This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L. litseifolius, this study screened out two CHS genes(LlCHS1 and LlCHS2) from the transcriptome data of this plant, and then bioinformatics analysis and functional characterization were performed for the two genes. The bioinformatics analysis showed that LlCHS1 and LlCHS2 were acidic hydrophilic stable proteins with no transmembrane domain, composed of 395 and 390 amino acid residues, respectively. Both of them contained the characteristic amino acid sequence "WGVLFGFGPGL" and highly conserved active sites(Cys-164, Phe-215, His-303, and Asn-336) of the CHS family. The phylogenetic tree showed that LlCHS1 shared the same clade with similar genes in Aquilaria sinensis, and LlCHS2 was closely related to similar genes in Malus domestica. Under exogenous addition of phloretic acid, co-expression of LlCHS1 or LlCHS2 with Aa4CL from Aromatoleum aromaticum in Escherichia coli catalyzed the production of phloretin from phloretic acid. This study laid a theoretical foundation for revealing the functions of CHS in plants and provided new enzymatic modules for producing phloretin by synthetic biology.
Acyltransferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Cloning, Molecular ; Amino Acid Sequence

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Animals ; Rats ; Caspase 1/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-18 ; Blood Glucose ; Pyroptosis ; Tumor Necrosis Factor-alpha ; Diabetes Complications ; Vascular Diseases ; Inflammasomes ; Cholesterol ; Lipids ; Diabetes Mellitus

Background: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. Methods: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. Results: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ² = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. Conclusion: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. Trial Registration NCT01962155; https://clinicaltrials.gov.

OBJECTIVETo observe the clinical effects of retrograde intramedullary nailing and cannulated screws in the treatment of femoral condylar fracture.

METHODSFrom June 2009 to June 2015, 13 patients with femoral condyles fracture were treated by retrograde intramedullary nailing and cannulated screws including 6 males and 7 females with an average age of 46.1 years old ranging from 16 to 76 years old. There were 10 cases of closed fractures, 3 cases of open fraetures. According to AO classification criteriam, 4 cases were type C1, 7 cases were type C2, 2 cases were type C3. Postoperative reduction of fracture and the knee joint function recovery were observed.

RESULTSAll patients were followed up for 12 to 36 months with a mean of 24 months. X-ray examination showed that the union time of fracture was 18 to 24 weeks, 21 weeks on average. There were no cases of loosening, breakage of internal fixators and re-fracture. Hospital for Special Surgery(HSS) knee score was 90.07±4.99 at 1 year after the operation.

CONCLUSIONSThe clinical efficacy for retrograde intramedullary nailing and cannulated screw for the treatment of femoral condyles fracture was excellent. It can improve the anatomical reattachment rate and reduce the complications and promote the knee functional recovery.

To investigate the inhibitory mechanism of quercetin on growth of human bladder cancer cell line(BIU-87). BIU-87 cells were cultured in vitro, and co-cultured with varying concentrations of quercetin, and the anti-proliferative activity was determined by CCK-8 assay. Apoptosis of quercetin-induced BIU-87 cells and cell cycle were determined by flow cytometry analysis. Expressions of Bal-2 and Bal-xL, and related proteins in TAK1/JNK signal pathway were measured using Western blot analysis. After treatment with quercetin for 24 h and 48 h, the proliferation of BIU-87 cells was significantly suppressed in a dose-dependent manner according to CCK-8 assay(P<0.05). The flow cytometry analysis indicated that each group of quercetin leads to a significant higher percentage of apoptosis of BIU-87 cells than control group after treatment with quercetin for 24 h and 48 h; In G₀/G₁ period, cells reduced, while the amount of cells in G₂/M period increased, and cells in S period remained the same amount. Expressions of Bal-2, Bal-xL, p-TAK1, p-MKK4/7, p-JNK decreased in BIU-87 cells after treatment with quercetin. Quercetin could inhibit the proliferation and promote the apoptosis of BIU-87 cells. The mechanism may be correlated with the inhibition of TAK1/JNK signaling pathway, which led to the further decrease in expressions of Bal-2 and Bal-xL.

OBJECTIVETo observe the effect and safety of Xiaozhi particles, integrated taohong Siwu tang and Erchen tang and Xuezhikang capsule in treating hyperlipidaemia (HLP) associated with highly active antiretroviral therapy (HAART).

METHODIn the multi-centered, randomized controlled clinical study, 180 hyperlipidaemia associated with highly active antiretroviral therapy cases were divided into the treatment group treated by Xiaozhi particles, integrated Taohong Siwu tang and Erchen tang, and the control group treated by Xuezhikang capsule. The treatment course was 12 weeks. The total cholesterol (Tch), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein(HDL) were observed.

RESULTAfter 12 weeks, compared with Xuezhikang capsule, the change difference of Tch, LDL, HDL in the Chinese traditional medicine formula groups of patients is significant (P < 0.05), the change of the TG has no significant difference. The effect of Tch, LDL in Xuezhikang capsule groups is better than in traditional Chinese medicine formula group,but the effect of HDL in traditional Chinese medicine formula group is better than in Xuezhikang capsule groups.

CONCLUSIONIntegrated Taohong Siwu tang and Erchen tang, Xiaozhi particles and Xuezhikang capsule can be used to control the hyperlipidaemia associated with highly active antiretroviral therapy as one of the main Chinese native medicine preparation.

Adult ; Antiretroviral Therapy, Highly Active ; adverse effects ; Cholesterol ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Hyperlipidemias ; blood ; chemically induced ; drug therapy ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Triglycerides ; blood

OBJECTIVETo compare the stability of sacroiliac screws fixation for the treatment of bilateral vertical sacral fractures to provide reference for clinic application.

METHODSA finite element model of Tile C pelvic ring injury (bilateral type Denis II fracture of sacrum) was produced. The bilateral sacral fractures were fixed with sacroiliac screws in 4 types of models respectively: two bidirectional sacroiliac screws fixation in the S₁ segment, two bidirectional sacroiliac screws fixation in the S₂ segment, one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment, two bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively. By the ABAQUS 6.9.1 software, in the case of standing on both feet, 600 N vertical load was imitated to be imposed to the superior surface of the sacrum and downward translation and backward angle displacement of the middle part of the sacral superior surface and everted angle displacement of the top of iliac bones were extracted for analysis. The stability of sacroiliac screws fixation was compared according to the principle of the better stability the smaller displacement.

RESULTSThe stability of 2 bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively was markedly superior to that of 2 bidirectional sacroiliac screws fixation in S₁ or S₂ segment and was also markedly superior to that of one sacroiliac screw fixation in S₁ segment and one sacroiliac screw fixation in S₂ segment. The vertical and everted stability (the downward translation: 0.531 mm; the everted angle displacement: 0.156° (left side), 0.163° (right side)) of sacroiliac screws fixation in two bidirectional sacroiliac screws fixation in the S₂ segment was superior to that of two bidirectional sacroiliac screws fixation in the S₁ segment (the downward translation: 0.673 mm; the everted angle displacement: 0.200° (left side), 0.232° (right side)). The rotational stability of two bidirectional sacroiliac screws fixation in the S₁ segment (the backward angle displacement: 0.269°) was superior to that of two bidirectional sacroiliac screws fixation in the S₂ segment (the backward angle displacement: 0.287°). Moreover, the rotational stability of one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment was inferior to that of two bidirectional sacroiliac screws fixation in the S₁ segment or two bidirectional sacroiliac screws fixation in the S₂ segment, and the vertical and everted stability of one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment was between that of two bidirectional sacroiliac screws fixation in the S₁ segment and two bidirectional sacroiliac screws fixation in the S₂ segment.

CONCLUSIONSTwo bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively is recommended to be utilized for fixing bilateral sacral fractures of Tile C pelvic ring injury as far as possible. It is suggested to choose sacral segments in which sacroiliac screws fixed according to vertical, rotational and everted stability degree of sacral fractures.

Adult ; Bone Screws ; Computer Simulation ; Female ; Finite Element Analysis ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Sacrum ; injuries ; surgery

Objective To evaluate the effects of socioeconomic status on the distribution of cardiovascular risk factors and clinical treatments of patients with acute myocardial infarction in Beijing.Methods In Beijing, a prospective, muhi-center, registration study was carried out which including 800 patients who were consecutively hospitalized for ST-segment elevation acute myocardial infarction within 24 hours after event attack in 19 different hospitals in Beijing between November, 2005 and December, 2006.Indicators of socioeconomic status included self-reported personal income (＜500, 500-2000,＞2000 RMB/month), educational attainment (≤ 12 and ＞ 12 years) and status of medical insurance (yes/no).According to categories of education, patients were categorized into two groups of lower socioeconomic status and higher socioeconomic status. Differences of cardiovascular risk factors and clinical treatments were compared across the two groups respectively. Results Proportion of diabetes and hyperlipidemia in patients with higher socioeconomic status was much higher than that of patients with lower socioeconomic status (P＜0.05, P＜0.01 respectively). Patients with lower socioeconomic status were more likely to be smokers (P ＜0.05). The rates of receiving coronary angiography and PTCA were much lower in patients with lower socioeconomic status. Medical insurance and income were the most important two socioeconomic factors determining the use of PTCA. Conclusion Compared to patients with lower socioeconomic status,patients with higher socioeconomic status had higher rates of hyperlipidemia and diabetes but lower smoking rate among cardiovascular risk factors. The rates of receiving interventional therapies were much lower in patients with lower socioeconomic status.

Erectile dysfunction is a common disease of andrology, for which current guidelines recommend oral agents as the first-line therapy. The dopamine agonist apomorphine acts on the central control of penile erection to allow a sublingual preparation to produce a prompt response. It is not contraindicated in patients on nitrate medication for coronary artery disease. The present review describes the pharmacodynamics, action mechanism, efficacy and adverse effects of apomorphine.
Apomorphine ; adverse effects ; pharmacokinetics ; therapeutic use ; Dopamine Agonists ; adverse effects ; pharmacokinetics ; therapeutic use ; Erectile Dysfunction ; drug therapy ; physiopathology ; Humans ; Male ; Penile Erection ; drug effects