Objective To investigate the effect of icotinib on right ventricular remodeling in rats with monocrotaline(MCT)-induced pulmonary hypertension(PH).Methods Sprague-Dawley rats were randomly divided into control group(0.3％sodium carboxymethyl cellulose),model group and low,high dose experimental groups(30,60 mg·kg-1 icotinib),8 rats in each group.PH rat model was established by single intraperitoneal injection of 60 mg·kg-1 MCT in model group and low,high dose experimental groups.The drug was administered continuously for 4 weeks after MCT injection.The hemodynamic indexes of each group were detected.Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL)staining was used to detect the apoptosis of right ventricular cardiomyocytes.The protein levels of B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved cysteine aspartic acid specific protease-3(cleaved-caspase-3),epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),optic atrophy 1(Opa1)and mitofusin 2(Mfn2)were detected by Western blot analysis.Results The right ventricular systolic pressure in low,high dose experimental groups and control group,model group were(38.58±4.98),(34.15±3.88),(23.66±2.45)and(45.07±5.78)mmHg;the mean pulmonary artery pressure were(27.85±3.77),(24.25±3.09),(17.33±2.46)and(33.07±4.15)mmHg;the right ventricle(RV)to left ventricle+septum were(36.38±5.51)％,(33.63±4.69)％,(22.25±2.96)％and(42.50±7.33)％;the RV to tibial length were(69.33±7.86),(62.69±7.17),(49.12±6.42)and(78.22±9.07)mg·cm-1.There were significant differences in the above indexes between low,high dose experimental groups and model group(all P＜0.01).There were significant differences in Bcl-2,Bax,cleaved caspase-3,p-EGFR,Opa1,Mfn2 between low,high dose experimental groups and model group(P＜0.05,P＜0.01).Conclusion Icotinib can inhibit right ventricular remodeling in PH rats induced by MCT,and its mechanism may be related to reducing the phosphorylation level of EGFR in the right ventricle,alleviating mitochondrial dysfunction and inhibiting cardiomyocyte apoptosis.

BackgroundIn China， the structure shift from just one-child family to both one-child and more-than-one-child families is happening. Exploring how the sibling relationships effect between adolescent personality impulsivity and aggressivity is of great significance for promoting adolescent mental health as well as maintaining social harmony and stability. ObjectiveTo investigate the effecting path of sibling relationships between personality impulsivity and aggressivity in adolescents， so as to provide references for the prevention of violent and aggressive behavior in adolescents. MethodsFrom February to April， 2023， a total of 1 200 students with sibling relationships from 12 primary and secondary schools in a county of Sichuan province were included by random sampling. Barratt Impulsivity Scale （BIS-11）， Chinese Version of Buss & Perry Aggression Questionnaire （AQ-CV）， and Sibling Relationship Questionnaire （SRQ） were used for cross-sectional investigation. Pearson Correlation Analysis was used to analyze the correlation between the scores of these scales. Bootstrap method was used to test the effecting path of sibling relationships between personality impulsivity and aggressivity. ResultsThe total score of BIS-11 was positively correlated with that of AQ-CV as well as the scores of conflict and competition dimensions in SRQ （r=0.485、0.276、0.280，P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.383， P<0.01）. The total score of AQ-CV was positively correlated with the scores of conflict and competition dimensions in SRQ （r=0.387， 0.340， P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.304， P<0.01）. Within SRQ， negative correlations could be observed between the score of warmth/intimacy and scores of conflict and competition （r=-0.307， -0.375， P<0.01）， whereas positive correlation could be observed between the score of conflict and that of competition （r=0.267， P<0.01）. The total effect of personality impulsivity level on aggressivity level in adolescent was 0.480 （P<0.01）. Sibling relationships played a mediating role between personality impulsivity and aggressivity in adolescents. Meanwhile， the indirect effect values of warmth/intimacy， conflict and competition were 0.054， 0.075 and 0.062， with the effect values accounting for 11.21%， 15.70% and 12.93%， respectively. ConclusionThe personality impulsivity of adolescents can directly affect their aggressivity， and sibling relationships may act as an important channel connecting personality impulsivity and aggressivity. ［Funded by 2023 Project of the Psychology and Behavioral Science Research Center of the Deyang Federation of Social Sciences （number， XLYXW2023305）］

Objective:To measure and compare the difference of personal attenuation rating (PAR) of the workers wearing foam earplugs before and after the training, and to evaluate the effect of ear protector wearing training on the noise protection.Methods:In February 2023, 94 workers exposed to noise in a machinery manufacturing factory were selected as subjects. The production noise in the workplace was measured and subjects were trained to wear earplugs. The PAR values of wearing 3M 1110 foam test earplugs were measured and recorded before and after the training by using the fit testing of hearing protection device. The differences between the actual PAR values with nominal values and the noise attenuation values in related standards were compared, and the protective effect of hearing protection device before and after training was evaluated.Results:The average age of the subjects was (36.76±11.48) years old, the average length of service was (16.34±11.64) years, and the average exposure time to noise was (15.67±11.64) years. The noise detection results of the subjects' posts were ranged from 80.1 to 94.3 dB (A). The results of subjects wore 3M 1110 foam test earplugs for fit testing showed that the binaural PAR value after training was (19.3±6.4) dB (A), which was significantly higher than that before training (11.1±7.4) dB (A) ( t=13.31, P<0.001). After training, 11 people (11.70%) could reach the corrected noise reduction value (NRR value), 26 people (27.66%) could reach the standard of single noise reduction value (SNR value) ×0.6, and 84 people (89.36%) could reach the standard of (NRR-7) /2. The under protection rate of hearing protectors after training (7.45%) was significantly lower than that before training (45.74%), and the difference of different protection levels before and after training was statistically significant (χ 2=40.83, P<0.001) . Conclusion:It is suggested that enterprises should use the fit testing instead of nominal value estimation to evaluate the noise reduction effect of hearing protection device. Special training on the selection and use of hearing protection device should be strengthened, so as to ensure that workers wear them correctly and improve the protective effect of hearing protection device.

Objective:To measure and compare the difference of personal attenuation rating (PAR) of the workers wearing foam earplugs before and after the training, and to evaluate the effect of ear protector wearing training on the noise protection.Methods:In February 2023, 94 workers exposed to noise in a machinery manufacturing factory were selected as subjects. The production noise in the workplace was measured and subjects were trained to wear earplugs. The PAR values of wearing 3M 1110 foam test earplugs were measured and recorded before and after the training by using the fit testing of hearing protection device. The differences between the actual PAR values with nominal values and the noise attenuation values in related standards were compared, and the protective effect of hearing protection device before and after training was evaluated.Results:The average age of the subjects was (36.76±11.48) years old, the average length of service was (16.34±11.64) years, and the average exposure time to noise was (15.67±11.64) years. The noise detection results of the subjects' posts were ranged from 80.1 to 94.3 dB (A). The results of subjects wore 3M 1110 foam test earplugs for fit testing showed that the binaural PAR value after training was (19.3±6.4) dB (A), which was significantly higher than that before training (11.1±7.4) dB (A) ( t=13.31, P<0.001). After training, 11 people (11.70%) could reach the corrected noise reduction value (NRR value), 26 people (27.66%) could reach the standard of single noise reduction value (SNR value) ×0.6, and 84 people (89.36%) could reach the standard of (NRR-7) /2. The under protection rate of hearing protectors after training (7.45%) was significantly lower than that before training (45.74%), and the difference of different protection levels before and after training was statistically significant (χ 2=40.83, P<0.001) . Conclusion:It is suggested that enterprises should use the fit testing instead of nominal value estimation to evaluate the noise reduction effect of hearing protection device. Special training on the selection and use of hearing protection device should be strengthened, so as to ensure that workers wear them correctly and improve the protective effect of hearing protection device.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective To construct SpyCatcher-mi3 nanoparticle vaccine delivery vectors,evaluate their role in enhancing the immunogenicity of the ovalbumin CD8+T-cell epitope peptide,OVA257-264,and determine its protective effect in a model which mice were immunized and subcutaneously challenged with E.G7-OVA tumor cells.Methods SpyCatcher-mi3 proteins were expressed by E.coli and purified by affinity chromatography and anion exchange chromatography sequentially.OVA257-264-SpyTag peptide was obtained by synthesis.The OVA257-264-mi3 nanoparticles were produced by the SpyTag/SpyCatcher system.The toxicity of OVA257-264-mi3 was evaluated using hemolysis assay,CCK-8 assay and mouse experiment.A total of 42 female SPF-grade C57BL/6 mice(6～8 weeks old,18～20 g)were randomly divided into OVA257-264-mi3,OVA257-264,and control groups,with 14 mice in each group.Then the mice in each group were immunized on days 0,14 and 28.In 14 d after the last immunization,the amounts of spot-forming cells(SFCs,indicating IFN-γ secreting cells in splenic lymphocytes)were determined using ELISpot assay to evaluate their immunogenicity.After the immunized mice were subcutaneously implanted with E.G7-OVA tumor cells,the antitumor effect of the vaccine in prophylactic xenograft tumor model was evaluate by observing tumor volumes with a caliper and tumor growth with MRI.Results Both SpyCatcher-mi3 and OVA257-264-mi3 could be self-assembled to form homogeneous and stable nanoparticles,with an average particle size of about 43.8 and 91.3 nm,respectively.The OVA257-264-mi3 was safe for in vitro and in vivo toxicity evaluation.The number of IFN--y secreting cells per 1 × 106 splenic lymphocytes reached 253 in the OVA257-264-mi3 group of mice,significantly higher than that in the OVA257-264 group and the Control group(P＜0.05).The tumor volume of mice in the OVA257-264-mi3 group was about 151.1 mm3 on day 22,which was significantly smaller than that of the OVA257-264 group and the Control group(P＜0.05),and the survival rate during the observation period reached 60％,which was significantly higher than that of the OVA257-264 groups(P＜0.05).Conclusion Nanoparticle vaccine OVA257-264-mi3 is successfully constructed,and it shows enhancing effect on the immunogenicity of the antigen epitope peptide,and exerts protective effect on prophylactic xenograft tumor model,providing a theoretical basis for the research of tumor neoantigen vaccines.

RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.

Objective:To explore the causal relationship between gastroesophageal reflux disease (GERD) and sleep disorder using Mendelian randomization (MR); To explore the diagnosis and treatment of sleep disorder with GERD by combining with the TCM theory that "gastric disharmony causing restless sleep".Methods:Genetic loci independent of each other and closely related to GERD were taken as instrumental variables by pooling data from a large-scale genome-wide association study. The causal relationship between GERD and sleep disorder was explored with Mendelian randomization methods, such as Inverse Variance Weighted (IVW), MR Egger, Weighted Median (WME), Simple Mode (SM), Weighted Mode (WM) and MR Multiple Effectiveness Residual Sum and Heteroscedasticity (MR-PRESSO) using OR as an evaluation index.Results:The results of the IVW method showed that GERD led to a 44.3% higher risk of developing sleep disorder ( P=4.96×10 -15, OR=1.443, 95% CI:1.317-1.582); horizontal pleiotropy was detected using the MR-Egger intercept, which was calculated to be P=0.646 ( P>0.05), proving that there was no horizontal pleiotropy in the results; Leave-one-out sensitivity test showed that the results were stable and there were no instrumental variables that strongly influenced the results. Conclusion:GRED is a risk factor for the development of sleep disorder, which is consistent with the TCM theory of "gastric disharmony causing restless sleep".

Deep vein thrombosis(DVT)is a common complication after surgery for lower limb fracture.It has the features of high morbidity,high disability rate and high mortality.At present,the measures for clinical prevention and treatment of post-operative DVT in lower limb fracture mainly include perioperative nursing,intervention with medical auxiliary instruments,western medicine prevention and treatment,traditional Chinese medicine(TCM)intervention,and patients'self-cooperation.The patients'self-cooperation is the basis for the smooth implementation of other measures for prevention and treatment,and the patients'active cooperation is the premise of achieving the efficacy of prevention and treatment.Perioperative nursing is helpful for the patients to understand the risk factors of postoperative DVT and the possible risks after the occurrence of DVT,guides the patients to choose the food,assists the patients to do postoperative exercises,improves the level of patients'hemorheological indexes,and reduce the incidence of postoperative DVT.Medical devices are helpful for assisting patients to do postoperative rehabilitation exercises,improving the levels of hemodynamic indicators,promoting patients'rehabilitation and reducing the incidence of postoperative DVT.Western medicines such as low molecular weight heparin,Rivaroxaban,Enoxaparin and other anticoagulant drugs can reduce the aggregation of coagulation factors and blood viscosity,and reduce the incidence of postoperative DVT.TCM interventions mainly include oral administration of Chinese medicine and external treatment such as acupuncture,moxibustion and massage.Oral administration of Chinese medicine is helpful for improving blood flow status.Acupuncture,moxibustion and massage are beneficial to the activation of the function of zang-fu organs,and can stimulate the healthy qi to improve the qi-blood state of the whole body.Each method of prevention and treatment has its advantages and disadvantages.In clinical application,reasonable prevention and treatment methods should be selected according to the specific conditions and individual conditions of the patients.TCM intervention of DVT can be performed in patients with lower limb fracture before and after surgery,and has the advantages of low cost and definite efficacy,which is worthy of continuous research and inheritance and innovation.

Objective To understand the cognition status of high-alert medications among medical staffs in Chongming District of Shanghai,and to explore its influencing factors and improvement countermeasures,so as to provide references for safe clinical use and effective control of such drugs.Methods Convenient sampling method was used to investigate among medical staffs in 9 hospitals in Chongming District from March to May 2022,the survey content included general information of medical staff and their awareness of high-alert medications.The orderly multi-classification logistic regression was used to analyze the influencing factors of the cognition of high-alert medications among medical staffs.Results A total of 605 valid questionnaires were collected,including 263 from doctors and 342 from nurses.The results of univariate analysis showed that there were significant differences in the grade distribution of high-alert medications management knowledge scores among doctors of different gender,education background and whether to partcipate in in-hospital training(P＜0.05).There were significant differences in the grade distribution of high-alert medications management knowledge scores among nurses with different education background,hospital level and whether to partcipate in in-hospital training(P＜0.05).There was significant differences in the grade distribution of high-alert medications pharmacy knowledge scores whether doctors participated in in-hospital training(P＜0.05).There were significant differences in the grade distribution of high-alert medications pharmacy knowledge scores among nurses with different education background,professional title,working years and whether to partcipate in in-hospital training(P＜0.05).The results of multi-factor Logistic analysis showed that whether doctors had participated in in-hospital training was an influential factor for and high-alert medications management knowledge score level(OR=0.003,95％CI 0.000 to 0.023,P＜0.001),high-alert medications pharmacy knowledge score level(OR=0.252,95％CI 0.147 to 0.431,P＜0.001).Whether nurses participated in in-hospital training(OR=0.022,95％CI 0.010 to 0.048,P＜0.001)and hospital level(OR=3.353,95％CI 1.639 to 6.855,P=0.001)were the influencing factors of nurses'high-alert medications management knowledge score level,and education background(OR=4.933,95％CI 1.452 to 16.760,P=0.011)and whether nurses participated in in-hospital training(OR=0.414,95％CI 0.239 to 0.717,P=0.002)were the influencing factors of nurses'high-alert medications pharmacy knowledge score level.Conclusion The cognition of high-alert medications among medical staffs in Chongming District is at a medium level on the whole.It is suggested to improve their cognitive ability and risk prevention awareness by improving their education,strengthening the knowledge education and training of high-alert medications,and homogenizing management,so as to ensure the safety of clinical drugs.