OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

The relationship between antagonism and symbiosis exists not only in the biological world,but also among the subspecialties of large tertiary grade A general hospitals.In the context of symbiosis theory,the following recommendations based on the four basic elements of subspecialty symbiosis systems were proposed to provide a theoretical basis for exploring the path of high-quality development of subspecialties:enhance the capacity of the symbiosis unit itself and clarify the role of the unit;establish efficient information system and make full use of management platform;improve interest coordination mechanism and strengthen inter-subspecialty ties;implement relevant support policies and solid sense of symbiotic to synergy provide a theoretical basis for exploring pathways for high quality development of subspecialties.

Aim To explore the mechanism of oxidized lipoprotein(a)(oxLp(a))inducing pyroptosis of vascu-lar endothelial cells.Methods After incubating human umbilical vein endothelial cells(HUVEC)with 100 mg/L ox-Lp(a)for 24 hours,Western blot and RT-qPCR was used to detect pyroptosis related proteins,pro-inflammatory cytokines,mitochondrial related proteins NRF1,NRF2,PGC-1α and mitochondrial gene cytochrome b(CYTB),ELISA was used to detect the levels of inflammatory factors,scanning electron microscopy was used to detect cell membrane rup-ture,transmission electron microscopy was used to detect mitochondrial morphology,Hoechst33342/PI staining was used to detect cell apoptosis,MitoSOX probe was used to detect mitochondrial reactive oxygen species(mtROS),Flu-4AM probe was used to detect calcium ions,JC-1 probe was used to detect mitochondrial membrane potential(MMP),and Calcein AM staining was used to detect mitochondrial permeability transition pore(mPTP).Transfecting HUVEC with CYTB overexpressing lentivirus and analyzing its effects on oxLp(a)induced pyroptosis and mitochondrial function.Results After treatment with oxLp(a),the expression of NLRP3,pro-Caspase-1,Caspase-1,GSDMD and GSDMD-N proteins re-lated to pyroptosis were significantly increased(P＜0.05);the protein and mRNA levels of CYTB and pro-inflammatory cy-tokine IL-1β,IL-18 were significantly increased(P＜0.05).Small pores appeared on the cell membrane,the percentage of PI stained positive cells significantly increased(P＜0.05).OxLp(a)significantly inhibited the expression of mito-chondrial related proteins NRF1,NRF2 and PGC-1α,and the expression of mitochondrial gene CYTB,promoted an in-crease in mtROS generation,Ca2+overload,a decrease in ATP levels,a decrease in MMP,an increase in mPTP values,and abnormal mitochondrial morphology.After transfection with pHelper 2.0 lentivirus vector overexpressing CYTB,it was found that oxLp(a)induced HUVEC pyroptosis and mitochondrial morphological and functional abnormalities were par-tially reversed by overexpression of CYTB.Conclusion oxLp(a)promotes mitochondrial morphological and functional abnormalities and induces HUVEC pyroptosis by downregulating CYTB.

Abstract: Objective　This study aims to investigate the drug resistance, resistance mechanisms, and serotype epidemiological features of clinically isolated Streptococcus pneumoniae (SP) in Shanxi Province. Methods　SP strains were isolated between January 2021 and July 2023 from Shanxi Provincial People's Hospital. An automatic microbiological identification and drug sensitivity analysis system was used to identify strains and conduct antibiotic susceptibility assay. The species identification was also carried out using a MALDI-TOF mass spectrometer, optochin assay, and amplification of the CPSA gene. Finally, the polymerase chain reaction (PCR) technique was implemented for drug-resistant and virulence gene detection and serotyping. Results　A total of 117 strains were isolated including 115 strains (98.3%) being erythromycin-resistant Streptococcus pneumoniae (ERSP). The ERSP was composed of 114 macrolide-lincosamide-streptogramin B (MLSB) resistant strains, carrying the ermB (114/114) and mefA (42/114) gene, and one M-resistant strain absent of ermB and tetM. The most common pneumococcal six serotypes in ERSP strains were 19F, 3, 34, 19A, 6A/6B, and 23F, respectively, totaling 71 strains (61.7%). Compared with pediatric and adult, serotype 19F in geriatric patients was the dominant type with a significant difference (χ2=6.315, P=0.043). Compared with adult patients, the strains isolated from pediatric and elderly patients showed a higher rate of insensitivity (resistance and intermediate) to oral penicillin (χ2=7.277, P=0.026). Serotype 19F strains showed high insensitivity to oral penicillin (81.0%), compound sulfamethoxazole (100.0%), tetracycline (94.7%), and ceftriaxone (9.5%). The serotypes 19A and 23F strains also showed high insensitivity to penicillin (>70%), tetracycline (100%) and compound sulfamethoxazole (>85%). However, serotype 3 strains had low insensitivity to oral penicillin (8.3%), ceftriaxone (0%), and compound sulfamethoxazole (27.3%). There were 42 strains positive for ermB+mefA, of which serogroup 19 was the main type, accounting for 64.3% (27/42). Of these strains, 88.1% (37/42) carried ply, lytA, and HylA genes simultaneously. Conclusion　Drug resistance to ERSP still to be a serious problem for human health. There are differences in serotype distribution in terms of age, resistance genes, and drug resistance. Therefore, the vaccination of pneumococcal conjugate vaccine 13 (PCV13) is an essential and effective measure to prevent SP infection in this region.

Objective:To explore the detection rate of non-caseating granuloma under endoscopy in patients with Crohn′s disease and its influencing factors, in order to improve the pathological diagnosis rate of Crohn′s disease.Methods:From July 2016 to April 2021, at the First Affiliated Hospital of Soochow University, 199 patients who met the clinical diagnostic criteria for Crohn′s disease and underwent endoscopic biopsy were collected. The detection rates of non-caseating granulomas in all patients with Crohn′s disease, in different types (primary and recurrent) and whether the biopsy site included the colon were analyzed. According to whether non-caseating granulomas were detected by endoscopic biopsy, the patients were divided into the detected group and the undetected group. The clinical data of the two groups of patients were compared, which included gender, age, course of disease, body mass index, smoking status, clinical manifestations (abdominal pain, diarrhea, gastrointestinal bleeding, perianal lesions, weight loss, fever, intestinal obstruction), therapeutic medication (5-aminosalicylic acid, immunosuppressants, glucocorticoid, biological agents, exclusive enteral nutrition), history of bowel surgery, laboratory examination results (hemoglobin, platelet count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate, albumin), endoscopic manifestation (ulcer, fistula, stricture), simplified Crohn′s disease activity index (CDAI), total number of biopsy samples, and site of biopsy. Chi-square test, continuity correction chi-square test, Mann-Whitney U test and Fisher exact test were used for statistical analysis, and logistic regression analysis was used to analyzed the influencing factors of detection of non-caseating granulomas under endoscopy. Results:Among the 199 patients with Crohn′s disease, 67 cases were detected with non-caseating granuloma (detected group), and the overall detection rate was 33.7% (67/199); 132 cases were not detected with non-caseating granuloma (undetected group). The detection rate of non-caseating granulomas in patients with primary Crohn′s disease was higher than that of recurrent patients (39.9%, 59/148 vs. 15.7%, 8/51), and the detection rate of non-caseating granulomas in patients with Crohn′s disease whose biopsy site included the colon was higher than that of patients whose biopsy site did not include colon (64.1%, 25/39 vs. 26.3%, 42/160), and the differences were statistically significant ( χ2=9.93 and 20.12 , P=0.002 and <0.001). The age of patients in the detected group was younger than that of the undetected group; the course of disease of the detected group was shorter than that of the undetected group; the proportions of patients with abdominal pain and history of biological treatment in the detected group were lower than those of the undetected group; the simplified CDAI score of the detected group was higher than that of the undetected group; and the total number of biopsy samples of the detected group was more than that of the undetected group (30.0 years old (25.0 years old, 37.00 years old) vs. 32.0 years old (28.0 years old, 41.0 years old); 1.0 year (0.0 year, 3.0 years) vs. 2.0 years (0.0 year, 5.0 years), 61.2%, 41/67 vs. 75.8%, 100/132; 0, 0/67 vs. 10.6%, 14/132; 5.00 (2.00, 7.00) vs. 4.00 (2.00, 6.00); 10 (8, 12) vs. 6 (3, 9)), and the differences were statistically significant ( Z=-2.29, -1.99, χ2=4.56, corrected χ2=6.11, Z=-2.05, -5.64, all P<0.05). The case number of biopsy location in terminal ileum, colon, ileocolon, upper gastrointestinal tract, terminal ileum+ upper gastrointestinal tract, ileocolon+ upper gastrointestinal tract in the detected group was 36, 4, 18, 1, 5 and 3, respectively, compared with those of undetected group (94, 4, 8, 11, 13 and 2), the difference was statistically significant (Fisher′s exact test, P<0.001). The results of multivariate logistic regression analysis suggested that the total number of biopsy samples, whether the biopsy site included the colon and disease type were independent influencing factors for the detection of non-caseating granulomas under endoscopy in patients with Crohn′s disease (regression coefficients=0.157, 0.979 and -0.960, OR=1.171, 2.662 and 0.383; 95% confidence interval 1.067 to 1.284, 1.140 to 6.214, 0.158 to 0.929; P=0.001, 0.024 and 0.034). Conclusions:For endoscopic examination in patients with suspected Crohn′s disease, the total number of biopsy samles should be increased as much as possible, and biopsy should be performed at the colonic lesions, in order to improve the detection rate of non-caseating granulomas under endoscopy thereby providing more pathological evidence for the diagnosis of Crohn′s disease.

Objective:To explore the influence of mindfulness on perceived stress in psychiatric nurses and the mediating effect of resilience.Methods:A total of 427 psychiatric nurses from a psychiatric hospital in Beijing were selected.Five-facet mindfulness questionnaire(FFMQ), Chinese-version perceived stress scale (CPSS) and Connor-Davidson resilience scale (CD-RISC) were used in this survey.Pearson correlation analysis and multiple stepwise regression analysis were performed using SPSS 24.0.And mediating effect was performed using AMOS 24.0.Results:The total score of psychiatric nurses' perceived stress was (37.89±7.16). Among all psychiatric nurses, 66.74% were under high pressure and 20.84% were under great pressure.The perceived stress was negatively correlated with mindfulness(123.69±10.82, r=-0.65, P<0.01) and resilience(85.40±17.87, r=-0.67, P<0.01), and mindfulness was positively correlated with resilience ( r=0.50, P<0.01). The direct effect of mindfulness on perceived stress was -0.15, the indirect effect was -0.34, and the total effect was -0.49. Conclusion:Resilience plays a partial mediating role between mindfulness and perceived stress psychiatric nurses.

As an effective anticancer drug, the clinical limitation of doxorubicin (Dox) is the time- and dose-dependent cardiotoxicity. Yes-associated protein 1 (YAP1) interacts with transcription factor TEA domain 1 (TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced

Objective    To investigate the effectiveness and safety of totally endoscopic transmitral myectomy (TETM) for hypertrophic obstructive cardiomyopathy (HOCM), comparing with traditional sternotomy modified Morrow procedure (SMMP). Methods    Thirty-eight patients with HOCM who needed surgical intervention were selected from our hospital in 2019, including 14 males and 24 females, with an average age of 56 (44-68) years. According to the operation method, they were divided into a TETM group (n=18) and a SMMP group (n=20). Appropriate patients  were screened by propensity matching scores. Finally, the clinical data of two matched groups were compared and

Objective:To explore the relationship between early maladaptive schemas, defense styles and mental health in patients with depression, and to investigate the mediating effects of defense styles between early maladaptive schemas and mental health.Methods:A total of 87 outpatients with depression were assessed with the Young schema questionnaire-short form 2(YSQ-SF2), defense style questionnaire(DSQ), symptom checklist-90(SCL-90) and Beck depression inventory(BDI). SPSS Process program and Bootstrap method were used to explore the mediating effect of defense styles.Results:The scores of abandonment/instability were higher in females than those in males (2(0.5, 4), 0(0, 1.25), Z=-2.963, P=0.003) while the score of emotional inhibition was higher in males than in females (1(0, 3), 0(0, 2), Z=-2.318, P=0.02). The total score of SCL-90 was positively predicted by vulnerability to harm or illness and emotional deprivation, with an explanatory variation rate of 27.7%.The number of SCL-90 positive items was positively predicted by social isolation/alienation and abandonment/instability, with an explanatory variation rate of 19.3%.Immature defense styles fully mediate the relationship between social isolation/alienation and mental health, as well as between abandonment/instability and mental health. Conclusion:Social isolation/alienation and abandonment/instability affect the mental health of patients with depression by the mediating effect of immature defense styles.