Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID-19. This study is aimed to discover its molecular mechanism and provide potential drug targets. MATERIALS AND METHODS: An LQC target and COVID-19-related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease-gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. RESULTS: A gene set of 65 genes was generated. We then constructed a compound-target network that contained 234 nodes of active compounds and 916 edges of compound-target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta-carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID-19. CONCLUSIONS: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection.

Efficacy of intravesical therapies on the prevention of recurrence and progression of non-muscle-invasive bladder cancer: A systematic review and network meta-analysis.

Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.

Reduced corporal fibrosis to protect erectile function by inhibiting the Rho-kinase/LIM-kinase/cofilin pathway in the aged transgenic rat harboring human tissue kallikrein 1.

Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson's trichrome staining was used to evaluate corporal fibrosis in the corpus cavernosum. We found that the erectile function of rats in the aWTR group was significantly lower than that of other two groups. Masson's trichrome staining revealed that compared with those of the yWTR and aTGR groups, the ratio of smooth muscle cell (SMC)/collagen (C) was significantly lower in the aWTR group. Immunohistochemistry and Western blotting analysis were performed, and results demonstrated that expression of α-SMA was lower, while expressions of transforming growth factor-ß 1 (TGF-ß1), RhoA, ROCK1, p-MYPT1, p-LIMK2, and p-cofilin were higher in the aWTR group compared with those in other two groups. However, LIMK2 and cofilin expressions did not differ among three groups. Taken together, these results indicated that the RhoA/ROCK1/LIMK/cofilin pathway may be involved in the corporal fibrosis caused by advanced age, and hKLK1 may reduce this corporal fibrosis by inhibiting the activation of this pathway to ameliorate age-related ED.

[Thulium laser vaporization versus transurethral resection of the prostate and risk factors for postoperative urethral stricture].

OBJECTIVE: To compare thulium laser vaporization of the prostate (TLVP) and transurethral resection of the prostate (TURP) in the treatment of benign prostate hyperplasia (BPH) analyze the risk factors for postoperative urethral stricture. METHODS: From June 2015 to June 2016, 210 BPH patients in our hospital underwent TURP (n = 126) or TLVP (n = 84). We followed up the patients for 6 months, compared the effects of the two surgical strategies and analyzed the risk factors for postoperative urethral stricture by multivariate logistic regression analysis. RESULTS: Compared with TURP, TLVP achieved significantly shorter time of operation (ï¼»78.6 ± 27.5ï¼½ vs ï¼»53.2 ± 21.6ï¼½ min, P <0.01), postoperative bladder irrigation (ï¼»31.5 ± 2.9ï¼½ vs ï¼»26.1 ± 3.7ï¼½ h, P <0.01), urethral catheterization (ï¼»5.3 ± 1.7ï¼½ vs ï¼»3.7 ± 1.5ï¼½ d, P <0.01) and postoperative hospitalization (ï¼»7.9 ± 2.1ï¼½ vs ï¼»5.5 ± 1.4ï¼½ d, P <0.01) as well as lower urinary leukocyte count at 6 months after surgery (ï¼»32.1 ± 12.6ï¼½ vs ï¼»24.9 ± 11.7ï¼½ /µl, P <0.01) and incidence rate of postoperative complications (11.9% ï¼»15/126ï¼½ vs 3.6% ï¼»3/84ï¼½, P <0.05), particularly that of urethral stricture (7.9% ï¼»10/126ï¼½ vs 1.2% ï¼»1/84ï¼½, P <0.05). Logistic regression analysis showed that the preoperative urinary leukocyte count, postoperative urethral catheterization time, and surgical method were independent risk factors for postoperative urethral stricture. CONCLUSIONS: TLVP, in comparison with TURP, has the advantages of definite effect, fast recovery, high safety and low incidence of postoperative urethral stricture. The main risk factors for postoperative urethral stricture include preoperative urinary tract infection, postoperative urethral catheterization time and surgical method.

[Concentration of basic fibroblast growth factor in plasma and cavernous corpus of aged rat].

OBJECTIVE: To investigate the concentration of basic fibroblast growth factor (bFGF) in aged rat plasma and penile tissues. METHODS: Twelve 24-month-old rats and ten 12-week-old rats were selected. We assessed the erectile responses of rats to cavernous nerve electrostimulation. Then the concentrations of bFGF in the rats' plasma and penile tissues were detected by ELISA kit and smooth muscle contents in the rats' cavernous corpus were evaluated by masson trichrome staining. RESULTS: Compared with the young rats, we found that the erectile function of the aged rats were significantly attenuated (The Max ICP/MAP in the aged rats were 0.41±0.05, 0.44±0.04 and 0.51±0.06 at 2.5 volts, 5.0 volts and 7.5 volts respectively while the Max ICP/MAP in the normal controls were 0.70±0.06, 0.75±0.07 and 0.81±0.04 at 2.5 volts, 5 volts and 7.5 volts respectively, P<0.05). The concentrations of bFGF [The bFGF levels in plasma and penile tissues in the aged rat were (6.43±0.51) µg/L and (598.6±51.7) pg/mg protein respectively while the bFGF levels in the normal control were (10.53±0.42) µg/L and (985.8±76.8) pg/mg protein] were significantly reduced (P<0.05). Furthermore, the smooth muscle contents in the aged rats' penile tissues (0.038±0.005) were dramatically decreased compared with the normal control (0.075±0.006, P<0.05). CONCLUSION: The reduced levels of bFGF may be related to the decreased smooth muscle contents in the penile tissues of the aged rats.

Effect of silencing VDR gene in kidney on renal epithelial calcium transporter proteins and urinary calcium excretion in genetic hypercalciuric stone-forming rats.

OBJECTIVE: To address the molecular mechanisms that the vitamin D receptor (VDR) in the kidney might contribute to decreased renal calcium reabsorption in idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats. METHODS: We silenced the VDR gene in the GHS and normal control (NC) rat kidney in vivo using adenovirus vector-delivered microRNA targeting VDR through renal venous transduction. On days 3-21 after injection with adenovirus, the expression levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters in the kidney were detected. The urine calcium and serum calcium, phosphorus, 1,25(OH)(2)D(3), and parathyroid hormone levels were measured. RESULTS: The basal expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium-sensing receptor were significantly greater in the GHS rats than in the NC rats, and the basal expression levels of transient receptor potential vanilloid receptor subtype 5, transient receptor potential vanilloid receptor subtype 6, calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were significantly lower in the GHS rats than in the NC rats. VDR knockdown in the kidney caused significant increase in renal transient receptor potential vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k) expression levels in the GHS rats. The GHS rats excreted significantly more urine calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone, and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS and NC rats. CONCLUSION: Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further.

[Hypothalamus may be involved in psychogenic erectile dysfunction].

OBJECTIVE: To study the changes of hypothalamus metabolism in patients with psychogenic erectile dysfunction (ED) so as to get some clues to the possible pathogenic factors and pathophysiological mechanism of the problem. METHODS: Six cases of psychogenic ED and 4 normal volunteers were studied by positron emission tomography (PET) for the characteristics of hypothalamus glucose metabolism. Following audiovisual sexual stimulation, the concentration of fluorine-18-fluorodeoxyglucose (18 F-FDG) was determined and the ratio of the left (right) hypothalamus count to the cerebrum count was calculated. RESULTS: Audiovisual sexual stimulation significantly increased 18F-FDG in the volunteers (left: 1.026 +/- 0.115 vs 2.400 +/- 0.210; right: 1.003 +/- 0.187 vs 2.389 +0.196, P < 0.05) as compared with the psychogenic ED patients (left: 2.781 +/- 0.156 vs 2.769 +/- 0.223; right: 2.809 +/- 0.129 vs 2.793 +/- 0.217, P > 0.05). CONCLUSION: Psychogenic ED may not be simply a functional disease; the hypothalamus may be involved in the pathophysiology of the problem.

[A clinical study of prostat combined with an antibiotic for chronic nonbacterial prostatitis].

OBJECTIVE: To evaluate the efficacy and safety of Prostate in combination with an antibiotic for the treatment of chronic nonbacterial prostatitis. METHODS: A double-blind, parallel contrasted, multi-central method was applied in the study. After the Stamey test and expressed prostate secretion (EPS) examination, 160 patients with prostatitis were recruited and randomized into a trial group (80 cases with 1 case missing) and a control group (80 cases). In the trial group, the patients used the levofloxacin and Prostate during the first 4 weeks and Prostate only during the following 4 weeks. In the control group, the patients used the levofloxacin and placebo during the first 4 weeks, and placebo only during the following 4 weeks. Before and 4 and 8 weeks after the treatment, the patients were visited and evaluated by the national institute health-chronic prostatitis symptom index (NIH-CPSI), EPS, and asked about the side. RESULTS: After 4-week and 8-week treatment, the pain index dropped by 3.34 +/- 2.45 and 4.06 +/- 3.03 in the trial group, and effects. 2.28 +/- 2.42 and 3.30 +/- 3.29 in the control; the voiding index dropped by 2.22 +/- 1.79 and 2.77 +/- 2.04 in the trial group, and 1.24 +/- 1.67 and 1.83 +/- 2.25 in the control respectively. There was significant difference between pre-treatment and post-treatment in both the two groups (P < 0.01), while the difference was not significant between 4-week and 8-week post-treatment (P > 0.05). And there was significant difference between the two groups in the pain index and voiding index (P < 0.01), but not in the white blood cell count and lipid in the EPS (P > 0.05). No serious side effects were recorded, and the tolerance to Prostate and placebo showed no significant difference. CONCLUSION: Prostate in combination with an antibiotic can effectively relieve the pain and voiding symptoms and improve the life quality of the patients with nonbacterial prostatitis and well deserves to be recommended in clinical practice.

[The relaxation effects of six extracts from Chinese herbs on the corpus cavernosum tissue of rabbit in vitro].

OBJECTIVE: To study the relaxants effects of six extractions from Chinese Herbs (neferine, tetrandrine, kakonein, scutellarin, ginsenoside Rgl and ginsenoside Rb1) on the corpus cavernosum tissue of rabbit in vitro. METHODS: Isolated stripes of rabbit corpus cavernosum tissue were precontracted with 10(-5) mol/L phenylephrine (PE). Relaxation in response to cumulative doses of six extracts at (10(-8) - 10(-3)) mol/L was determined. RESULTS: On rabbit cavernosal muscle stripes precontracted with PE, neferine, tetrandrine, kakonein and scutellarin showed dose dependent relaxation. IC50 values were 4.60 x 10(-6), 3.73 x 10(-5), 8.03 x 10(-4) and 3.33 x 10(-3) mol/L, respectively. However, in the meantime, it was found that the relaxant effects of ginsenoside Rgl and ginsenoside Rbl less significant to stripes precontracted with PE. When the final concentration was 10(-3) mol/L, the relaxations were only (16.32 +/- 5.45)% and (11.21 +/- 3.10)%. CONCLUSION: Among the six extracts which showed relaxant effects to rabbit cavernosal muscle stripes precontracted with PE, neferine had greater functions than the other five extracts.