Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

OBJECTIVE To systematically evaluate the efficacy and safety of compound danshen preparations combined with conventional chemical drug treatment for peptic ulcer （PU）， providing evidence-based guidance for clinical treatment of PU. METHODS Related clinical randomized controlled trials were collected from CNKI， VIP， Wangfang data， CBM， PubMed， Embase and Web of Science from their establishment date to September 30， 2023. The qualities of included literature were evaluated by Cochrane Systematically Evaluator Manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were conducted with RevMan 5.3 software. RESULTS Totally 26 pieces of literature were included with total of 2 451 cases， including 1 243 cases in trial group （compound danshen preparations+conventional chemical drug treatment） and 1 208 cases in the control group （conventional chemical drug treatment）. In terms of effectiveness， trial group had significant advantages in ulcer healing rate [OR＝4.66， 95%CI （3.53， 6.15）， P＜0.000 01]， HP eradication rate [OR＝1.90， 95%CI （1.12， 3.22）， P＝0.02]，and pain relief rate [OR＝3.91， 95%CI （2.31， 6.61）， P＜0.000 01] than control group， while ulcer recurrence rate [OR＝0.22， 95%CI （0.15， 0.32）， P＜0.000 01] and serum levels of pepsinogen （PG）Ⅰ [SMD＝－1.92， 95%CI （－2.25， －1.58）， P＜0.000 01]， PGⅡ [SMD＝－3.88， 95%CI （－4.35， －3.41）， P＜0.000 01] and G-17 [SMD＝－3.44， 95%CI （－3.87， －3.00）， P＜0.000 01] were significantly lower than control group. In terms of safety， the main adverse reactions were abdominal discomfort， headache， dizziness， dry mouth， facial flushing， etc. There was no significant difference in the incidence of adverse reactionsbetween the two groups [OR＝1.08， 95%CI （0.75， 1.54）， P＝0.69]. Subgroup analysis of ulcer healing rate and HP eradication rate based on dosage form showed that HP eradication rate in the compound danshen pellet group was not significantly improved compared to the control group， with consistent results for the remaining outcomes. The sensitivity analysis showed that above results were stable. There was less possibility of publication bias in this study. CONCLUSIONS Compared with conventional chemical drug treatment alone， the combination of compound danshen preparations can effectively improve the clinical symptoms of PU patients with similar safety.

Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P＜0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P＜0.01)and the level of ROS(F=52.99,P＜0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P＜0.05),p-PKCα(F=24.56,P＜0.05)and HIF-1α proteins(F=6.85,P＜0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Objective To study and compare the oral microbiota and metabolites of children with Henoch Schonlein purpura(HSP)to identify specific microbiota and metabolites related to this disease and elucidate the pathogenesis of HSP.Methods Three groups of qualified subjects were included,including 20 in the HSP group,20 in the HSP nephritis(HSPN)group,and 20 in the control group.Perform high-throughput 16S rRNA sequencing and metabolic profiling of saliva from each group to analyze the correlation between differential microbiota and differ-ential metabolites.Results(1)Compared with the control group,there was a significant difference in richness and diversity in the HSPN group(P＜0.05).At the same time,there was no significant difference in richness and diver-sity in the HSP group(P＞0.05).Compared with the HSP group,the abundance,and diversity of the HSPN group were significantly increased(P＜0.05).At the genus level,the proportion of Streptococcus in each group is the high-est.Compared with the control group,there was no significant correlation between the HSP group and the genus of bacteria.In contrast,the HSPN group showed a significant increase in the genera of Pseudomonas and Parabacteroi-des(P＜0.05).Compared with the HSP group,the abundance of Pseudomonas and Parabacteroides in the HSPN group was significantly increased(P＜0.05).(2)Compared with the control group,the HSPN group had 12 differen-tial metabolites involving nine metabolic pathways,such as phenylalanine metabolism;There was no significant dif-ference in metabolites and no metabolic pathway in the HSP group.Compared with the HSP group,the HSPN group has 15 differential metabolites involving nine metabolic pathways,such as phenylalanine metabolism.(3)In the HSPN and control groups,Pseudomonas and Parabacteroides negatively correlated with Phenylalanine metabolic pathway products.In the HSPN and HSP groups,Pseudomonas,Parabacteroides,and Phenylalanine metabolic path-way products were negatively correlated.The metabolites involved in phenylalanine metabolism in the oral cavity are 2-hydroxycinnamic acid,Phenylpyruvic acid,and N-acetyl-L-phenylalanine.Conclusion There is a significant dif-ference between HSPN and HSP children and healthy children.Streptococcus,Pseudomonas,and Parabacteroides may be one of the trigger factors of HSPN,and Phenylalanine metabolism may be one of the pathways in the patho-genesis of HSPN.Children with HSPN have a more pronounced imbalance in oral microbiota and greater differences in metabolic products than children with HSP.

Objective To explore the dynamic changes in cerebral hemodynamics in patients with unilateral middle cerebral artery(MCA)occlusion after superficial temporal artery(STA)-MCA bypass surgery.Methods One hundred and nine patients diagnosed with unilateral MCA occlusion by DSA who underwent STA-MCA bypass surgery were retrospectively included in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University.Clinical data of patients were collected within 24 hours after admission,including age,sex,body mass index,stroke risk factors including hypertension,hyperlipidemia,diabetes,smoking,drinking history and atrial fibrillation,clinical manifestations(within the last 6 months;nonspecific symptoms[dizziness,memory loss,unresponsiveness,etc.],transient ischemic attack,and stroke),blood biochemical markers(low density lipoprotein cholesterol,high density lipoprotein cholesterol,triglyceride,total cholesterol,fasting blood glucose,and hypersensitive C-reactive protein),and National Institutes of Health stroke scale(NIHSS)score at admission.Color Doppler ultrasound(CDU)and transcranial color coded Doppler(TCCD)ultrasound were used to evaluate the hemodynamic parameters of STA before and at different periods after surgery(4-7 days and 1,3,6,12 months after surgery)to analyze the patency of bypass arteries and intracranial hemodynamic changes,and to check the consistency of the results of the bridge artery patency at 12 months postoperatively by CDU and DSA,consistency test was performed.According to the results of the DSA examination 12months after surgery,the patients were divided into the bypass artery patency group and the non-patency group(stenosis or occlusion).The hemodynamic parameters at the trunk of STA,namely the extracranial segment,transcranial,and intracranial part of the bypass arteries,were compared between the two groups.It included inner diameter(D),peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),pulsation index(PI),time-averaged mean velocity(TAMV),time-averaged peak velocity(TAPV),and calculated flow of the STA trunk including TAMV flow and TAPV flow.Head CT,CT angiography(CTA)above the aortic arch,and CT perfusion(CTP)of the whole brain were performed 1 to 3 days before surgery and 12 and 18 months after surgery to observe the changes in cerebral perfusion.Head CT was performed 1 to 2 days after the operation to observe whether there were new hemorrhagic and ischemic lesions in the operative area.the CTP parameters of the two groups were compared including 12 and 18 months after the operation with 1 to 3 days before the surgery,and the differences in CTP parameters between the two groups were compared.The modified Rankin scale(mRS)was used to evaluate the neurological function prognosis of the patients at 12 and 18 months after surgery.The mRS score 2 was divided into a good prognosis and mRS score≥3 was a poor prognosis.NIHSS score of the patients was recorded 7 days,12,and 18 months after surgery.Results(1)Consistency analysis of CDU and DSA:the consistency of the assessment of bypass artery patency was excellent at 12 months after surgery,and the Kappa value was 0.94(95％CI 0.81-1.00,P＜0.01).According to DSA,101 cases(92.7％)were in bypass artery patency group,while 8 cases(7.3％)in the non-patency group(no case of occluded bridge vessel was found),and the sites of stenosis in the bypass arteries were all located in the transcranial segment.(2)Hemodynamic parameters:compared with the preoperative results,the D of the extracranial segment increased on 4-7 days and 1,3,6,and 12 months after the operation(Wald x2=30.438).Hemodynamic parameters included increased blood velocity such as PSV,EDV,TAMV,and TAPV(Waldx2 was 12.117,29.310,31.075 and 17.525,respectively)and blood flow including TAMV flow and TAPV flow(Wald x2 was 54.503 and 34.986,respectively)increased,while RI and PI values were decreased(Waldx2 was 112.568 and 103.629,respectively),and the differences were statistically significant(all P＜0.05).However,there was no significant difference in hemodynamic parameters in the non-patency group at 12 months after operation(all P＞0.05).Compared with 4-7 days after surgery,PSV(252.0[206.8,315.3]cm/s vs.102.5[84.0,119.0]cm/s)and EDV(119.5[106.3,159.8]cm/s vs.43.5[36.8,52.0]cm/s)in the non-patency group were significantly higher at the cranial entrance 12 months after surgery(both P＜0.05),but there was no significant difference in RI and PI values(both P＞0.05).Compared with 4-7 days after surgery,the blood flow parameters of STA intracranial segment,including PSV(29.4[24.8,41.4]cm/s vs.111.5[63.3,120.0]cm/s),EDV(19.7[15.2,22.2]cm/s vs.58.5[28.3,70.0]cm/s)and PI(0.55[0.42,0.63]vs.0.83[0.61,0.90])values in the non-patency group at 12 months after surgery were significantly decreased(all P＜0.05).(3)CTP parameters:the relative cerebral blood flow(rCBF)of the patency group increased at 12 and 18 months after surgery compared to preoperative levels,while relative cerebral blood volume(rCBV),relative peak time(rTTP)and relative mean transit time(rMTT)decreased,with statistical significance(all P＜0.05).At 12 and 18 months after operation,rCBF increased,while rMTT decreased in the non-patency group(both P＜0.05),but there was no significant difference as for rCBV and rTTP.The rTTP of the patency group at 12 and 1 8 months was lower than that of the non-patency group(12 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.024;1 8 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.023),but there was no statistical significance for other parameters between the two groups(all P＞0.05).(4)NIHSS score and prognosis:clinical follow-up results 18 months after the operation showed that no new stroke occurred during the follow-up period.The NIHSS scores in the patency group and the non-patency group were remarkably lower at 7 days,12,and 18 months after surgery than at admission(patency group:2[0,4],1[0,2],0[0,2]vs.3[0,6],respectively;the non-patency group:3[1,5],3[1,6],2[1,6]vs.4[1,7],respectively),with significant differences(all P＜0.05);However,the NIHSS scores in the patency group were significantly lower than that in the non-patency group at 12 and 18 months after surgery,and the proportion of patients with good prognosis in the patency group was substantially higher than that in the non-patency group(12months:87.1％[88/101]vs.4/8,P=0.039;18 months:90.1％[91/101]vs.4/8,P=0.025).Conclusion CDU can quantitatively evaluate the hemodynamic changes of bypass arteries after the STA-MCA bypass procedure,which can be applied to the long-term dynamic follow-up after the surgery.

Objective To develop an evidence-based practice program for ICU eye care and evaluate its application effect using Stetler model of research utilization.Methods The systematic search was carried out in domestic and foreign guid elines,systematic reviews,evidence summaries,expert consensuses on eye care for ICU patients.The quality of the included literature was evaluated and the evidence was summarized.The evidence based on expert advice,clinical context and stakeholder opinions was screened.According to Stetler model of research utilization,the evidence translation/application was formulated from 3 aspects,including method,level and type of evidence application,and the evidence translation was implemented using a stepwise trial design.Five ICUs in a tertiary hospital in Zhejiang Province were selected,and the order of enrollment of each ICU was determined by computer-generated random numbers from April to september,2022.In the first month,all ICUs were in pre-evidence-based practice period,and in the second month,an ICU was trained and entered the evidence-based practice period.Until the 6th month,all ICUs entered the evidence-based practice period.Then the rate of ocular symptoms and implementation rate of eye care measures were compared before and after EBP.Results A total of 1 540 patients were included.With regard to the implementation rate of eye care measures,the rate of lubricant use and suspected ocular infection management in patients at high risk for ocular complications in evidence-based practice period was significantly higher compared with pre-evidence-based practice period(P＜0.001),and no statistically significant difference was found in the rate of eyelid closure.The incidence of conjunctival exposure,subconjunctival hemorrhage,conjunctival congestion,and ocular discharge in non-neurology critical care patients decreased compared with pre-evidence-based practice period(P＜0.05),and the incidence of conjunctival edema and conjunctival congestion in NICU patients decreased compared with pre-evidence-based practice period as the intervention continued(P＜0.001).Conclusion Evidence-based practice in eye care for ICU patients using Stetler model of research utilization can standardize the practice of eye care for ICU patients and improve the quality of care.

In this study,we aim to provide a comprehensive overview of the postoperative nursing care for patients undergoing radiofrequency catheter ablation in conjunction with minimally invasive left ventricular assist device implantation.The main nursing considerations include the following aspects.Regular assessment of the pulsation of bilateral lower limb arteries was conducted in order to maintain vigilance against the occurrence of deep vein thrombosis;the goal-oriented fluid management strategies were executed;it was crucial to focus on gastrointestinal responses and take steps to prevent gastrointestinal bleeding;the monitoring of chest indicators and respiratory function was enhanced to facilitate early detection of pneumothorax;the optimization of pain management was maximized.Following meticulous care and medical attention,the patient was transferred to the general ward on the 8th day post-surgery.On the 21st day after the procedure,the patient achieved full recovery and was subsequently discharged.