Role and significance of artificial intelligence preoperative planning in total hip arthroplasty / 中国组织工程研究

BACKGROUND:The preoperative planning of traditional X-ray films is often inaccurate,which can lead to some intraoperative and postoperative complications,increase the operation time and intraoperative blood loss,and to some extent affect the surgical outcome of total hip arthroplasty. OBJECTIVE:To investigate the accuracy and effectiveness of artificial intelligence preoperative planning in total hip arthroplasty. METHODS:Sixty patients who underwent primary total hip arthroplasty on the affected side were selected.30 of them used artificial intelligence 3D preoperative planning(trial group)and 30 used conventional X-ray film 2D preoperative planning(control group),and there were no statistically significant differences between the two groups in terms of gender,age,condition and other general data(P>0.05).The actual intraoperative prosthesis placement and preoperative planning prosthesis matching,intraoperative operation time,intraoperative blood loss,bilateral femoral eccentric distance difference,bilateral joint eccentric distance difference and bilateral lower limb length difference,and Harris score at 3 months after operation were compared between the two groups,and the accuracy and application effect of the two preoperative plans were analyzed. RESULTS AND CONCLUSION:(1)Patients in both groups were followed up for 4-6 months postoperatively.One patient in the control group had a posterior dislocation of the prosthesis at 5 days postoperatively,which recovered after performing manual repositioning without re-dislodgement.The rest of the patients did not have postoperative complications or postoperative death.(2)Complete matching rate of the prosthesis on the acetabular side and femoral side was significantly better in the trial group than that in the control group(P<0.05).(3)Operation time and intraoperative blood loss were significantly less in the trial group than those in the control group(P<0.05).(4)The difference in bilateral lower limb length between the two groups was statistically significant(P<0.05),and the difference in bilateral femoral eccentric distance and bilateral joint eccentric distance was not statistically significant(P>0.05).(5)Harris score of patients in the trial group was significantly higher than that in the control group 3 months after operation(P<0.05).(6)These results confirm that compared with traditional film planning,artificial intelligence preoperative planning can predict the prosthesis type more accurately,shorten the operation time,reduce intraoperative blood loss,diminish the occurrence of postoperative bilateral lower limb inequality,and accelerate postoperative recovery.

Research progress on the pathogenesis and treatment of gallbladder cancer / 中国现代普通外科进展

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Protective effects of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes / 中成药

AIM To investigate the protective effects and the mechanism of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes.METHODS To screen and determine the effective concentration of corosolic acid,the injury models of H9c2 cardiomyocytes established by 1 μmol/L doxorubicin were exposed to 24 h different concentrations of corosolic acid,followed by detections of their cell activity by MTT method;their cell apoptosis morphology by Hoechst 33342 staining method;their cell apoptosis rate by Annexin V-FITC/PI double staining method;their intracellular ROS level by DCFH-DA probe;their intracellular iron level by iron ion colorimetry;and their protein expressions of Bax,Bcl-2,cleaved-caspase3,Nrf2,GPX4 and Ptgs2 by Western blot.RESULTS Upon the doxorubicin-induced injury models of H9c2 cardiomyocytes,corosolic acid improved their viability and survival rate(P<0.05),decreased their levels of ROS and Fe2+ and the apoptosis rate(P<0.05),up-regulated the protein expressions of Bcl-2,Nrf2 and GPX4(P<0.05),and down-regulated the protein expressions of Bax,cleved-caspase 3 and Ptgs2(P<0.05).CONCLUSION Corosolic acid can inhibit the ROS level and apoptosis of doxorubicin-induced injury models of H9c2 cardiomyocytes,and the iron death as well via activating Nrf2/GPX4 pathway.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke.

p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynamic regulation of the acetylation of p53 at lysine 320 is controlled by acetyltransferase PCAF and histone deacetylases HDAC1 and HDAC6. The in silico simulation have made it possible to suggest the acetylation of p53 at lysine 320 acetylation may facilitate the shuttling of p53 between the nucleus and cytoplasm in penumbra neurons. Acetylation of p53 at lysine 320 is more preferable than acetylation at lysine 373 and probably promotes survival and repair of penumbra neurons after stroke. Strategies to increase p53 acetylation at lysine 320 via increasing PCAF activity, inhibiting HDAC1 or HDAC6, inhibiting p53, or a combination of these interventions may have therapeutic benefits for stroke recovery and would be promising for neuroprotective therapy of stroke.

The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

Carotid endarterectomy for symptomatic carotid artery near-occlusion / 中华普通外科杂志

Objective:To investigate the effect of carotid endarterectomy(CEA) in the treatment of symptomatic carotid artery near-occlusion(CNO).Methods:Clinical symptoms, imaging examination, treatment and prognosis of 122 symptomatic CNO patients admitted to China-Japan Friendship Hospital from Jan 2014 to Jan 2020 undergoing CEA were retrospectively analyzed. Patients were divided into two groups based on the collapse condition,full collapse group(54 cases) and non-full collapse group(68 cases).Results:The difference was insignificant between the two groups at the 30-day and 12-month occurrence rate of primary endpoints(1.85% vs. 4.41%, P=0.629;7.41% vs. 4.41%, P=0.698).Postoperative re-stenosis occurred in one case in the non-full collapse group 8 months after CEA. Conclusions:CEA can achieve good curative effect for patients with CNO with recurrent symptoms, irrelevant to the existence of distal full collapse. The shunt can prevent intraoperative hypoperfusion and postoperative hyperperfusion.

Paclitaxel drug-coated balloons combined with bare metal stents vs. bare metal stents for the treatment of superficial femoral atherosclerosis obliterans / 中华普通外科杂志

Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.

Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the common malignant tumors with high morbidity， and changes in lifestyle， dietary structure and environment in China in recent decades have been associated with an increase in the incidence of colorectal cancer. A large number of studies have shown that traditional Chinese medicine（TCM） can be used as a complementary and alternative treatment for colorectal cancer after conventional western medicine treatment. TCM physicians have accumulated a lot of clinical experience in the treatment of patients with stage Ⅰ-Ⅲ colorectal cancer， and have proved that TCM has unique efficacy， but there is still a lack of relevant clinical practice guidelines to standardize and guide the diagnosis and treatment of TCM. Based on this， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， under the framework of relevant laws， regulations and technical guidance documents， combined with the evidence of relevant domestic and foreign clinical research in recent years for evidence grading and opinion recommendation， and then the Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer were developed by expert consensus. This guideline introduces the etiology， pathogenesis， syndrome differentiation and treatment of TCM intervention for colorectal cancer， which can provide guiding opinions for TCM clinicians and clinicians of integrated traditional Chinese and western medicine engaged in the prevention and treatment of colorectal cancer.

Molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacology and molecular docking / 国际生物医学工程杂志

Objective:To explore the molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacological analysis and molecular docking.Methods:Taking matrine as the object, the corresponding potential drug targets in matrine were obtained from Swiss Target Prediction database, and SuperPred database, and the database of traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Differential genes were obtained from gene expression omnibus (GEO), and GeneCards, OMIM, DrugBank, and CTD databases were used to collect colorectal cancer-related genes. Furthermore, core targets were screened by establishing protein-protein interaction (PPI) networks. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed by bioconductor of R language. Finally, the molecular docking calculation was performed to evaluate the interaction between matrine and core targets.Results:Matrine contained 63 targets. A total of 14 198 targets for colorectal cancer were obtained. The topology analysis results of the PPI network showed that 5 main targets such as myelocytomatosis proteins (MYC), interleukin-6 (IL-6), Caspase-3 (CASP3), mammalian target of rapamycin (mTOR), and amphiregulin (AR). GO enrichment analysis found that biological process (BP) mainly includes hydrogen peroxide reaction, cell reaction to hydrogen peroxide and cell response to chemical stress, etc; Cell components (CC) mainly include lipid rafts, membrane microregions and synaptic membranes, etc; Molecular functions (MF) mainly include transcriptional coregulatory factor binding, postsynaptic neurotransmitter receptor activity and core promoter sequence-specific DNA binding. KEGG pathway analysis showed that it involved chemical carcinogenesis-receptor activation, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway, etc. Molecular docking showed that matrine had good binding with the core target.Conclusions:Matrine acts on targets such as MYC, IL-6, CASP3, mTOR, and AR, and exerts therapeutic effects on colorectal cancer by regulating chemical carcinogenesis-receptor activation, TNF signaling pathway, Toll-like receptor signaling, etc.

Effects of Liujun Anwei Prescription on NF-κB and iNOS protein in small intestine of mice with chemotherapy-related diarrhea based on mass spectrometry and network pharmacology / 国际中医中药杂志

Objective:To investigate the potential key targets of Liujun Anwei Prescription and its effects on NF-κB/iNOS-NO in small intestine of mice with chemotherapy- associated diarrhea; To reveal the anti-inflammatory components and molecular mechanism.Methods:UPLC-Q/TOF MS combined with UNIFI software was used to analyze the chemical components of Liujun Anwei Prescription. PubChem database was searched to obtain the active components of Liujun Anwei Prescription, and the Swiss Target Prediction was used to predict the targets. The database of DisGeNET, OMIM and GeneCards were searched to obtain the targets of chemotherapy-related diarrhea. The potential targets of Liujun Anwei Prescription in the treatment of chemotherapy-related diarrhea diseases were obtained by crossing the targets of active components of Liujun Anwei Prescription and those related to diarrhea diseases. The PPI network and component-target-pathway network were constructed by Cytoscape 3.7.1 software, and the intersecting targets were analyzed by GO and KEGG based on David Database. The potential active components and potential targets predicted in the network were verified by using Autodock software. 60 C57BL/6J male mice were divided into normal control group, model group, positive control group and Liujun Anwei Prescription high-, medium- and low-dosage groups according to random number table method, with 10 mice in each group. In addition to the normal control group, the other groups of mice were intraperitoneally injected with 5-fluorouracil injection 50 mg/kg preparation to construct CID mouse model. After 14 days, the expressions of NF-κB and iNOS in jejunum were detected by Western blot.Results:A total of 197 compounds were identified, and 156 key compounds of Liujun Anwei Prescription were screened, involving 82 potential targets, mainly through NOS2 and other key targets, playing a role through cancer pathway, PI3K-Akt, NF-κB signal pathway. The experimental results showed that Liujun Anwei Prescription could significantly down-regulate the protein expressions of NF-κB and iNOS.Conclusion:This study reveals the pharmacodynamic material basis of Liujun Anwei Prescription, which can be achieved by decreaseing the levels of NF-κB and iNOS to affect the inflammatory response of intestinal tissue, improve intestinal mucosal barrier function, and thus improve chemotherapy related diarrhea.

Discussion on Mechanism of Danggui Buxue Decoction in treatment of chemotherapy-induced myelosuppression based on network pharmaccology and molecular docking / 国际中医中药杂志

Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.

Exploration and application of online teaching in first aid skill operation course / 中华医学教育探索杂志

Objective:To explore the teaching effect and novel ideas of online teaching applied in skill operation course.Methods:One hundred and fifty-one students studying in Sichuan University taking the First Aid in the Life: Basic Knowledge and Skills as an elective course in the autumn semester of 2019 and spring semester of 2020 were included as the research subjects in this study. Among them, 77 students in the spring semester of 2020 were selected as the experimental group and 74 students in the autumn semester of 2019 were selected as the control group. The students in the experimental group studied the first aid course by online platform, and the others in the control group studied through traditional teaching mode. The teaching effect of the two groups was compared and the teaching satisfaction of the two groups weas analyzed. SPSS 23.0 was used for Chi-square test and t-test. Results:There was no significant difference between the control group and the experimental group in the assessment scores of cardiopulmonary resuscitation, hemostatic bandaging, and fracture fixation [(8.65±0.81 vs 8.69±0.90, P=0.750); (8.10±0.50 vs 8.12±0.61, P=0.880); (8.21±0.89 vs 8.16±0.78, P=0.710)]. Among the students participating in the questionnaire survey in the experimental group, 59 (95.16%) students thought that this course was helpful in dealing with first aid in daily life, and 38 (61.29%) students did not want to change the traditional teaching method to online teaching. Conclusion:The application of online teaching in first-aid skill operation course is feasible and can achieve the similar teaching effect, which provides a novel idea for exploring the online teaching of first aid skills.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Sinomenine inhibits oxidative stress and pulmonary fibrosis by activating the Keap1/Nrf2 signaling pathway / 中国临床药理学与治疗学

AIM: To explore the protective effects of sinomenine (SIN) on oxidative stress and pulmonary fibrosis and its relationship with the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. METHODS: MRC-5 cells were treated with hydrogen peroxide (H2O2) to establish the oxidative stress injury model, followed by administration with SIN. Cell viability was detected using the CCK-8 method. The biochemical kits were employed to measure malondialdehyde (MDA) content and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. The protein expression of Keap1 and Nrf2 was examined by western blot. Thirty SD rats were randomly divided into control group, bleomycin A5 (BLM) group and BLM + SIN group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to the rats in BLM group and BLM+SIN group to establish the pulmonary fibrosis model. The rats in control group received the same volume of 9 g/L sodium chloride solution. The second day after model construction, the rats in BLM+SIN group were gavaged with SIN, while the rats in the other two groups were treated with 9 g/L sodium chloride solution. On day 28, all rats were sacrificed. Pulmonary tissue was isolated, and HE and Masson staining was performed to observe the pathological changes. The MDA content and SOD, GSH-Px and CAT activities in pulmonary tissue were evaluated. Western blot was used to assay pulmonary tissues Keap1 and Nrf2 protein expression. RESULTS: When compared with H2O2 group, SIN treatment increased cell viability, decreased MDA content, elevated SOD, GSH-Px and CAT activities, down-regulated Keap1 expression, and promoted nuclear translocation of Nrf2 in MRC-5 cells. In comparison with BLM group, administration of SIN decreased alveolitis and pulmonary fibrosis pathological changes and scores as well as pulmonary tissue MDA content, enhanced pulmonary tissues SOD, GSH-Px and CAT activities, down-regulated pulmonary tissues Keap1 expression, and raised Nrf2 levels in the nucleus. CONCLUSION: SIN alleviates oxidative stress and pulmonary fibrosis possibly by activating the Keap1/Nrf2 signaling pathway.

Selection and validation of reference genes for quantitative real-time PCR analysis in Paeonia veitchii / 中国中药杂志

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.

Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Comparison of 5-year follow-up outcomes between"one-stop"procedure and long-term oral anticoagulants after radiofrequency catheter ablation in patients with atrial fibrillation / 中华心血管病杂志

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ2=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.

Comparison of 5-year follow-up outcomes between"one-stop"procedure and long-term oral anticoagulants after radiofrequency catheter ablation in patients with atrial fibrillation / 中华心血管病杂志

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ2=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.