The effects of mangiferin on uric acid excretion, kidney function and related renal transporters were investigated in hyperuricemic mice induced by potassium oxonate. Mice were divided into normal control group, and 5 hyperuricemic groups with model control, 50, 100, and 200 mg x kg(-1) mangiferin, and 5 mg x kg(-1) allopurinol. Mice were administered by gavage once daily with 250 mg x kg(-1) potassium oxonate for seven consecutive days to create the model. And 3 doses of mangiferin were orally initiated on the day 1 h after potassium oxonate was given, separately. Serum uric acid, creatinine and urea nitrogon levels, as well as urinary uric acid creatinine levels were measured. Mouse uromodulin (mUMOD) levels in serum, urine and kidney were determined by ELISA method. The mRNA and protein levels of related renal transporters were assayed by RT-PCR and Western blotting methods, respectively. Compared to model group, mangiferin significantly reduced serum uric acid, creatinine and urea nitrogon levels, increased 24 h uric acid and creatinine excretion, and fractional excretion of uric acid in hyperuricemic mice, exhibiting uric acid excretion enhancement and kidney function improvement. Mangiferin was found to down-regulate mRNA and protein levels of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9), as well as up-regulate organic anion transporter 1 (mOAT1) in the kidney of hyperuricemic mice. These findings suggested that mangiferin might enhance uric acid excretion and in turn reduce serum uric acid level through the decrease of uric acid reabsorption and the increase of uric acid secretion in hyperuricemic mice. Moreover, mangiferin remarkably up-regulated expression levels of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2), increased urine mUMOD levels, as well as decreased serum and kidney mUMOD levels in hyperuricemic mice, which might be involved in mangiferin-mediated renal protective action.

This study was aimed to investigate renal protective effects and mechanism of Gui-Zhi(GZ) decoction in hyperuricemic mice.Potassium oxonate was used to induce hyperuricemia mouse model.Mice were randomly divided into 6 groups,which were the blank control group,model group,allopurinol group (5 mg·kg-1) and GZ decoction group (900,1 799 and 3 598 mg·kg-1).Hematoxylin eosin staining was used to observe the histopathological changes of renal tissues in mice.Commercial assay kits were used to measure levels of uric acid (UA),creatinine (Cr) and blood urea nitrogen (BUN) in serum and urine,as well as the xanthine oxidase (XOD) activity in liver.Renal protein levels of urate transporter 1 (URAT1),glucose transporter 9 (GLUT9),ATP-binding cassette G member 2 (ABCG2),organic cation transporter 1 (OCT1),OCT2,organic cation/carnitine transporter 1 (OCTN1) and OCTN2 were detected by western blot.The results showed that compared with the model group,GZ decoction can obviously decrease serum levels of UA,Cr and BUN,increase urine levels of UA and Cr,resulting in the elevation of fractional excretion of UA in hyperuricemic mice.Additionally,GZ decoction obviously inhibited hepatic XOD activity in hyperuricemic mice.Furthermore,GZ decoction downregulated renal URAT1 and GLUT9 protein levels,upregulated renal ABCG2,as well as OCT1,OCT2,OCTN1 and OCTN2 protein levels in hyperuricemic mice.It was concluded that GZ decoction had hypouricemic and renal protective effects in hyperuricemic mice,which might be associated with the reduction of UA production via inhibiting hepatic XOD activity,promoting UA and other organic ion excretion via regulating renal organic ion transporter protein levels.

By analyzing the related indicators [hepatic CYP450 subtype and renal organic anion and cation transporters (OATs and OCTs)], the present study investigated the effects of formula Banxia Houpo decoction principal drug pinellia, assistant drug magnolia, their compatibility and the principle of the whole decoction on the metabolism ability in the liver and the transport change in the kidney of mice. Biochemical and molecular (RT-PCR and western blotting) results indicated that pinellia increased activity and expression of hepatic Cyp2e1 and Cyp3a11 in mice, respectively. Pinellia and magnolia increased expression of renal OAT1, OAT3, OCT1 and OCT2 in mice, respectively. The compatibility of pinellia and magnolia, as well as Banxia Houpo decoction synergistically restrained the activated effect of pinellia on hepatic Cyp2e1, therefore avoiding liver peroxidation and reducing toxicity potential. The compatibility of this drug pair and Banxia Houpo decoction not only reduced activity and expression of hepatic Cyp3a11 to control drug metabolism speed, but also balanced the expression of renal OAT1/3 and OCT1/2 to enhance drug efficacy. The effect of compatibility of Banxia Houpo decoction was better than that of pinellia and magnolia pair, and the normal dosage was better than the high dosage. The present study proved the advantage of the compatibility of pinellia combined with magnolia and the principle of Banxia Houpo decoction, which related to hepatic CYP450 and renal organic ion transporters, and guided the clinical use of Banxia Houpo decoction to exert its toxicity reduction and efficacy enhancement.
Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Mice ; Organic Anion Transporters ; genetics ; metabolism

OBJECTIVE: To evaluate the diagnostic accuracy of a dual-source computed tomography (DSCT) coronary angiography, with a particular focus on the effect of heart rate and calcifications. MATERIALS AND METHODS:One hundred and nine patients with suspected coronary disease were divided into 2 groups according to a mean heart rate (< 70 bpm and > or = 70 bpm) and into 3 groups according to the mean Agatston calcium scores (< or = 100, 101-400, and > 400). Next, the effect of heart rate and calcification on the accuracy of coronary artery stenosis detection was analyzed by using an invasive coronary angiography as a reference standard. Coronary segments of less than 1.5 mm in diameter in an American Heart Association (AHA) 15-segment model were independently assessed. RESULTS: The mean heart rate during the scan was 71.8 bpm, whereas the mean Agatston score was 226.5. Of the 1,588 segments examined, 1,533 (97%) were assessable. A total of 17 patients had calcium scores above 400 Agatston U, whereas 50 had heart rates > or = 70 bpm. Overall the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for significant stenoses were: 95%, 91%, 65%, and 99% (by segment), respectively and 97%, 90%, 81%, and 91% (by artery), respectively (n = 475). Heart rate showed no significant impact on lesion detection; however, vessel calcification did show a significant impact on accuracy of assessment for coronary segments. The specificity, PPV and accuracy were 96%, 80%, and 96% (by segment), respectively for an Agatston score less than 100% and 99%, 96% and 98% (by artery). For an Agatston score of greater to or equal to 400 the specificity, PPV and accuracy were reduced to 79%, 55%, and 83% (by segment), respectively and to 79%, 69%, and 85% (by artery), respectively. CONCLUSION: The DSCT provides a high rate of accuracy for the detection of significant coronary artery disease, even in patients with high heart rates and evidence of coronary calcification. However, patients with severe coronary calcification (> 400 U) remain a challenge to diagnose.
Calcinosis/*radiography ; Coronary Angiography/methods/*standards ; Coronary Disease/*radiography ; Coronary Vessels/*pathology ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Tomography, X-Ray Computed/methods/*standards

Objective: To investigate the efficacy of periprocedural use of bivalirudin for patients with chronic total occlusion(CTO) lesion undergoing percutaneous coronary intervention(PCI) therapy. Methods: In this randomized controlled study, 74 patients with CTO lesions confirmed by coronary angiography or CT angiography, hospitalized in the general hospital of Shenyang military region from September 2015 to December 2016, were randomly divided into unfractionated heparin(UFH) group (n=38) and bivalirudin group (n=36) by the random number table.Patients in the UFH group were treated with injection of UFH 5 000 U through the artery sheath catheter before coronary angiography,and the UFH was intravenously administered at 100 U/kg before PCI. Patients in the bivalirudin group received intravenous injection of bivalirudin (0.75 mg/kg) before coronary angiography, followed by intravenous infusion of 1.75 mg·kg^-1·h^-1 until at least 2 hours after the PCI. The values of the activated coagulation time (ACT) were measured,and the value was remained at 250 to 350 seconds during the PCI. The incidence rate of adverse events including hemorrhage events, no-reflow/slow flow, and contact thrombus in perioperative period were observed in all patients. In addition, the incidence rate of the major adverse cardiovascular events (MACE) including recurrent angina, heart failure, target vessel revascularization, cardiac death, non-fatal myocardial infarction,and stroke within 1 year follow-up period were also observed in the 2 groups. Results: Baseline clinical and PCI data were similar between the 2 groups (all P>0.05). During the perioperative period, the incidence of the bleeding was significantly lower in the bivalirudin group than in the UFH group(5.6% (2/36) vs. 23.7% (9/38) , P=0.028).The incidence of no-reflow/slow flow was also significantly lower in the bivalirudin group than in the UFH group(0 vs. 15.8% (6/38) , P=0.025). There was no significant difference in the incidence of contact thrombosis between bivalirudin group and UFH group(8.3% (3/36) vs. 0, P=0.110). There was no cardiac death or non-fatal myocardial infarction in the 2 groups within 1 year after PCI, and there was no significant difference in the incidence of MACE in 1 year follow-up after operation between bivalirudin group and UFH group (11.1% (4/36) vs. 21.1% (8/38) , P=0.246). Conclusion The application of the anticoagulant bivalirudin during PCI in patients with CTO lesion can reduce the incidence of perioperative bleeding and no-reflow/slow flow, and does not increase the risk of MACE within 1 year after PCI.

On the basis of the existing appointment process, artificial intelligence and Internet of things technologies were introduced to optimize such process. Thanks to the all appointment process management empowered by AI and IoT, patient waiting time is cut short and patient satisfaction enhanced as a result.

Objective To evaluate the effects of nasolabial flap with facial artery and its branches perforator for reconstruction of nasal defect.Methods Between March 2013 and April 2017,21 patients underwent operations for the reconstruction of nasal defect,caused by trauma,surface tumors,moles and infection.The size of the defect was 1.5 cm × 2.0 cm to 3.0 cm × 3.0 cm.Designed various nasolabial perforator flap was pedicled with the facial artery.The pulsed blood flow detector determined the location of the facial artery and its perforation position,which was the rotation point,and the rotation of the nasolabial fold flap covered the nasal defect area to repair.Results 21 flaps survived.Surface artery perforation nasolabial fold flap was good blood supply,of which 1 case of flap was congested and recovered after treatment.After 1 month to 3 years follow-up on 21 cases,20 cases showed good results and 1 case had generally accepted.The color,shape and function of the flap were significant,similar to the normal skin.Conclusions A small area defect in the nose is preferred by using facial arterial perforation nasolabial fold flap repair,which does not need secondary repair,and is worthy of clinical application.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.