TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Construction of prognostic risk model of bladder cancer based on cuproptosis-related long non-coding RNAs / 浙江大学学报·医学版

OBJECTIVES@#To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients.@*METHODS@#RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves.@*RESULTS@#A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8+ T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all P<0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both P<0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value.@*CONCLUSIONS@#A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.

Advances in understanding leukemia bone marrow microenvironments / 药学学报

The bone marrow microenvironment, also known as the bone marrow niche, plays a critical role in maintaining the functions of hematopoietic stem cells. Under physiological conditions, various bone marrow cells regulate each other to sustain hematopoietic homeostasis. However, bone marrow cells gain abnormal function under pathological conditions to cause and promote the occurrence of leukemia and induce drug resistance. Recent findings indicate that abnormal proliferation and differentiation are not the sole reason to cause leukemia. Different types of bone marrow cells also induce intercellular adhesion, abnormally secrete cytokines and chemokines, accelerating leukemia's progress. This article reviews the multiple signaling pathways that regulate the formation and progress of leukemia bone marrow niche, such as C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 signaling pathway, et al. It emphasizes that targeting leukemia bone marrow niche is a vital strategy for improving the leukemia treatment.

Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients / 中国中药杂志

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

TRIB3 promotes lung cancer cell survival and inhibits apoptosis through NRF2 activation / 药学学报

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

Research progress of glucagon receptor related compounds / 药学学报

Type 2 diabetes is a complex metabolic disease, accompanied by insulin resistance and elevated blood glucose. As the disease progresses, hyperglucagonemia will occur. Glucagon has a significant effect on glucose increase and energy expenditure. In recent years, several glucagon receptor (GCGR) antagonists were developed. They lowered blood glucose in clinical studies, along with side effects, such as increased blood lipids and elevated liver transaminase. In order to solve these problems, glucagon like peptide 1 receptor (GLP-1R)/GCGR co-agonists were developed, which not only lower blood glucose, but also reduce weight and promote lipolysis. In this review, we will focus on the biological effects of glucagon, the treatments of GCGR antagonists, and GLP-1R/GCGR co-agonists on type 2 diabetes.

TRIB3‒GSK-3

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3

Characterization and Antioxidant Activities of Polysaccharide Isolated fromLinggui Zhugan Tang / 中国实验方剂学杂志

Objective:To characterize the structure of polysaccharide isolated from Linggui Zhugan Tang（LGZGT）,including monosaccharide composition and functional group detection, investigate the difference of the antioxidant activities of crude polysaccharide（CP） and pure polysaccharide（PP）, and provide the basis for the quality evaluation of LGZGT by in vitro bioassay. Method:The average molecular weight of CP was analyzed by high performance gel chromatography（HPGPC）. Gas chromatography-mass spectrometry（GC-MS） and fourier transform infrared（FT-IR） were employed to determine the structure of the polysaccharide. The antioxidant activities of CP and PP samples were evaluated on the basis of 1-diphenyl-2-picrylhydrazyl（DPPH） radical scavenging activity and OH radical scavenging activity. Result:The total polysaccharide was composed of single peaks, with a molecular weight of 3 689 Da. It was mainly composed of arabinose, mannose, glucose, galactose and fructose with a molar ratio of 6.85∶1.00∶109.21∶1.04∶21.82. Among them，glucose and fructose were the predominant components. In addition， IR study indicated the presence of pyranose and anomeric configurations in glycan structure, with two stereoisomers of glycosidic bond (α-glycosidic bond and β-glycosidic bond). It was found that the total polysaccharide had the ability of scavenging DPPH and hydroxyl radicals, and the activity of crude polysaccharide was better than that of refined polysaccharide. It was found in antioxidant research that the total polysaccharide had the ability of scavenging DPPH and hydroxyl radicals, and the activity of CP was better than that of PP. Furthermore, LC-Q-TOF-MS was used to qualitatively analyze the other components in CP, which indicated that it was related to the adsorption of pentacyclic triterpenoids in Glycyrrhiza uralensis. Conclusion:The polysaccharides and pentacyclic triterpenoids in LGZGT are the material basis for the antioxidative effect of LGZGT. The antioxidative activity determined by in vitro bioassay can be used as an evaluation index for the overall quality control of LGZGT.

Research progress on the role of bile acids in regulating glycolipid metabolism / 药学学报

Bile acids (BAs) are increasingly being appreciated as signaling molecules. Studies have shown that BAs regulate glucose and lipid metabolism mainly through the intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed in the intestine. This article summarizes the synthesis, circulation, and regulation of BAs, as well as the effects of BAs on glycolipid metabolism through activation of liver FXR and inhibition or activation of intestinal FXR and TGR5. Furthermore, we illustrate the molecular mechanism of BAs on glycolipid metabolism by the relevant signaling pathways, including small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19), ceramide and glucagon like peptide-1 (GLP-1). This review may serve as a reference for basic and clinical studies.

Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting

Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.

UFLC-Q-TOF-MS fingerprints of rhizome of Curcuma phaeocaulis and its vinegar processed products and inhibitory effect on thrombosis / 中国中药杂志

Both raw and vinegar products of the rhizome of Curcuma phaeocaulis are common drugs for promoting blood circulation and removing blood stasis in traditional Chinese medicine,which could be reflected in the inhibition of tail thrombosis in mice. As the traditional processing theory instructs,vinegar tastes sour and bitter,but can activate blood circulation and remove stasis after being infiltrated into the rhizome of C. phaeocaulis as an excipient. In this study,under the help of the ultrafast liquid chromatography-quadrupole time-offlight mass spectrometry( UFLC-Q-TOF-MS),the spectrum-effect relationship between the inhibition of tail thrombosis in mice and the rhizome of C. phaeocaulis both before and after the vinegar processing,were established to explore the functional changes of blood circulation and stasis after vinegar process. Based on the peak area from the fingerprint of UFLC-Q-TOF-MS of the alcohol extracts from the raw and vinegar-processed rhizome of C. phaeocaulis and their efficacy for inhibiting tail thrombosis,the correlation between the chromatography of UFLC-Q-TOF-MS and the inhibition of tail thrombosis in mice were analyzed by orthogonal partial least squares discriminant analysis( OPLS-DA) method. The results,produced by Simca-P software,showed that effective components consisted of eight peaks 16,24( aromadendrene oxide),3,11,22( dehydro-α-curcumene),19[( R)-(-)-α-curcumene],23 and 10 from the fingerprint,making great contribution to distinguish C. phaeocaulis raw products and the corresponding vinegar processed products. Therefore,from the perspective of inhibiting the formation of tail thrombosis in mice,the marker components could be found through the spectrum-effect relationship to distinguish C.phaeocaulis raw and vinegar products. This study provided new basis to explain the difference between the raw and the processed products of traditional Chinese medicine in the functional change of promoting blood circulation and removing blood stasis.

Anti-hepatic Fibrosis Mechanism of Cordyceps Polysaccharide / 中国实验方剂学杂志

Hepatic fibrosis is a repair process of the liver in response to various chronic injuries. The unbalanced proliferation and decomposition of fibrous tissue in the liver causes the excessive deposition of fibrous connective tissue in the liver. Hepatic fibrosis is a common intermediate link in a variety of chronic liver diseases. In this pathological process, the interaction between cells and cytokines leads to the disorder of liver extracellular matrix metabolism, which results in excessive deposition of fibrous tissue in the liver, and eventually causes liver fibrosis. After continuous deterioration, it would gradually develop into liver cirrhosis and even liver cancer. Because liver fibrosis and liver cirrhosis can be reversed in the early stage, it is very important to control the reversible process of liver fibrosis for the prevention and treatment of liver cirrhosis and liver cancer. Cordyceps, as one of valuable medicinal fungi in China, has been given widespread attention from scientific workers, with broad pharmacological actions. Cordyceps polysaccharide is the highest content of bioactive substances in Cordyceps. Recent studies have found that it has an anti-hepatic fibrosis effect. With the application of molecular biology technology, researches on the anti-liver fibrosis mechanism of traditional Chinese medicine at home and abroad have been gradually deepened into the cellular and molecular levels. This paper will investigate the preventive effect of Cordyceps polysaccharide in terms of cell basis, cytokines, collagenase and lipid peroxidation level that are related to liver fibrosis, so as to clarify the specific action mechanism on anti-hepatic fibrosis, and provide a reference for the development of anti-hepatic fibrosis drugs.

Recent advances of phage display techniques for drug discovery / 药学学报

Phage display technology utilizes filamentous phage display proteins and polypeptides to extract a desired polypeptide or protein from a large number of variants. The antibody fragments screened and obtained by phage display library technology play an important role in disease diagnosis and treatment. This article briefly introduces the principles of phage display technology, summarizes the development of monoclonal antibodies, the development of antigenic microbial vaccines, and the application of peptide drugs. This review highlights the importance of phage display technology in the diagnosis and treatment of various human diseases such as cancer and autoimmune diseases etc.

1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome promoting regulatory T cell-mediated resolution of inflammation

Vitamin D has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D [1,25(OH)D], the biologically active form of vitamin D, significantly attenuated monosodium glutamate (MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)D not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)D on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)D serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.

Preparation of a poIy(3-hydroxybutyrate-4-hydroxybutyrate)/poIyvinyI aIcohoI composite scaffoId by coaxiaI eIectrospinning and its biocompatibiIity / 中国组织工程研究

BACKGROUND: Poly(3-hydroxybutyrate-4-hydroxybutyrate) (P3HB4HB) is a kind of polymer material that can be completely degraded, has good film-forming property and physical properties, but has poor hydrophilicity. OBJECTIVE: To prepare P3HB4HB/polyvinyl alcohol (PVA) coaxial electrospun scaffolds, and to investigate the physical properties and biocompatibility of scaffolds in vitro. METHODS: We prepared P3HB4HB electrospun scaffold, PVA electrospun scaffold and P3HB4HB/PVA coaxial electrospun composite scaffold, and then detected the morphology and characterization, contact angle, and tensile mechanical properties of the scaffolds. Passage 4 bone marrow mesenchymal stem cells (BMSCs) from Sprague-Dawley rats were seeded on the three kinds of scaffolds. Cell adhesion rate was detected at 1, 3, 6 hours after seeding; cell proliferation was detect at 1, 3, 5, 7 days after seeding; and cell viability was observed fluorescence staining at 7 days after seeding. Passage 4 BMSCs were seeded onto the three kinds of scaffolds followed by 14 days of osteogenic and chondrogenic induction. Then, alizarin red staining and toluidine blue staining were used to verify BMSCs differentiation potentials. RESULTS AND CONCLUSION: (1) Scaffold morphology: Under the scanning electron microscope, the structure of the scaffold in each group was a three-dimensional interconnected network. The fiber diameters of P3HB4HB electrospun scaffold and P3HB4HB/PVA electrospun scaffold were homogeneous and ordered. The P3HB4HB/PVA scaffold showed an obvious core-shell structure under the transmission electron microscope. (2) Scaffold characterization: The tensile strength, tensile modulus and maximum stress of the P3HB4HB and P3HB4HB/PVA scaffolds were significantly higher than those of the PVA electrospun scaffold (P < 0.05). The contact angle of the P3HB4HB/PVA composite scaffold was less than 90°. (3) Cell adhesion rate was ranked as follows: PVA electrospun scaffold group >P3HB4HB/PVA composite scaffold group > P3HB4HB electrospun scaffold group (P < 0.05). (4) Proliferation and activity of cells: The cell proliferation of the P3HB4HB/PVA composite scaffold group was faster than that of the other two groups at 5 and 7 days (P < 0.05). There were more viable cells on the PVA electrospun scaffold and composite scaffold than on the P3HB4HB electrospun scaffold. (5) Cell differentiation: Osteogenesis and cartilage specific staining of the composite scaffold were stronger than those in the other two groups. Overall, the P3HB4HB/PVA coaxial electrospun scaffold has good biocompatibility and a certain mechanical strength.

Recent advances in monoclonal antibody-based therapeutics / 药学学报

Over the past four decades, monoclonal antibodies (MAbs) have evolved from bioscience research tools to powerful biopharmaceutical MAbs products for multiple diseases treatment. More than 50 therapeutic MAbs have been approved by FDA, widely used in cancer, autoimmune diseases and other diseases in current market. This article reviews the current progress of MAbs development technology, key molecules for cancer-targeted therapy and immunotherapy, and emphasizes the importance of MAbs for disease diagnosis and treatment.

Evaluation on curative effect of Stoppa approach combined with iliac fossa approach in treatment of patients with coxafossa anterior column or coxafossa dual column bone fracture / 吉林大学学报(医学版)

Objective:To investigate the curative effect and safety of Stoppa approach combined with iliac fossa approach in the treatment of the patients with coxafossa anterior column or coxafossa dual column bone fracture, and to provide a scientific evidence for its application in the treatment of the patients with coxafossa anterior column or coxafossa dual column bone fracture.Methods:Sixty-three patients with coxafossa anterior column or coxafossa dual column bone fracture were selected;among them 32 cases were treated with stoppa approach combined iliac fossa approach(Stoppa group),and 31 patients were treated with ilioinguinal approach(control group).The intraoperative blood loss volume,the operaton time,the reset quality of fracture and hip joint function after operation of the patients in two groups were evaluated.Results:The intraoperative blood loss volume of the patients in Stoppa group was lower than that in control group, and the difference was statistically significant (P<0.05).The operation time of the patients in Stoppa group was shorter than that in control group, and the difference was statistically significant (P<0.05).The reset quality of fracture of the patients in stoppa group was higher than that in control group, and the difference was statistically significant (P<0.05).The hip joint function of the patients in Stoppa group was higher than that in control group, and the difference was statistically significant (P<0.05).Conclusion:Stoppa approach combined with iliac fossa approach is an effective method in the treatment of the patients with coxafossa anterior column or coxafossa dual column bone fracture with sufficient exposure and tiny tissue damage.Stoppa approach combined with iliac fossa approach in the treatment of the patients with coxafossa anterior column or coxafossa dual column bone fracture has the advantages of shorter operative time,less blood loss, higher rate of anatomic reduction,and good joint function.

Effects of Atractylodis Macrocephale Rhizoma processed by different methods on salivary amylase and D-xylose excretion rate in rats / 中国中药杂志

To observe the effects of Atractylodis Macrocephale Rhizoma processed by different methods (sulfur-fumigation, different temperatures baking and microwave sterilization) on salivary amylase and D-xylose excretion rate in spleen deficiency rats. The rats were divided into blank control group, rhubarb-induced spleen deficiency model control group, and Atractylodis Macrocephale Rhizoma experimental groups processed with different methods. Amylase colorimetric method was used to determine the activities of salivary amylase and D-xylose excretion rate was measured with O-benzylamine method. Then the correlation of salivary amylase activity and D-xylose excretion rate in urinary was analyzed. As compared with blank control group, Atractylodis Macrocephale Rhizoma baked at 100,110 ℃ can increase the unit content of rat salivary amylase and D-xylose excretion rate, with a significant difference (P<0.05). As compared with the model group, Atractylodis Macrocephale Rhizoma baked at 70 ℃ and Atractylodis Macrocephale Rhizoma with microwave treatment had stronger effects than the others, with statistically significant differences (P<0.01). Atractylodis Macrocephale Rhizoma could improve D-xylose absorption function and salivary amylase activity in spleen deficiency rats. In addition, D-xylose excretion rate in urine was positively correlated with salivary amylase activity. Atractylodis Macrocephale Rhizoma processed with different temperatures baking and microwave sterilization had little impact on salivary amylase activity and D-xylose excretion rate in urine of spleen deficiency rats, while sulfur fumigation had great effects on the above two indexes.

Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, α-SMA, inflammatory cytokines, and transcription factors NF-κB, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.