OBJECTIVES: To investigate the role of PTEN-induced putative kinase 1 (PINK1) in regulating the viability, migration, and apoptosis of colorectal cancer (CRC) cells, and to explore its potential epigenetic mechanisms. METHODS: PINK1 was overex-pressed or knocked down in HCT116 and DLD1 CRC cell lines using lentiviral vectors, with efficiency verified by qRT-PCR and Western blotting. Cell proliferation, colony formation, migration, and apoptosis were assessed using CCK-8, colony formation, wound healing, Transwell, and Hoechst 33258 staining assays, respectively. Protein levels of apoptosis-related and histone modification-related markers were analyzed by Western blotting. Genome-wide chromatin accessibility was profiled using ATAC-seq. RESULTS: PINK1 expression was significantly downregulated at both mRNA and protein levels in CRC tissues compared to normal tissues. PINK1 overexpression inhibited cell prolifera-tion, colony formation, and migration in HCT116 and DLD1 cells (all P<0.05), whereas PINK1 knockdown promoted these malignant phenotypes (all P<0.05). PINK1 overex-pression induced apoptosis, associated with decreased levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) and increased pro-apoptotic Bax (all P<0.05), without altering p53 expression. Mechanistically, PINK1 overexpression reduced the expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 27 trimethylation (H3K27me3), and increased the expression of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 27 acetylation (H3K27ac). It also downregulated key histone-modifying enzymes, including EZH2, EZH1, SUZ12, and histone deacetylase 3 (HDAC3) (all P<0.01). ATAC-seq revealed that PINK1 overexpression increased chromatin accessibility, particularly around transcription start sites. CONCLUSIONS PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

Objective To investigate the correlation between WT1,BCR-ABL genes and interleukin-6(IL-6),vascular endothelial growth factor(VEGF),plasma protein C(PC),plasma protein S(PS)in patients with myeloproliferative neoplasms(MPN).Methods A total of 54 MPN patients treated in this hospital from January 2021 to January 2024 were selected as the MPN group,and 54 healthy subjects undergoing physical examination during the same period were selected as the control group.The gene relative expression levels of WT1,BCR-ABL and levels of IL-6,VEGF,PC,and PS were detected and compared between the two groups.The correlations between WT1,BCR-ABL gene relative expression levels and IL-6,VEGF,PC,PS levels were analyzed,and the diagnostic efficacy of WT1 and BCR-ABL genes for MPN was evaluated by receiver operat-ing characteristic(ROC)curve.Results Compared with the control group,the gene relative expression levels of WT1,BCR-ABL and the levels of IL-6 and VEGF in the MPN group were higher,while the levels of PC and PS were lower,with statistically significant differences(P<0.05).Pearson correlation analysis showed that WT1 and BCR-ABL gene relative expression levels were positively correlated with IL-6 and VEGF levels,and negatively correlated with PC and PS levels(P<0.05).The combined use of WT1 and BCR-ABL genes has higher diagnostic efficacy for MPN than single indicators,with an area under the curve(AUC)of 0.833 and a sensitivity of 88.69%.Conclusion The relative expression levels of WT1 and BCR-ABL genes are correlated with IL-6,VEGF,PC,and PS levels in MPN patients.The combination of WT1 and BCR-ABL genes can effec-tively diagnose MPN.

Objective To explore the clinical efficacy of fluoxetine hydrochloride capsules and escitalopram oxalate tablets in the treatment of first-episode depression disorder.Methods Eighty patients with first-episode depression disorder who were hospitalized in the 14th district of Integrated Traditional Chinese and Western Medicine of Xiamen Xianyue Hospital from February to November 2023 were selected,and divided into fluoxetine hydrochloride capsules group(n=40)and escitalopram oxalate tablets group(n=40)according to random number method;Conducted the Hamilton depression scale(HAMD)estimates before treatment and four weeks after treatment,to analyze and compare the clinical efficacy of two groups.Results After four weeks of treatment,the HAMD scores of all patients significantly decreased compared to before treatment in this group(P＜0.01);There was no statistically significant difference between two groups(P＞0.05).There was no statistically significant difference in the total effective rate between two groups(P＞0.05).Conclusion Escitalopram oxalate tablets and fluoxetine hydrochloride capsules were both effective in treatment of the first-episode depression disorder patients,and the total effective rates of them were similar.

Objective To evaluate the diagnostic value of ischemia-modified albumin(IMA)and the crea-tine kinase(CK)index in acute ischemic stroke(AIS).Methods According to the inclusion and exclusion cri-teria,totally 149 newly diagnosed and untreated AIS patients hospitalized in Henan Provincial People's Hospi-tal from October 2021 to October 2022 were selected as the AIS group.Additionally,156 healthy people who underwent the physical examination during the same period were selected as the control group.Activity levels of IMA,CK,creatine kinase-MB(CK-MB),lactate dehydrogenase(LDH)and hydroxybutyrate-dehydrogen-ase(HBDH)were measured using the Abbott C1600 biochemical analyzer,and the CK index(ratio of CK-MB to CK)was calculated.Relative risk factors were analyzed,receiver operating characteristics(ROC)curve was constructed,data were analyzed using SPSS27.0.1,graphs were plotted using GraphPad Prism 9.4.1,and differences in area under the curve(AUC)were compared using MedCalc(version 20.0.22).Results The AIS group exhibited significantly higher levels of IMA,CK-MB,and the CK index,and significantly lower levels of CK compared to the control group(all P＜0.05).Univariate logistic regression analysis revealed that both IMA and the CK index were risk factors for AIS(both P＜0.001).After adjusting for gender and age in a multivariate binary logistic regression analysis,IMA emerged as an independent risk factor for AIS(OR=1.901,95％CI:1.649-2.190,P＜0.001).IMA,CK-MB and CK index in the AIS group were significantly higher than those in the control group,and CK levels were significantly lower than those in the control group,and the differences were statistically significant(P＜0.05).Univariate Logistic regression analysis showed that IMA and CK index were risk factors for AIS(P＜0.001).After adjusting for sex and age in multivariate binary Logistic regression analysis,IMA was an independent risk factor for AIS(OR=1.901,95％CI:1.649-2.190,P＜0.001).The ROC curve demonstrated that AUC,the sensitivity and the specificity of sin-gle detection for IMA were 0.922,81.2％,and 90.4％,respectively.There was no significant difference compared to combined detection using IMA+CK index or IMA+CK index+CK(all P＞0.05).Conclusion IMA is an independent risk factor for AIS,which has strong diagnostic value and is worthy of clinical application.

Objective:To investigate the changes in synaptic transmission function of hippocampal dentate gyrus granule cells in depression model mice induced by chronic unpredictable mild stress (CUMS) and to explore the effect of exercise on it.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were randomly compartmentalised into control group (CTRL group), model group (CUMS group), model + exercise group (CUMS+ EXE group), and model + fluoxetine group (CUMS+ FLX group), with 12 mice in each group. CUMS method was used for preparating the depression model for 21 d. Mice in the CUMS+ EXE group were given roller locomotion training and mice in the CUMS+ FLX group were given fluoxetine intraperitoneally (10 mg/kg) daily during the modelling period, and the other two groups were administrated intraperitoneally with equal volume of 0.9% NaCl solution.Sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST) were used to detect depressive-like behavior, and open field test (OFT) was used to detect anxiety-like behavior. Whole-cell recordings were used to detect spontaneous excitatory postsynaptic currents (sEPSC), spontaneous inhibitory postsynaptic currents (sIPSC), miniature excitatory postsynaptic currents (mEPSC), and miniature inhibitory postsynaptic currents (mIPSC) in hippocampal dentate gyrus granule cells.One-way ANONA was performed to analyze the data by SPSS 23.0.Results:(1) There were statistically significant differences among the 4 groups of mice in terms of activity time in the center, total distance of OFT and sugar preference rate( F=37.85, 18.41, 28.81 all P<0.01). The activity time in the center((47.81±3.51)s) and total distance((19.63±1.24)m) of OFT and sugar preference rate((55.63±9.11)%) in the CUMS group were lower than those in the CTRL group (all P<0.01), while those in the CUMS+ EXE group((59.87±3.25)s, (23.18±1.24)m, (69.03±8.22)% respectively) were higher than those in the CUMS group (all P<0.05).The sugar preference rate of the CUMS+ EXE group was lower than that in the CTRL group and CTRL+ FLX group (both P<0.01). The differences in immobility time of TST and FST were statistically significant among the 4 groups of mice ( F=113.70, 56.97, both P<0.01). The immobility time of TST and FST of the CUMS group was lower than that of mice in the CTRL group (both P<0.01), while that in the CUMS+ EXE group were lower than that in the CUMS group (both P<0.05) and higher than that in the CTRL group (both P<0.01). (2)There were statistically significant differences in frequency, amplitude and quantification of sEPSC among the 4 groups of mice ( F=22.02, 17.98, 179.00, all P<0.01). The sEPSC frequency, amplitude, and quantification of mice in the CUMS group were lower than those in the CTRL group (all P<0.05), while those in the CUMS+ EXE group were higher than those in the CUMS group (all P<0.05) and lower than those in the CTRL group and CUMS+ FLX group (all P<0.05). The differences in frequency and quantification of sIPSC among the 4 groups of mice were statistically significant ( F=22.12, 184.80, both P<0.01). The sIPSC frequency and quantification of mice in the CUMS group were higher than those in the CTRL group (both P<0.05), while those in the CUMS+ EXE group were lower than those in the CUMS group (both P<0.05) and higher than those in the CTRL group (all P<0.05).The difference in quantification of sEPSC/sIPSC ratios among the 4 groups of mice was statistically significant ( F=267.10, P<0.01). The quantification of sEPSC/sIPSC ratio of mice in the CUMS group was lower than that in the CTRL group ( P<0.05). The quantification of sEPSC/sIPSC ratio of mice in the CUMS+ EXE group was higher than that in the CUMS group ( P<0.05) and lower than that in the CTRL group and CUMS+ FLX group(both P<0.05). (3) The differences in mEPSC frequency and amplitude among the 4 groups of mice were statistically significant ( F=25.07, 23.57, both P<0.01). The mEPSC frequency and amplitude in the CUMS group were lower than those in the CTRL group (both P<0.05), while those in the CUMS+ EXE group were higher than those in the CUMS group (both P<0.05) and lower than those in the CTRL group and CUMS+ FLX group(all P<0.05). The difference in mIPSC frequency among the 4 groups of mice was statistically significant ( F=13.79, P<0.01). The mIPSC frequency of mice in the CUMS+ EXE group was lower than that in the CUMS group ( P<0.05) and higher than that in the CTRL group ( P<0.05). Conclusion:Exercise can partially improve depressive-like behaviours and enhances hippocampus granule cell synaptic transmission in depression model mice.

Objective:To investigate the effects of enriched environment on the behavior of depressive-like mice induced by chronic stress and the synaptic transmission function of hippocampal pyramidal neurons.Methods:Thirty-six 7-week-old SPF grade male C57BL/6J mice were divided into control group, model group and enriched environment group according to the random zone method, with 12 mice in each group.The mice in model group and enriched environment group were subjected to chronic unpredictable mild stress to establish depression models.During the modeling period, the mice in enriched environment group lived in the enriched environment for 6 hours per day, and lived in the routine environment for the rest time just like the mice in control group and model group.The depressive behaviors of mice were detected by sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST).The motor function and anxious behavior of mice were detected by open field test (OFT) and the cognitive function was detected by Morris water maze test.In vitro electrophysiological techniques were used to record field excitatory post-synaptic potentials (fEPSP) in the hippocampus, and whole-cell recording was used to record spontaneous excitatory post-synaptic currents (sEPSC) and miniature excitatory post-synaptic currents (mEPSC) in hippocampal pyramidal neurons.Statistical analysis was conducted by SPSS 23.0 software.Multiple group comparisons of data were conducted by one-way ANOVA and repeated measures ANOVA.Results:(1) Behavioral results showed statistically significant differences among the three groups in terms of total activity time in the central area of OFT, sugar water preference rate of SPT and immobility time of TST and FST ( F=17.12, 26.07, 41.13, 60.18, all P<0.01).The activity time in the central area of OFT and sugar water preference rate of model group were lower than those in the control group (both P<0.01), and the immobility time of TST and FST were higher than those in the control group (both P<0.01).The activity time in the central area of OFT ((56.56±3.47) s) and sugar water preference rate ((71.22±8.37) %) of enriched environment group were higher than those in the model group((52.56±3.47) s, (59.53±8.72)%) (all P<0.05), and the immobility time of TST ((94.19±10.77) s) and FST ((76.98±12.10) s) were lower than those in the model group ((104.58±8.24) s, (111.41±9.56) s)(all P<0.05).(2)The results of spatial learning memory showed that there was a significant difference of group and time interaction effects for latency to find the platform ( F=12.02, P<0.01), and the latency to find the platform in model group was higher than that in control group and enriched environment group (both P<0.01).The results of spatial exploration showed that there were statistically significant differences in the target quadrant residence time and the times crossing the platform among the three groups( F=19.67, 20.27, both P<0.01).The both indexes in the model group were lower than those in control group and enriched environment group (all P<0.01).(3) The results of electrophysiological experiment showed that the interaction effect of fEPSP between groups and stimulations intensity among the three groups was significant( F=1.86, P<0.01).At the stimulation level of 150 mA and 200 mA, the fEPSP of the model group was lower than those of control group and enriched environment group (all P<0.05).(4)The results of the long-term potentiation(LTP) showed a statistically significant difference among the three groups( F=15.32, P<0.01).The LTP of the model group mice ((137.42±4.48)%) was lower than those of the control group ((156.62±4.79)%) and the enriched environment group ((147.86±9.14)%) (both P<0.05).(5) The whole-cell recordings results showed that there was a statistically significant difference in the frequencies of sEPSC and mEPSC among the three groups ( F=15.30, 13.72, both P<0.01).The sEPSC and mEPSC frequencies of the model group mice ((0.60±0.31) Hz, (0.63±0.26) Hz) were lower than those of the control group ((1.27±0.46) Hz, (1.02±0.28) Hz) and the enriched environment group ((0.96±0.45) Hz, (0.83±0.22) Hz) (all P<0.05). Conclusion:Environmental enrichment can alleviate the depressive behaviors induced by chronic stress and enhance cognitive performance, hippocampal pyramidal neuron synaptic transmission and synaptic plasticity in depressive-like mice.

Objective To observe the value of enhanced CT radiomics combined with clinical indicators for predicting of extramural venous invasion(EMVI+)of colorectal cancer.Methods Data of 131 patients with colorectal cancer proved by surgery pathology were retrospectively analyzed.The patients were divided into training set(n=92,including 44 cases with EMVI+ and 48 with EMVI-)and test set(n=39,including 23 cases with EMVI+ and 16 with EMVI-)at the ratio of 7∶3.The best radiomics features were extracted based on preoperative portal-venous phase CT to construct a radiomics model.Univariate and multivariate logistic regression analysis were used to analyze the clinical,CT and pathological data of the training set,and the independent predictors of colorectal cancer EMVI were screened to build a clinical model.Finally a combined model was established based on radiomics and clinical model.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting EMVI+ in colorectal cancer.Calibration curve and decision curve analysis were used to evaluate the calibration degree and clinical practicability of the models.Results Four best radiomics features were selected to construct the radiomics model.Carbohydrate antigen(CA)19-9 and CA 72-4 were both independent predictors of EMVI+ for colorectal cancer(OR=1.033,1.285,both P＜0.05).The AUC of combined model(AUC=0.908)for predicting EMVI+ of colorectal cancer in training set was higher than that of radiomics and clinical models(AUC=0.825,0.770,P=0.017,0.003).In test set,the AUC of radiomics,clinical and combined models was 0.751,0.632 and 0.799,respectively,not being statistical different between each pair(all P＞0.05).The radiomics model and combined model both had good calibration degree.Taken ＞0.1 in training set and ＞0.12 in test set as the thresholds,the clinical net benefit of combined model was higher.Conclusion Enhanced CT radiomics combined with clinical indicators could effectively predict EMVI+of colorectal cancer.

Objective To explore and implement a differentiated management strategy for multi-campus hospitals to improve patient experience and satisfaction,and achieve the goal of homogenized management.Methods In December 2021,the Picker Patient Experience Questionnaire was used to survey the patient experience at 3 campuses of a tertiary A hospital in Hangzhou,and the reasons for the differences were analyzed.Based on policy document reviews,special group discussions,and expert meetings,differentiated management strategy for multi-campus hospitals was formulated.The patient experience and satisfaction before(December 2021)and after(December 2023)the implementation were compared.Results After the application of the one-hospital multi-campus difference management strategy,the overall medical experience score of the patients in the 3 campus was(58.54±2.36)points,which was higher than(58.13±3.24)points before the application(t=-3.223,P=0.001),and there was no statistically significant differences among the patients in the 3 campuses(F=0.781,P=0.458).After the application of the management strategy,the overall satisfaction score of the patients in the 3 campus was(98.44±6.22)points,which was higher than(97.98±6.87)points before the application of the management strategy(t=-2.490,P=0.013),and there was no statistical significance among the patients in the 3 campus(F=1.128,P=0.324).The number of banners and letters of commendation received by the 3 campuses increased from 1 661 before the application to 2 190 after the application,with a growth rate of 31.85％.Conclusion Differentiated management in a multi-campus hospital,aiming at homogenized quality through differentiated strategies,is practicable and can significantly improve the patient experience and satisfaction across different campuses.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.