This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

To evaluate the efficacy and safety of Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. PubMed, VIP, CNKI, Wanfang and other databases were retrieved from the establishment of the database to February 2020 for clinical randomized controlled trial(RCT) about Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. The literatures were screened out according to the inclusion criteria, and RevMan 5.3 software was used for Meta-analysis. A total of 3 100 patients in 27 RCTs were enrolled. According to Meta-analysis, Songling Xuemaikang Capsules combined with conventional Western medicine could effectively reduce systolic blood pressure(MD=-7.88,95%CI[-9.68,-6.08],P<0.000 01) and diastolic blood pressure(MD=-7.85, 95%CI[-9.07,-6.62], P<0.000 01), triglyceride(MD=-0.46, 95%CI[-0.66,-0.26], P<0.000 01) and total cholesterol(MD=-0.92, 95%CI[-1.49,-0.35], P=0.001), but increase HDL cholesterol(MD=0.51, 95%CI[0.28, 0.73], P<0.000 01), with a better effect than the Western medicine group alone. The results of LDL-C analysis showed that there was no significant difference between the two groups(MD=-0.91, 95%CI[-1.82, 0.01], P=0.05). The subgroup analysis suggested that reduced systolic blood pressure may be related to the use of ARB. There was a close correlation between CCB drugs and the decrease of diastolic blood pressure. In addition, there was no significant difference in the compliance and the incidence of adverse reactions. Clinical application of Songling Xuemaikang Capsules combined with Western medicine in the treatment of patients with essential hypertension has clear efficacy and certain safety. More clinical randomized controlled trials are needed for verification in the future.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Capsules ; Drugs, Chinese Herbal ; Essential Hypertension/drug therapy* ; Humans

To systematically evaluate the efficacy and safety of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms. PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, and China biomedical database(CBD) were searched to screen out from the establishment of the database to April 2020 about the clinical randomized controlled trials of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and accompanying symptoms. The articles were selected according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. TSA 0.9.5.10 Beta software was used for sequential analysis, and GRADE 3.6 was used for evidence quality evaluation. A total of 4 532 patients were included in 34 randomized controlled trials. Meta-analysis results showed that: Yangxue Qingnao Granules combined with conventional anti-hypertensive agents reduced systolic blood pressure(MD=-10.56, 95%CI[-13.63,-7.50], P<0.000 01) and diastolic blood pressure(MD=-8.21, 95%CI[-10.84,-5.59], P<0.000 01), improved total effective rate(RR=1.21, 95%CI[1.14, 1.29], P<0.000 01), improved patients dizziness(RR=1.29, 95%CI[1.21, 1.37], P<0.000 01), insomnia(RR=1.66, 95%CI[1.44, 1.91], P<0.000 01), headache(RR=1.32, 95%CI[1.21, 1.43], P<0.000 01), chest distress(RR=1.26, 95%CI[1.12, 1.42], P=0.000 1), memory loss(RR=1.24, 95%CI[1.10, 1.40], P=0.000 4), palpitation(RR=1.28, 95%CI[1.17, 1.41], P<0.000 01), and improved traditional Chinese medicine symptom scores(MD=-4.24, 95%CI[-5.25,-3.23], P<0.000 01) and headache symptom improvement scores(MD=-2.02, 95%CI[-2.51,-1.53], P<0.000 01) as compared with Western medicine group alone. Subgroup analysis results showed that Yang-xue Qingnao Granules combined with ACEI drug had more obvious effects in lowering systolic blood pressure and diastolic blood pressure. There was no statistically significant difference in the incidence of adverse reactions, and no abnormal liver and kidney function was observed in each study. Trial sequential analysis showed that the total effective rate was cumulative across the traditional and TSA thresholds, further confirming its clinical efficacy. The evidence level was mostly low or extremely low in GRADE evaluation. The clinical application of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms is clear and safe, so it is recommended for clinical application.
Antihypertensive Agents/adverse effects* ; China ; Drugs, Chinese Herbal/adverse effects* ; Essential Hypertension ; Humans ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the biomechanical affect of percutaneous transforaminal endoscopic discectomy(PTED) on adjacent segments with different degrees of degeneration and related risk of adjacent segment diseases (ASD) caused by this operation. METHODS: A healthy male adult volunteer was selected, and the lumbosacral vertebra image data was obtained by CT scan, and the external contour of the bone structure was reconstructed. On this basis, the external contour of the bone structure was fitted by using the smooth curve in 3D-CAD software, and the complete three-dimensional finite element modelof the non degenerate L RESULTS: In the finite element model without adjacent segmental disc degeneration, the annulus fibrosus von Mises stress and intradiscal pressure of the PTED model showed only a slight increase under most stress conditions, and a slight decrease in a few conditions, and there was no significant change trend before and after surgery. In the original degenerated adjacent segment disc model, the biomechanical indicators related to disc degeneration in the pre- and post-PTED model showed significant deterioration, leading to an increased risk of potential adjacent spondylopathy. CONCLUSION PTED surgery will not lead to the significant deterioration of postoperative biomechanical environment of non-degeneration adjacent intervertebral discs, and the original degeneration of adjacent intervertebral discs is a important risk factor for ASD.
Adult ; Biomechanical Phenomena ; Diskectomy, Percutaneous ; Finite Element Analysis ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Range of Motion, Articular

In order to improve the supersaturation and maintenance time of drug dispersion in curcumin self-nanoemulsion(CUR-SNEDDS), precipitation inhibitors(PPIs) were introduced to prepare curcumin supersaturated self-emulsion(CUR-SSNEDDS). The composition of CUR-SNEDDS prescriptions was selected through the solubility test, the compatibility of oil phase and surfactant, the investigation of the emulsifying ability of the surfactant and the drawing of the pseudo-ternary phase diagram. Analytic hierarchy process was used in combination with central composite design-response surface method to optimize the prescription. The type and dosage of precipitation inhibitors(PPIs) were selected to maintain the supersaturated concentration and duration of CUR in artificial gastrointestinal fluids. At the same time, polarizing microscope was used to evaluate the crystallization inhibition effect and the quality and in vitro release behavior of CUR-SSNEDDS. The prepared CUR-SSNEDDS prescription was capryol 90-kolliphor RH40-transcutol HP-Soluplus(7.93∶66.71∶25.36∶5), with the drug loading of(65.12±1.25) mg·g~(-1). CUR-SSNEDDS was transparent yellow, and the nanoemulsion droplets were spherical with uniform distribution. The emulsification time was(21.02±0.13) s, the average particle size was(57.03±0.35) nm, the polydispersity index(PDI) was(0.23 ± 0.01), and the Zeta potential was(-18.10±1.30) mV. CUR-SSNEDDS significantly inhibited the generation and growth of crystals after in vitro dilution. The supersaturation could be maintained above 10 within 2 h, and the dissolution rate and degree of CUR in artificial gastrointestinal fluid were significantly increased. Soluplus could effectively maintain the supersaturated state of CUR and enhance CUR dissolution in vitro.
Biological Availability ; Curcumin ; Emulsions ; Nanoparticles ; Particle Size ; Solubility ; Surface-Active Agents

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Arterio-Arterial Fistula ; epidemiology ; China ; epidemiology ; Coronary Angiography ; Coronary Artery Disease ; epidemiology ; Coronary Vessel Anomalies ; Humans ; Prevalence

Aim To investigate the inhibitory effects of the novel compounds YZG-330 and YZG-331 in central nervous system. Methods The sedative effect was investigated by recording the spontaneous locomotor ac-tivity in mice. The hypnotic effect was evaluated by the latency and duration of the loss of righting reflex ( LORR) in the threshold dosage of sodium pentobarbi-tal treated mice. The two compounds induced the mice that had woken up after a threshold dosage pentobarbi-tal sodium to fall asleep again. The levels of GABA and Glu in brain were measured by HPLC-ECD. Re-sults The results showed that spontaneous locomotor activities decreased in YZG-330 (0.125, 0.5,2 mg·kg-1 ) treated mice and YZG-331 (1.25, 5, 20 mg· kg-1 ) treated mice. YZGs could extend the duration of the loss of righting reflex in threshold dosage of sodium pentobarbital treated mice, and significantly shorten sleep latency. YZGs were able to allow the mice that had woken up after a threshold dosage pentobarbital so-dium to fall asleep again. YZG-331 (40 mg·kg-1 ,i. g. ) could significantly increase GABA level in hypo-thalamus and cerebral cortex. The content of GABA had no significant change after YZG-330 ( 2 mg · kg-1 , ig. ) administration. Conclusions YZG-330 and YZG-331 have potent sedative and hypnotic effects. The efficacy of YZG-330 is stronger than that of YZG-331 , but the mechanism of two compounds sounds different.

Asian Continental Ancestry Group ; genetics ; China ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Humans ; Parkinson Disease ; genetics ; Polymorphism, Single Nucleotide