, hepatic GALNT2 and adipose tissue LPL, lipid levels in the liver and blood were quantified. Treatment with paeoniflorin (10 or 20 or 30 mg/kg) obviously down-regulated expression of ANGPTL3 and up-regulated expressions of GALNT2 and LPL concomitantly with elevated plasma high-density lipoprotein cholesterol level, reduced plasma concentrations of low-density lipoprotein cholesterol, total cholesterol, triglyceride, malonaldehyde, and 8-isoprostane. The present results suggest that paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An endophytic strain (designated as strain SYPF 8335 T ) was isolated from a root of Panax notoginseng in Wenshan district, Yunnan province of China. Strain SYPF 8335 T grew very slowly and formed white colonies. Phylogenetic analysis of four loci indicated that strain SYPF 8335 T was placed in the Drechmeria clade with Drechmeria campanulata as its closest phylogenetic neighbour. The nucleotide differences between strain SYPF 8335 T and D. campanulata are 30 substitutions in the internal transcriber region region. A key morphological feature that differentiates the two fungi is that D. campanulata produces campanulate conidia. Combined with the morphology and molecular analyses, a new species named Drechmeria panacis sp. nov., is proposed.

Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery. Further, the anti-inflammatory cytokine, interleukin-10, can inhibit nerve scar formation. Saikosaponin a (SSa) is a monomer molecule extracted from the Chinese medicine, Bupleurum. SSa can exert anti-inflammatory effects in spinal cord injury and traumatic brain injury. However, it has not been shown whether SSa can play a role in peripheral nerve injury. In this study, rats were randomly assigned to three groups. In the sham group, the left sciatic nerve was directly sutured after exposure. In the sciatic nerve injury (SNI) + SSa and SNI groups, the left sciatic nerve was sutured and continuously injected daily with SSa (10 mg/kg) or an equivalent volume of saline for 7 days. Enzyme linked immunosorbent assay results demonstrated that at 7 days after injury, interleukin-10 level was considerably higher in the SNI + SSa group than in the SNI group. Masson staining and western blot assay demonstrated that at 8 weeks after injury, type I and III collagen content was lower and nerve scar formation was visibly less in the SNI + SSa group compared with the SNI group. Simultaneously, sciatic functional index and nerve conduction velocity were improved in the SNI + SSa group compared with the SNI group. These results confirm that SSa can increase the expression of the anti-inflammatory factor, interleukin-10, and reduce nerve scar formation to promote functional recovery of injured sciatic nerve., Competing Interests: The authors declare that there are no conflicts of interest associated with this manuscript

Previous investigations have shown molecular cross-talk among activated adenosine monophosphate-activated protein kinase (AMPK), proprotein convertase subtilisin/kexin type 9 (PCSK9), sterol regulatory element-binding proteins (SREBPs), and low-density lipoprotein receptor (LDLR) and that it may be an innovative pharmacologic objective for treating obesity. We scrutinized the beneficial effect of naringin, a flavanone-7- O-glycoside, on obesity and the mechanisms in the present study. We arbitrarily divided 50 mice into five groups ( n = 10): 25 or 50 or 100 mg/kg/day naringin-treated obese mice (gavage for 8 weeks), untreated obese mice, and C57BL/6J control. After 8 weeks, body weight was 51.8 ± 4.4 in the untreated obese mice group, while the weights were 41.4 ± 4.1, 34.6 ± 2.2, and 28.0 ± 2.3 in 25, 50,100 mg/kg naringin groups, respectively. Moreover, naringin treatment significantly decreased plasma 8-isoprostane (an indicator of the oxidative stress) level, fat weight, liver weight, hepatic total cholesterol concentration, hepatic triglyceride concentration, plasma leptin level, plasma insulin content, plasma low-density lipoprotein cholesterol level, and plasma PCSK9 production concomitantly with down-regulated expression of SREBP-2, PCSK9, and SREBP-1, and up-regulated expression of p-AMPKα and LDLR. The present results suggest that naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to reduce the body weight of obese C57BL/6J mice.