Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Background There are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. Objective To establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. Methods Cells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L⁻¹ of the diluted NaClO (100 mmol·L⁻¹) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L⁻¹ NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca²⁺ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. Results Compared with 0 μmol·L⁻¹, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L⁻¹ NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L⁻¹ NaClO, showing about 70% of normal cell viability (P<0.01). So 30 min 50 μmol·L⁻¹ NaClO treatment was selected for the subsequent experiment. The experimental results found that compared with the 0 μmol·L⁻¹ NaClO treatment group, the number of apoptotic cells increased (P<0.05), the mitochondrial membrane potential decreased (P<0.01), the intracellular Ca²⁺ concentration increased (P<0.05), the cellular ROS level increased (P<0.05), the mitochondrial ROS level increased (P<0.01), and the MDA content increased (P<0.01) in the NaClO treatment group.. Conclusion The study has successfully established a model of BEAS-2B injury induced by NaClO, and found that NaClO can lead to cell damage by inducing apoptosis and oxidative stress in BEAS-2B cells. According to the results, there are two possible reasons. First, NaClO solves in water to form hypochlorous acid (HClO) which is oxidative and increases the intracellular ROS level after entering cells, leading to cellular oxidative stress. Second, HClO enters cells to directly attack the mitochondrial membrane, resulting in the imbalance of potential inside and outside the mitochondrial membrane, and apoptosis caused by Ca²⁺ efflux.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Nowadays,the application of ultrasound is not only used in clinical imaging,but also extended in the study of drug delivery.Diagnostic ultrasound combined with microbubbles can effectively open the biological barriers,which can enhance the targeted delivery of drugs and be beneficial to the combination of ultrasound and disease treatment.This review summarizes the biological effects of ultrasound,the characteristics of ultrasound microbubbles and the potential ability that solving the biological barrier problems in cancer therapy by using ultrasound targeted microbubble destruction,hoping to provide some reference for the further development of therapeutic ultrasound as a safe and effective drug targeted delivery strategy.

Objective:To assess the validity and reliability of the depression and somatic symptoms scale among patients with coronary heart disease.Methods:Totally 246 patients with coronary heart disease were assessed with depression and somatic symptoms scale (DSSS), Hamilton depression rating scale for depression (HAMD) and patients’ health questionnaire depression scale-9 item (PHQ-9). The structural validity was evaluated with exploratory factor analysis and confirmatory factor analysis. The validity as a screening tool was evaluated with the gold standard diagnosed by psychiatrists who were trained with the mini international neuropsychological interview (MINI) according to ICD-10. Receiver operating characteristic (ROC) curve was used to identify cutoff scores for depression. Cronbach α coefficient was used to evaluate the internal consistency.Results:Exploratory factor analysis yielded two factors: depression factor and somatic factor, and the cumulative variance was 51.8%. The fitting indexes of confirmatory factor analysis were as follows: χ2/ df=3.636, RMR=0.077, RMSEA=0.104, IFI=0.804, TLI=0.781, CFI=0.802. The intraclass correlation coefficient of DSSS and HAMD was 0.54. The area under ROC curve (AUC) was 0.828, and the best boundary value was 17 points (sensitivity and specificity: 81% and 75%, respectively). The total scores and subscale scores for internal consistency of DSSS were higher in the depression group than those in the non-depression group ( P<0.01). Cronbach α coefficient for internal consistency of DSSS was 0.917. Conclusion:The DSSS has good validity and reliability among patients with coronary heart disease for screening depression, and can be used to screen depression among patients with coronary heart disease in general hospital.

Objective:To observe the feasibility of evaluating right ventricular (RV) function by the method based on left ventricle (LV) pressure-strain ring (PSL) technique in patients with systemic lupus erythematosus (SLE), and to evaluate the efficacy of non-invasive PSL in the diagnosis of dysfunction of both LV and RV.Methods:Thirty-nine patients were enrolled with SLE who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from March 2020 to September 2021 and 57 sex- and age-matched healthy controls underwent assessment by conventional echocardiography, two-dimensional speckle tracking imaging (2D-STI) and myocardial work (MW). The echocardiographic parameters were compared between the groups. The correlations between RVMW parameters and conventional echocardiographic parameters, and between MW parameters and SLEDAI-2K score were analyzed by Spearman correlation analysis.Results:①The two groups did not show any difference at the conventional echocardiographic parameters of the LV systolic function ( P>0.05). In the SLE group, tricuspid regurgitation maximal velocity (TR V max) and right ventricular index of myocardial performance (RIMP) increased, tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular S′ (S′ tv) decreased (all P<0.05), and others did not show statistical difference (all P>0.05). ②The 2D-STI parameters: There were no significant differences in left ventricular global longitudinal strain (LV GLS) ( P>0.05), however RVGLS decreased ( P<0.05). ③The MW parameters of LV and RV: including global constructive work (GCW), global work index (GWI), global wasted work (GWW), and global work efficiency (GWE). In SLE group, LV GWE, RV GWE decreased and LV GWW, RV GWW increased ( P<0.05), others were no significant differences ( P>0.05). ④The correlation analysis: RV GWI positively correlated with TR V max ( rs=0.481). RV GCW positively correlated with TR V max ( rs=0.587). RV GWW positively correlated with right atrial area (RAA) and TR V max ( rs=0.429, 0.610), negatively correlated with S′ tv ( rs=-0.342). RV GWE positively correlated with S′ tv ( rs=0.326) and negatively correlated with RAA ( rs=-0.462) (all P<0.05). SLEDAI-2K score was negatively correlated with LV GLS ( rs=-0.333) and LV GWI ( rs=-0.326) ( P<0.05). Conclusions:The study has shown the impaired systolic function of both LV and RV in patients with SLE. PSL technique, especially RVMV based on LV PSL technique might emerged as a novel measure to evaluate systolic dysfunction in SLE patients.

The laccase (PpLAC) gene family members in peach fruit were identified and the relationship between their expression pattern and chilling induced browning were investigated. The study was performed using two varieties of peaches with different chilling tolerance, treated with or without exogenous γ-aminobutyric acid (GABA) during cold storage. Twenty-six genes were screened from the peach fruit genome. These genes were distributed on 6 chromosomes and each contained 5-7 exons. The PpLAC gene family members shared relatively similar gene structure and conserved motifs, and they were classified into 7 subgroups based on the cluster analysis. Transcriptome sequencing revealed that the expression levels of PpLAC7 and PpLAC9 exhibited an increasing pattern under low temperature storage, and displayed a similar trend with the browning index of peach fruit. Notably, GABA treatment reduced the degree of browning and inhibited the expression of PpLAC7 and PpLAC9. These results suggested that PpLAC7 and PpLAC9 might be involved in the browning of peach fruit during cold storage.
Food Storage ; Fruit/genetics* ; Laccase/genetics* ; Prunus persica/genetics*

Objective To explore the clinical feature,treatment and prognosis of incidental prostate cancer(IPC) after transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods From January 2009 to April 2017,24 cases undergoing TURP for benign prostatic hyperplasia and being diagnosed with prostate cancer(T1a-T1b) was retrospectivey analysed,who aged from 62 to 84 years (mean 71.8 years).Digital rectal examination (DRE) showed prostate medium texture,smooth surface,and no nodules.Ultrasound presented no low echo nodules in the prostate.Prostate volumes were 19.2-93.4 ml,with median of 40.1 ml.PSA were 1.81-9.11 ng/ml,with median of 4.12 ng/ml.The patients with PSA between 6-10 ng/ml accepted prostate biopsy,and pathological results were negative.Results The The pathology of TURP specimens in 24 cases were diagnosed prostate cancer (21 cases of T1a,3 cases of T1b).According to the new WHO/ISUP classification group,there were 18 cases of hierarchical group 1,3 cases of hierarchical group 2,1 case of hierarchical group 3,2 cases in hierarchical group 4.All patients were treated with hormonal therapy,and 7 cases (5 cases of hierarchical group 1,and 2 cases of hierarchical group 2) underwent laparoscopic radical prostatectomy (LRP) after 3 months of hormonal therapy.The specimens of prostatectomy were examined by whole-mount serial,showing 3 cases of prostate cancer (T1a) with negative margin,and 4 cases of benign prostate cells.They were followed up for 5-82 months with median of 43.5 months.No biological progression or tumor progression was found,and,1 case died of colon cancer after 26 months of follow-up.The patients' age and Gleason score of stage T1b were higher than that of stage T1a.Prostate volume and preoperative PSA had no statistically significant difference between the two stages.Conclusions The patients' age and Gleason score of stage T1b were higher than that of stage T1b.The proportion of residual tumor following TURP was high.The prognosis of incidental prostate cancer was good by hormonal therapy or radical prostatectomy.

Objective To compare the effects of propofol combined with fentanyl or dezocine on painless abortion and the influence on body movement.Methods From July 2016 to May 2017,240 patients with voluntary painless abortion who aged 19-45 years old in the Second People's Hospital of Linhai,were randomly divided into 3 groups according to the digital table ,with 80 cases in each group.D group was given propofol and dezocine ;F group was given propofol combined with fentanyl ;C group was the control group and was treated with propofol intravenous anesthesia,the three groups were given propofol added according to the specific situation.The operative time,recovery time and the total amount of propofol were compared among the three groups ;and the pain visual analogue scale (VAS) at 0min,15min,30min,1h,3h were comparedamong the three groups ;The incidence of respiratory depression and other adverse reactions were statistically analyzed in three groups.Results The operation time,recovery time,the total dosage of propofol in D group were (4.5 ±0.7)min,(1.2 ±0.3)min and (136.8 ±14.5)mg,respectively, which in F group were (4.6 ±0.8)min,(1.3 ±0.2)min and (139.6 ±12.1)mg,respectively,there were no statisti-cally significant differences between the two groups (all P＞0.05).The recovery time and total dosage of propofol in D group and F group were lower than those of C group [(2.4 ±0.6) min,(168.7 ±18.9) mg](t＝25.298,27.287, 11.977,27.287,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h,3h in D group were lower than those in F group and group (t＝34.785,25.044,25.043,22.349,28.622,48.809,42.278,40.000,42.278, 40.000,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h in F group were lower than those of C group(t＝36.978,24.406,19.846,24.406,all P ＜0.05).The incidence rates of nausea,sedentary,respiratory depression,hypotension in D group were 1.3%(1case),2.5%(2cases),1.3%(1case),0.0%(0cases), resperctively,which in F group were 0.0%(0cases),3.8%(3cases),3.8%(3cases),2.5%(2cases),which in D group,F group were lower than those in C group [6.3%(5cases),16.3%(13cases),11.3%(9cases),15.0%(12cases)](χ2＝3.925,3.657,3.925,3.657,5.889,3.152,3.152,3.657,all P＜0.05).Conclusion Propofol combined with dezocine and fentanyl used in painless abortion have good effect ,and the body movement is less ,but propofol combined with dezocine has less postoperative pain degree.

To summarize the breeding and identification of Wuzhishan miniature pig models with α-l,3-galactosyltransferase (GGTA1) gene-knockout (GTKO).Methods The breeding and reproduction perform of GTKO Wuzhishan miniature pigs were assessed and the quantity of piglets was counted.The GTKO Wuzhishan miniature pig models with GGTA1gene knockout were validated by polymerase chain reaction(PCR).The αGal phenotype of peripheral blood mononuclear cells (PBMC) in human,wild-type Wuzhishan miniature pigs and GTKO Wuzhishan miniature pigs was detected by fluorescent microscope and flow cytometry.Routine blood test parameters were statistically compared between the GTKO and wild-type Wuzhishan miniature pigs.Results The inheritance of GGTA1 genotype complied with Mendel's law.Flow cytometry detected no fluorescent expression of PBMC in GGTA1-/-pig models,which were consistent with the genotype identification results.The mean piglets of the primiparous GTKO Wuzhishan miniature pigs were (6.8±1.8) and (8.3±2.2) for the multiparous Wuzhishan miniature pigs.No statistical significance was noted in routine blood test parameters between the GTKO and wild-type Wuzhishan miniature pigs (all P＞0.05).Conclusions Stable inheritance and normal reproductive capacity are observed in two generations of Wuzhishan miniature pigs continuously.GTKO Wuzhishan miniature pig is a reliable donor for heterogeneous organ transplantation.