Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

OBJECTIVE To investigate the effects of 0.2% chloroprocaine combined with ropivacaine on epidural labor analgesia and median effective concentration （EC50） of ropivacaine. METHODS Totally 67 parturients who scheduled for vaginal delivery and required epidural labor analgesia were collected from our hospital from July to October 2023 and randomly divided into RL group （33 cases） and R group （34 cases）. The concentration of ropivacaine was determined by modified Dixon sequential method. RL group was given 0.2% Chloroprocaine hydrochloride injection+Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection； R group was given Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection. EC50 of ropivacaine， analgesic effect during delivery， total dosage of analgesic drugs， analgesic satisfaction score， the incidence of adverse reactions， delivery status， and Apgar score of newborns were observed in two groups. RESULTS EC50 of ropivacaine， onset time， remedial analgesia rate， the incidence of perineal distension and breakthrough pain and total dosage of analgesic drugs of RL group were significantly lower than R group， and analgesic satisfaction score was significantly higher than R group （P＜0.05）. There was no statistical significance in the incidence of adverse reactions such as numbness， weakness， and chills in the lower limbs， or the duration of labor， amount of bleeding， mode of delivery， and Apgar score of newborns between 2 groups （P＞0.05）. CONCLUSIONS For epidural labor analgesia， 0.2% chloroprocaine combined with ropivacaine can reduce EC50 of ropivacaine， improve analgesia effect and have good safety.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Objective The study aims to investigate the effects of different adaptive statistical iterative reconstruction-V（ ASiR-V） and convolution kernel parameters on stability of CT auto-segmentation which is based on deep learning. Method Twenty patients who have received pelvic radiotherapy were selected and different reconstruction parameters were used to establish CT images dataset. Then structures including three soft tissue organs (bladder, bowelbag, small intestine) and five bone organs (left and right femoral head, left and right femur, pelvic) were segmented automatically by deep learning neural network. Performance was evaluated by dice similarity coefficient（ DSC） and Hausdorff distance, using filter back projection(FBP) as the reference. Results Auto-segmentation of deep learning is greatly affected by ASIR-V, but less affected by convolution kernel, especially in soft tissues. Conclusion The stability of auto-segmentation is affected by parameter selection of reconstruction algorithm. In practical application, it is necessary to find a balance between image quality and segmentation quality, or improve segmentation network to enhance the stability of auto-segmentation.
Algorithms ; Humans ; Image Processing, Computer-Assisted ; Neural Networks, Computer ; Radiation Dosage ; Tomography, X-Ray Computed

Objective:To establish and validate a predictive model for treatment failure of peritoneal dialysis-related peritonitis(PDAP)in elderly patients.Methods:Clinical data of peritoneal dialysis(PD)patients who were followed up from January 1, 2013 to December 31, 2019 at four Grade A tertiary hospitals in Jilin Province were collected.A total of 362 elderly patients with PDAP were eventually included as study subjects.Subjects recruited from 2013 to 2017 were used for model construction and the logistic regression model was used to screen risk factors for treatment failure of PDAP in elderly patients.A nomogarm was constructed to predict treatment failure of secondary PDAP using R language.The receiver operating curve(ROC)and calibration curve were used to evaluate discrimination accuracy of the model.Subjects from 2018 to 2019 were used as the cohort for validation of discrimination accuracy of the model.Results:Of 258 PDAP patients in the modeling cohort, 29 experienced treatment failure, including 15 PDAP-related deaths and 14 cases requiring catheter removal.The multivariate logistic regression model showed that types of pathogens( OR=8.849, 95% CI: 1.656-47.269, P=0.011), long dialysis age( OR=1.023, 95% CI: 1.005-1.042, P=0.013), pre-hospitalization antibiotic treatment( OR=5.123, 95% CI: 1.338-19.610, P=0.017), and dialysate white blood cell count on day 5>100×10 6/L( OR=7.085, 95% CI: 2.162-23.217, P=0.001)were independent risk factors for treatment failure of PDAP in elderly patients.For the nomogarm predictive model, the areas under the ROC curve(AUC)in the modeling cohort and the validation cohort were 0.818(95% CI: 0.735-0.902)and 0.762(95% CI: 0.656-0.889), respectively, and the calibration curves were close to a straight line with a slope of 1. Conclusions:Our nomogram predictive model based on types of pathogens, months of dialysis, pre-hospital admission antibiotic treatment, and dialysate white blood cell count on day 5 has demonstrated satisfactory discrimination accuracy for treatment failure of PDAP in elderly patients.

Objective To analyze the characteristics of chronic hepatitis B (CHB) complicated with non-alcoholic fatty liver disease (NAFLD), and to provide countermeasures for the prevention of NAFLD. Methods A total of 348 patients with CHB admitted to our hospital from June 2018 to June 2021 were randomly selected and divided into experimental group (CHB combined with NAFLD, n=195) and control group (CHB, n=153) according to whether they had NAFLD or not. Basic data such as age, sex, BMI (kg/m²), history of diabetes, history of hypertension, and history of alcohol consumption were collected. Serum indexes such as liver function (AST, ALT, GGT, ALP, ALB), blood lipid (TG, ldl-c), fasting blood glucose (FBG) and virological indexes such as hepatitis B virus (HBV DNA) were collected. Results A total of 348 CHB patients were included in the study, including 195 (56.03%) patients with NAFLD. The high NAFLD incidence age was between 30 and 45 years old (163 cases, 46.84%). The incidence of NAFLD in male (131 cases, 70.81%) was significantly higher than that in female (64 cases, 39.26%) (χ²=35.005, P<0.05). The incidence of NAFLD in male patients was significantly higher than that in female patients at age <30 and 30~45 (χ²=10.625, χ²=20.238, P<0.05). There was no significant difference in the incidence rate of NAFLD between men and women at age >45 years (χ²=2.005, P>0.05). There were no significant differences in the history of hypertension, ALT and ALP between the two groups (P>0.05). The differences in age, sex, BMI, history of diabetes, history of alcohol consumption, AST, TG, TG, FBG and FBG between the two groups were statistically different (P<0.05). Logistic regression analysis showed that increased BMI, AST, FBG and LDL were independent risk factors for NAFLD in CHB patients (P<0.05). Conclusions CHB with NAFLD often has glucolipid metabolic disorder, which is related to increased body mass index and AST. It is suggested that we should strengthen the health management of patients with high blood pressure, diabetes, overweight, and obesity, guide patient to balance their diet, adjust their diet structure, control their body weight and glycolipid abnormalities, adjust body fat, reduce blood pressure by drugs, and control blood sugar in a timely manner, and maintain a healthy lifestyle.

Objective: To investigate the effect of secreted protien acidic and rich in cysteine(SPARC) gene on the proliferation and apoptosis of human keloid fibroblasts and its mechanismin vitro. Methods: The lentiviral vector carrying SPARC shRNA(LV2 N-shRNA-SPARC,sh-SPARC group)and empty plasmid(LV2-NC,sh-NC group)were transfected into human keloid fibroblasts(HKF) respectively. Real-time PCR(qRT-PCR) and Western blot were performed to examine the expression of SPARC mRNA and protein in HKF. MTT assay was used to estimate the cell proliferation. The cell cycle and apoptosis of HKF were detected by flow cytometry. The expression of TGF-β1 and TβRⅠ proteins in HKF were detected by Western blot. Results: (1) After transfection of SPARC shRNA lentiviral vector, the expression of SPARC mRNA and protein in HKF were significantly down-regulated compared with those in the control groups(P<0.05).(2) MTT assay showed that the proliferation of sh-SPARC groups decreased compared with the control groups(P<0.05).(3) Flow cytometry results showed that the S phase cell ratios of sh-SPARC groups were reduced while the apoptosis rates increased compared with the control groups(P<0.05).(4) Western blot showed that the protein expression levels of TGF-β1 and TβRⅠsignificantly decreased in shSPARC groups. Conclusion SPARC gene silencing inhibits the proliferation blocks cell cycle progression and promotes cell apoptosis in HKF, which may be related to the down-regulation of the TGF-β signaling pathway.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

Current advances of immunotherapy have greatly changed the way of cancer treatment. At the same time, a great number of nanoparticle-based cancer immunotherapies (NBCIs) have also been explored to elicit potent immune responses against tumors. However, few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of