OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis （AS）based on macrophage polarization. METHODS Using atorvastatin served as the positive control， the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability， apoptosis rate， and the fluorescence intensities of CD86 and CD206 were measured， along with the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Apolipoprotei n E-deficient （ApoE －/－ ） mice （AS model mice） fed with a high-fat diet were randomly assigned to model group， atorvastatin group （2.6 mg/kg）， and low-， medium- and high-dose groups of Qingre huatan huoxue decoction （90， 180， 360 mg/kg）， respectively. C57BL/6J mice fed with a standard diet served as the normal control group， with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically， once daily， for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta （assessed by the percentage of plaque in the entire aorta and aortic root） and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue， as well as the protein expression levels of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， AMP-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， and peroxisome proliferator-activated receptor γ （PPAR-γ） in aortic tissues were all detected. RESULTS Cell experiment results showed that， at concentrations of 5-100 μg/mL， the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability （ P ＜0.05）. The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10， 50， and 100 μg/mL， along with atorvastatin， significantly reduced apoptosis rates， CD86 fluorescence intensity， and TNF-α and IL-1β levels in RAW264.7 cells， while markedly enhancing CD206 fluorescence intensity （ P ＜0.05）. Animal experiment results showed that， compared with the model group， all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum， along with decreased aortic total and root plaque percentages， CD86 expression， and iNOS protein expression. CD206 expression and Arg-1， p-AMPK/AMPK， PPAR-γ protein expression were significantly up-regulated （ P ＜0.05）. Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization， increasing the proportion of M2 macrophages， thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.

Severe insulin resistance syndrome associated with mutations in the insulin receptor(INSR) gene is rare in clinical practice. We report a 13-year-old female patient with insulin resistance, acanthosis nigricans, and Class Ⅱ malocclusion, whose family history included hyperinsulinemia in both her mother and grandmother. Whole-exome sequencing and PCR-Sanger validation identified a novel INSR mutation, c. 637delA(p.S213Vfs*69), resulting in a pathogenic variant that substitutes serine at position 213 with valine. This case highlights a clinical phenotype that is challenging to differentiate between Rabson-Mendenhall syndrome and A-type insulin resistance syndrome. Long-term follow-up is crucial to assess disease progression and prognosis.

Objective To solve the problem of large data volume,multiple dimensions and low value for assisting traditional Chinese medicine clinical diagnosis in home health perception layer devices.Methods Based on the principles of traditional Chinese medicine diagnosis,this paper divides home health data into three types:complementary,redundant,and collaborative,and proposes a solution for data fusion at the levels of device data,home events,and traditional Chinese medicine symptoms.Results The proposed data fusion solution in this paper enables the data collected by various devices in the home environment to work together,extracts home data that is more valuable for traditional Chinese medicine diagnosis,and reduces the real-time pressure on the home network bandwidth caused by the sensors on the home side.Conclusion The construction of an open IoT ecosystem for home health based on multiple devices is a huge project,which includes the construction of perception layer hardware,data cleaning,fusion,normalization,labeling,modeling,and other aspects.This paper focuses on the idea of home health data fusion,which can provide directions for cleaning up heterogeneous data from multiple sources at home and also provide ideas for subsequent data labeling and modeling with traditional Chinese medicine characteristics,thus providing more valuable decision-making assistance for traditional Chinese medicine clinical practice.

Severe insulin resistance syndrome associated with mutations in the insulin receptor(INSR) gene is rare in clinical practice. We report a 13-year-old female patient with insulin resistance, acanthosis nigricans, and Class Ⅱ malocclusion, whose family history included hyperinsulinemia in both her mother and grandmother. Whole-exome sequencing and PCR-Sanger validation identified a novel INSR mutation, c. 637delA(p.S213Vfs*69), resulting in a pathogenic variant that substitutes serine at position 213 with valine. This case highlights a clinical phenotype that is challenging to differentiate between Rabson-Mendenhall syndrome and A-type insulin resistance syndrome. Long-term follow-up is crucial to assess disease progression and prognosis.

Objective:To establish a mouse model of intra-jugular arteriovenous fistula (AVF) to screen differentially expressed genes in the process of intimal stenosis of AVF for investigating the abnormal expression signaling pathways and the mechanisms.Methods:Forty-six male C57BL/6 mice were randomly divided into AVF group ( n=23) and sham-operated group ( n=23). The AVF group underwent internal jugular arteriovenous fistuloplasty, and the sham-operated group separated the right external jugular vein and common carotid artery and then sutured the incision. The whole-genome sequences of mice with AVF stenosis were determined by transcriptomic reversible chain terminator and synthetic sequencing. The microarray data set was established, and the Benjamini & Hochberg method of gene microarray data analysis was applied to screen the differentially expressed genes. The differentially expressed genes were screened by R-language enrichment analysis. Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were performed. The subcellular localization of the differentially expressed genes was performed by BUSCA software. The protein network interaction of differentially expressed genes was analyzed by using STRING database and Cytoscape software. Results:In the AVF group, 21 mice were successfully modeled and 2 mice failed. Therefore, there were 21 mice in the AVF group and only 21 mice in the sham-operated group. This mouse internal jugular AVF model was innovated using the continuous-interrupted suture method, which improved the success rate of modeling this model. The differential gene sequencing analysis showed that there were 2 514 differentially expressed genes in the AVF process, including 1 323 up-regulated genes and 1 191 down-regulated genes. GO functional enrichment analysis showed that the differential genes were mainly enriched in metabolic process, activation, redox, mitochondria and so on. KEGG pathway enrichment analysis showed that the differential genes were enriched in metabolism, energy substance synthesis, diabetes, oxidative stress and so on. Statistical analysis of subcellular localization showed that the differences were mainly in mitochondrial proteins (24.24%), cytoplasmic proteins (17.51%), nuclear proteins (13.13%), cell membrane proteins (11.45%), and extracellular proteins (10.77%).Conclusions:Mitochondrial oxidative stress injury may be involved in the pathological damage process of endothelial proliferation stenosis in the AVF.

Objective:Clamping bilateral renal arteries with refined surgical methods to establish the rat renal ischemia-reperfusion injury (RIRI) model, and study the protective mechanism of ischemic preconditioning renal (IPC) tubular cell-derived exosomes in RIRI.Methods:25 female Sprague Dawley (SD) rats were divided into sham group, model group, inactivated group, normoxic group, IPC group. In the sham operation group, after bilateral renal arteries were dissociated, the back incision was disinfected and closed. The model group established RIRI model; RIRI models were established in inactivated group, normoxia group and IPC group, and then 200 μg of inactivated exosomes, normal exosomes and IPC exosomes were injected into the caudal vein 24 hours after operation. Serum creatinine (Scr) and urea nitrogen (BUN) levels were detected. The pathological changes of renal tissue were observed under light microscope. Transmission electron microscopy (TEM) was used to observe the shape and size of renal tubular exosomes. Nanoparticle tracking analysis (NTA)was used to detect the concentration and size of renal tubular exosomes.Results:Compared with the sham group, the Scr and BUN levels in the model group were significantly elevated ( P<0.01). Renal pathological changes in the model group showed damaged of the tubular structure, necrosis and shedding of tubular epithelial cells, and a large number of inflammatory cells accumulated in the renal interstitial tissue with varying degrees of edema. Compared with the inactivated group, the Scr and BUN levels significantly decreased in the normoxic group and IPC group ( P<0.01). Renal pathological changes in the normoxic group and IPC group showed that the renal tubular cell necrosis alleviated, inflammatory was reduced, the improved edema. Compared with the normoxic group, the Scr and BUN levels in the IPC group were further reduced ( P<0.01). Renal pathological changes in the IPC group showed that the inflammatory cells were significantly reduced, the cell edema was significantly improved, and the cell apoptosis was significantly reduced. Conclusions:Clamping bilateral renal arteries with refined surgical methods is the main and optimal way to build a rat model of RIRI. IPC tubular cell-derived exosomes have protective and repair effects on RIRI.

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Objective:To investigate the effects and underlying mechanisms of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/NF-κB signaling pathway in human kidney-2(HK-2) cells of hyperuricemic nephropathy.Methods:HK-2 cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was induced by high uric acid (720 μmol/L) immersion for 48 h to establish a cell model of hyperuricemic nephropathy in vitro and subsequently divided into hyperuricemic group, overexpressed protease activated receptor 2 (PAR2) and knockdown PAR2 group. The expressions of PAR2, PI3K, AKT, NF-κB mRNA were measured by real-time PCR. The expressions of PAR2, PI3K, AKT and NF-κB protein were measured by Western blotting. The expressions of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), pro-interleukin-1β (pro-IL-1β), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) were detected by enzyme linked immunosorbent assay (ELISA). Results:(1) Compared with the control group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in hyperuricemic group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant in hyperuricemic group were significantly increased (all P<0.01). (2) Compared with the hyperuricemic group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in overexpressed PAR2 group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, IL-1β and TGF-β1 in the supernatant were significantly increased (all P<0.05). (3) Compared with the hyperuricemic group, the expression of PAR2, PI3K, AKT and NF-κB mRNA and protein in knockdown PAR2 group were significantly decreased (all P<0.05), the expressions of IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant were significantly decreased (all P<0.05). Conclusions:In the process of uric acid-induced HK-2 cell damage, uric acid significantly up-regulates the expression of PI3K/AKT/NF-κB signaling pathway by activating PAR2, leading to a marked increase in inflammatory damage. Knocking down PAR2 inhibits the expression of PI3K/AKT/NF-κB signaling pathway, which can effectively reduce the inflammatory damage of HK-2 cells.

Objectives To observe the effect of low intensity pulsed ultrasound (LIPUS) on osteocyte injuries induced by the tricalcium phosphate(TCP) wear particles in the calvaria of mice.Methods Thirty ICR male mice of 6 to 8 weeks were randomly divided into a normal control group(n=10),a model group (n=10) and a LIPUS-treated group(n=10).A murine calvarial model of osteolysis was established in the model and LIPUS-treated groups through injecting TCP particles onto the surface of bilateral parietal bones at week 1,3,5,7 and 11.Mice in the normal group received negative ultrasound probe pressing,while those in the LIPUS-treated received LIPUS radiation.Three months later,the calvarias were obtained.The micro-CT,HE staining,flow cytometry and Western blotting were performed to estimate the calvarial osteolysis,osteocyte death,apoptosis and proteins expression of the dentin matrix protein 1 (DMP-1),sclerosis protein (SOST),glucose-regulated protein78 (GRP78),inositol-requiring enzyme(IRE 1 α),spliced X-box binding protein 1 (XBP1 s),c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase(p-JNK) respectively.Results Compared with the normal control group,in the model group the viability of prosthetic osteocytes decreased significantly,and cell apoptosis was more obvious(P＜0.05);the osteocytic marker protein DMP-1 down-regulated significantly,but another marker protein SOST up-regulated significantly,which caused the decline in DMP-1/SOST(P＜0.05).Moreover,the expression levels of GRP78,IRE1,XBPls and p-JNK of the model group increased significantly(P＜0.05) in the calvaria osteocytes compared to the control group.However,in the LIPUS treatment group,osteocyte injuries and endoplasmic reticulum(ER) stress both decreased significantly,shown by a significant increase in the number and activity of osteocytes,DMP-1/SOST,and significant inhibition of the IRE1α-XBP1-JNK activation(P＜0.05).Conclusion LIPUS prevents osteocyte injuries induced by TCP wear particles in the calvaria of mice,which may be due to the inhibition of IRE1α-XBP1-JNK pathway activation through ER stress reaction.

OBJECTIVETo investigate the perioperative benefit of suprapubic cystostomy in bipolar transurethral resection of the prostate (B-TURP) for treatment of benign prostatic hyperplasia (BPH) below 80 g.

METHODSThis retrospective study was conducted in patients undergoing B-TURP for BPH below 80 g, who were stratified with respect of suprapubic cystostomy in B-TURP. The end points including the safety, efficiency, complications and nursing care were compared between the two groups.

RESULTSA total of 585 patients were enrolled, including 366 in cystostomy group and 219 in non-cystostomy group. The two groups showed similar postoperative reduction of serum sodium (0.06 vs 0.54 mmol/L, P>0.05), hematocrict (2.44% vs 2.89%, P>0.05), and blood hemoglobin concentration (9.62 vs 10.42 g/L, P>0.05), with comparable weight of resected prostate (42.50 vs 43.76 g, P>0.05). The operation time was significantly longer in cystostomy group than in non-cystostomy group (90.75 vs 76.28 min, P<0.05), but the rate of blood transfusion and incidences of postoperative fever and catheter blocking were comparable between the two groups. Compared with the non-cystostomy group, cystostomy group had significantly longer time for bladder washing (3.15 vs 2.57 days, P<0.05), catheter indwelling time (5.19 vs 4.15 days, P<0.05), and hospital stay after the operation (7.36 vs 5.65 days, P<0.05).

CONCLUSIONSIn B-TURP for BPH below the weight of 80 g, suprapubic cystostomy is associated with a longer time for operation, bladder washing, catheter indwelling and postoperative hospital stay, and thus provides no obvious benefits for the patients.

Catheters, Indwelling ; Cystostomy ; Hemoglobins ; Humans ; Length of Stay ; Male ; Operative Time ; Postoperative Period ; Prostatic Hyperplasia ; surgery ; Retrospective Studies ; Transurethral Resection of Prostate ; Treatment Outcome ; Urinary Bladder