Objective:To investigate the effects of pulsed electric field (PEF) combined with gemcitabine (GEM) on the viability and stemness of HCCC-9810 cholangiocarcinoma stem cells.Methods:HCCC-9810 cholangiocarcinoma stem cells were established in serum-free, cytokine-rich medium and divided into four groups: the control group, GEM group, PEF group, and the pulsed electric field combined with gemcitabine (PEF+ GEM) group. Cell proliferation was detected using the Cell Counting Kit-8 (CCK8) assay. Cell viability and apoptosis rate were measured by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression of stemness marker proteins CD133 and Octamer-binding transcription factor 4 (OCT4), as well as the expression of β-catenin, was detected by Western blotting.Results:Regarding cell viability, the GEM, PEF, and PEF+ GEM groups showed significantly lower cell viability and higher apoptosis rate than the control group at 24 h, 48 h, and 72 h (all P<0.05). At 48 h and 72 h, the PEF+ GEM group showed significantly lower cell viability (7.2%±0.3% and 5.9%±0.8%, respectively) than the GEM group (50.7%±0.6% and 31.0%±1.2%, respectively) and the PEF group (12.2%±0.2% and 12.8%±0.2%, respectively) (all P<0.05). Regarding stemness inhibition, the PEF+ GEM groups showed significantly lower expression levels of CD133 and OCT4 at 24 h, 48 h, and 72 h compared with the control group (all P<0.05). Notably, at 48 h, the PEF+ GEM group showed a significantly lower expression level of the OCT4 (0.61±0.02) than the GEM group (0.87±0.08) and the PEF group (1.00±0.10) ( P<0.01). Furthermore, at 24 h and 48 h, the GEM, PEF, and PEF+ GEM groups showed significantly lower expression levels of β-catenin compared with the control group (all P<0.05). Conclusion:Pulsed electric field combined with gemcitabine therapy demonstrated more effective anti-proliferation and cancer stemness inhibition effects on HCCC-9810 cholangiocarcinoma stem cells compared with either monotherapy.

Objective:To evaluate the effectiveness of remote management based on unmet health needs self-monitoring reports in patients with colorectal cancer.Methods:A total of 124 colorectal cancer inpatients admitted to the First Affiliated Hospital of Zhengzhou University from October 2022 to September 2023 were selected using convenience sampling and randomly divided into a control group and an intervention group (62 patients each). The control group received routine follow-up care, while the intervention group received remote management based on self-monitoring reports of unmet health needs in addition to routine follow-up, over a 3-month period. To evaluate the outcomes, the Health Literacy Management Scale (HeLMS), the Health Promoting Lifestyle Profile-II (HPLP-II), the Short Form of the Unmet Needs Survey (SF-SUNS), and the Self-Care Self-Efficacy Scale (SCSES) were compared between two groups.Results:After the intervention, the intervention group showed significantly higher scores in HeLMS, HPLP-II, and SCSES compared to their baseline values and the control group ( P<0.05). Additionally, the SF-SUNS score was significantly lower in the intervention group post-intervention than both its baseline and the control group post-intervention ( P<0.05) . Conclusions:Remote management based on unmet health needs self-monitoring reports effectively improves health literacy, promotes healthier lifestyles, enhances self-management efficacy, and reduces levels of unmet health needs in patients with colorectal cancer.

Objective:To investigate the effects of pulsed electric field (PEF) combined with gemcitabine (GEM) on the viability and stemness of HCCC-9810 cholangiocarcinoma stem cells.Methods:HCCC-9810 cholangiocarcinoma stem cells were established in serum-free, cytokine-rich medium and divided into four groups: the control group, GEM group, PEF group, and the pulsed electric field combined with gemcitabine (PEF+ GEM) group. Cell proliferation was detected using the Cell Counting Kit-8 (CCK8) assay. Cell viability and apoptosis rate were measured by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression of stemness marker proteins CD133 and Octamer-binding transcription factor 4 (OCT4), as well as the expression of β-catenin, was detected by Western blotting.Results:Regarding cell viability, the GEM, PEF, and PEF+ GEM groups showed significantly lower cell viability and higher apoptosis rate than the control group at 24 h, 48 h, and 72 h (all P<0.05). At 48 h and 72 h, the PEF+ GEM group showed significantly lower cell viability (7.2%±0.3% and 5.9%±0.8%, respectively) than the GEM group (50.7%±0.6% and 31.0%±1.2%, respectively) and the PEF group (12.2%±0.2% and 12.8%±0.2%, respectively) (all P<0.05). Regarding stemness inhibition, the PEF+ GEM groups showed significantly lower expression levels of CD133 and OCT4 at 24 h, 48 h, and 72 h compared with the control group (all P<0.05). Notably, at 48 h, the PEF+ GEM group showed a significantly lower expression level of the OCT4 (0.61±0.02) than the GEM group (0.87±0.08) and the PEF group (1.00±0.10) ( P<0.01). Furthermore, at 24 h and 48 h, the GEM, PEF, and PEF+ GEM groups showed significantly lower expression levels of β-catenin compared with the control group (all P<0.05). Conclusion:Pulsed electric field combined with gemcitabine therapy demonstrated more effective anti-proliferation and cancer stemness inhibition effects on HCCC-9810 cholangiocarcinoma stem cells compared with either monotherapy.

Objective:To evaluate the effectiveness of remote management based on unmet health needs self-monitoring reports in patients with colorectal cancer.Methods:A total of 124 colorectal cancer inpatients admitted to the First Affiliated Hospital of Zhengzhou University from October 2022 to September 2023 were selected using convenience sampling and randomly divided into a control group and an intervention group (62 patients each). The control group received routine follow-up care, while the intervention group received remote management based on self-monitoring reports of unmet health needs in addition to routine follow-up, over a 3-month period. To evaluate the outcomes, the Health Literacy Management Scale (HeLMS), the Health Promoting Lifestyle Profile-II (HPLP-II), the Short Form of the Unmet Needs Survey (SF-SUNS), and the Self-Care Self-Efficacy Scale (SCSES) were compared between two groups.Results:After the intervention, the intervention group showed significantly higher scores in HeLMS, HPLP-II, and SCSES compared to their baseline values and the control group ( P<0.05). Additionally, the SF-SUNS score was significantly lower in the intervention group post-intervention than both its baseline and the control group post-intervention ( P<0.05) . Conclusions:Remote management based on unmet health needs self-monitoring reports effectively improves health literacy, promotes healthier lifestyles, enhances self-management efficacy, and reduces levels of unmet health needs in patients with colorectal cancer.

Objective:To explore the clinical characteristics and predictive factors for plastic bronchitis (PB) in children with severe Mycoplasma pneumoniae pneumonia (SMPP). Methods:A retrospective cohort enrolled children with a clinical diagnosis of SMPP who were treated at the Department of Respiratory Medicine of Tianjin Children′s Hospital Machang District from January 1, 2018, to October 31, 2023. According to the bronchoscopy and pathological examination results, the patients were divided into 142 cases in the PB group and 274 cases in the non-PB group. The clinical manifestations, laboratory data, imaging findings, and treatments were analyzed.Mann-Whitney U test and Chi-square test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the risk factors. The receiver operating characteristic (ROC) curve was used to explore the predictive value of PB in SMPP. Results:Among 416 SMPP children, there were 197 males and 219 females; PB group 142 cases, non-PB group 274 cases, the age of disease onset was (6.9±2.9) years and (6.6±2.8) years in the PB group and the non-PB group respectively. The incidence of wheezing symptoms, hypoxemia, heat peak >40 ℃, the duration of fever, neutrophil-lymphocyte ratio, mean platelet volume, C-reactive protein, procalcitonin, interleukin-6, alanine transaminase, aspartate aminotransferase and ferritin were higher in the PB group (16 cases (11.3%) vs. 15 cases (5.5%), 14 cases (9.9%) vs. 12 cases (4.4%), 57 cases (40.1%) vs. 67 cases (24.5%), 10 (8, 12) vs. 9 (8, 12) d, 6.1 (4.1, 13.1)×10 9vs. 5.0 (3.7, 6.8)×10 9/L, 10.2 (9.6, 10.8) vs. 9.4 (8.9, 10.1) fl, 33.4 (16.0, 67.5) vs. 23.0 (10.4, 56.1) mg/L, 0.24 (0.12, 0.48) vs. 0.16 (0.09, 0.31) μg/L, 39.9 (25.1, 81.4) vs. 31.3 (18.3, 59.3) ng/L, 16.0 (12.0, 29.0) vs. 14.0 (10.0, 24.3) U/L, 38.5 (28.0, 52.5) vs. 33.0 (25.0, 44.0) U/L, 233 (136, 488) vs. 156 (110, 293) μg/L, χ2=4.55, 4.79, 11.00, Z=2.25, 4.00, 6.64, 2.76, 2.98, 3.09, 2.22, 2.62, 4.18, all P<0.05). Multivariate Logistic regression analysis showed that the dyspnea ( OR=2.97, 95% CI 1.35-6.55, P=0.007), the diminution of respiration ( OR=2.40, 95% CI 1.27-4.52, P=0.006), neutrophil-lymphocyte ratio (NLR) ( OR=2.07, 95% CI 1.71-2.51, P<0.001), lactate dehydrogenase (LDH) ( OR=1.01, 95% CI 1.00-1.01, P<0.001), mean platelet volume/platelet count (MPV/PLT) ( OR=1.39, 95% CI 1.13-1.71, P=0.002), pleural effusion ( OR=2.23, 95% CI 1.21-4.13, P=0.011),≥2/3 lobe consolidation ( OR=1.84, 95% CI 1.04-3.00, P=0.039) and atelectasis ( OR=1.98, 95% CI 1.02-3.48, P=0.044) were independent predictors of PB in children with SMPP. ROC curve analysis showed that the cut-off values for NLR, LDH and MPV/PLT in the diagnosis of PB were 2.79 (sensitivity 0.89, specificity 0.69, area under the curve (AUC)=0.86, P<0.001), 474 U/L (sensitivity 0.63, specificity 0.65, AUC=0.70, P=0.003) and 0.04 (sensitivity 0.75, specificity 0.53, AUC=0.68, P=0.005) respectively. Children in the PB group had longer hospital stays and corticosteroid treatment course than those in the non-PB group, the proportion of children in the PB group who received bronchoscopy treatment twice or more was higher (9 (8, 12) vs. 8 (6, 10) d, 7 (5, 8) vs. 6 (5, 7) d, 128 cases (90.1%) vs. 218 cases (79.6%), 106 cases (74.7%) vs. 54 cases (19.7%), Z=6.70, 5.06, χ2=7.48, 119.27, all P<0.05). Conclusions:The dyspnea, respiration diminution, NLR level elevation (>2.79) and pleural effusion were predictive factors for PB in children with SMPP. This provides a basis for the early identification of PB in children with SMPP.

Objective:To explore the value of circ_0054633 in early diagnosis and prognosis prediction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children with severe pneumonia.Methods:A retrospective case-control study was conducted on children with diagnosed severe pneumonia admitted to Tianjin Children's Hospital from July 1, 2022, to February 29, 2024. The clinical data was collected by electronic medical record system and clinical follow-up, including gender, age, lung injury prediction score (LIPS), pediatric critical illness score (PCIS), serum circ_0054633, interleukin-6 (IL-6), the indicators of the arterial blood-gas analysis, oxygenation index (PaO 2/FiO 2) within 24 hours of admission and the survival status of 28 days. According to whether ALI/ARDS occurred, they were divided into the ALI/ARDS group and the non-ALI/ARDS group. The differences of clinical data between the two groups were compared, and multivariate Logistic regression was used to analyze the risk factors for ALI/ARDS in children with severe pneumonia. The receiver operator characteristic curve (ROC curve) will be used to explore the early diagnostic value of ALI/ARDS in children with severe pneumonia. The patients of ALI/ARDS were divided into mild group, moderate group and severe group according to the level of PaO 2/FiO 2. The levels of serum circ_0054633 and IL-6 in various severity ALI/ARDS were compared. The differences of serum circ_0054633, IL-6 levels, PCIS score and LIPS score were compared between the two groups of ALI/ARDS patients according to different prognoses in 28 days, as well as the correlation between various risk factors and circ_0054633. Results:A total 74 children with severe pneumonia were included, with 34 cases in the ALI/ARDS group and 40 cases in the non-ALI/ARDS group. In ALI/ARDS group, there were 9 cases in the mild group, 15 cases in the moderate group and 10 cases in the severe group; while 12 cases died and 22 cases survived after 28 days. The serum circ_0054633, IL-6 level and LIPS score were higher in the ALI/ARDS group than the non-ALI/ARDS group, while the PCIS score was lower, and the two groups had significant difference. Multivariate Logistic regression analysis showed that circ_0054633 was independent predictors of ALI/ARDS in children with severe pneumonia [odds ratio ( OR) = 3.853, 95% confidence interval (95% CI) was 1.912-7.805, P = 0.017]. ROC curve analysis showed that the cut-off values for circ_0054633 in the diagnosis of ALI/ARDS were 3.955, sensitivity was 79.4%, specificity was 92.5%, area under the ROC curve (AUC) was 0.892. The serum circ_0054633 and IL-6 levels were higher in the children who died in 28 days than the children who were survived, while the PCIS score was lower, and the two groups had significant difference. Spearman correlation analysis showed that the level of circ_0054633 in children with ALI/ARDS was positively correlated with 28-day mortality and IL-6 ( r value was 0.675, 0.763, respectively, all P < 0.001), but negatively correlated with PCIS score ( r = -0.626, P < 0.001), while no significant correlation with LIPS score ( r = 0.389, P = 0.023). Conclusion:The level of serum circ_0054633 has a better value in early diagnosis and prognosis prediction of ALI/ARDS caused in children with severe pneumonia.

Objective:To explore the involvement of miR-126 and the role of mammalian target of rapamycin (mTOR)/hypoxia-induced factor 1 α (HIF-1 α) pathway in regulating human umbilical cord mesenchymal stem cells (hUCMSCs) exosomes (Exo) on vascular endothelial growth factor (VEGF)-A levels in high glucose-induced human retinal vascular endothelial cells (HRECs).Methods:The hREC was cultured in EGM-2-MV endothelial cell culture medium with 30 mmol/L glucose and placed in hypoxic cell incubator by 1% oxygen concentration. The cell model of high glucose and low oxygen was established. After modeling, divided HRECs into Exo group, phosphate buffer saline (PBS) group, PBS+anti-miR126 group, Exo+anti-miR126 group, PBS+anti-mTOR group, and PBS+anti-HIF-1 α group. High-glucose and hypoxia-induced hREC in the PBS and Exo groups were respectively co-cultured with PBS and 100 μg/ml hUCMSC Exo. PBS+anti-mTOR group, PBS+anti-HIF-1 α group: 500 nmol/L mTOR inhibitor ADZ2014, 25 μmol/L HIF-1 α inhibitor YC-1 pretreatment for hREC 12 h, and then co-culture with PBS after High-glucose and hypoxia-induced. PBS+anti-miR126 group, Exo+anti-miR126 group: miR-126 LNA power inhibitor probe was transfected with high glucose, and co-cultured with PBS and hUCMSC Exo 6 h after transfection. Real-time polymerase chain reaction (qPCR) measured miRNA-126 expression levels in PBS, and Exo groups for 0, 8, 16 and 24 h. After 24 h of co-culture, the levels of mTOR and HIF-1 α in the cells of PBS and Exo groups were detected by immunofluorescence, Western blot and qPCR, respectively. Western blot, qPCR detection of VEGF-A expression levels in cells of the PBS+anti-mTOR and PBS+anti-HIF-1 α groups. The expression of VE GF-A, mTOR, and HIF-1 α mRNA was measured in cells of PBS+anti-miR126 group and Exo+anti-miR126 group by qPCR. Comparison between two groups was performed by t-test; one-way ANOVA was used for comparison between multiple groups. Results:At 0, 8, 16 and 24 h, the relative mRNA expression of miR-126 gradually increased in the Exo group ( F=95.900, P<0.05). Compared with the PBS group, The mTOR, HIF-1 α protein ( t=3.466, 6.804), mRNA in HRECs in the Exo group, VEGF-A mRNA expression ( t=8.642, 7.897, 6.099) were all downregulated, the difference was statistically significant ( P<0.05). The relative expression level of VEGF-A protein ( t=3.337, 7.380) and mRNA ( t=8.515, 10.400) was decreased in HRECs of the anti-mTOR+PBS group and anti-HIF-1 α+PBS group, differences were statistically significant ( P<0.05). The relative expression of VEGF-A, mTOR, and HIF-1 α mRNA was significantly increased in the cells of the Exo+anti-miR126 group, the differences were all statistically significant ( t=4.664, 6.136, 6.247; P<0.05). Conclusions:miR-126 plays a role in regulating the effect of hUCMSCs exosomes on VEGF-A levels in high glucose-induced HRECs via mTOR-HIF-1 α pathway.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective To observe the image characteristics ofmultispectral scanning laser imaging (MSLI) and OCT in patients with pregnancy induced hypertension syndrome (PIHS).Methods A total of 112 patients (224 eyes) of PIHS patients diagnosed in Obstetrics Department of Tianjin First Central Hospital from May 2016 to May 2017 were included in this study.The average age of the patients was 27.00±2.14 years.The average course of the disease was 15.00 ±8.27 days.There were 174 eyes in 87 patients of blurred vision,dazzling and visual fatigue consciously.All patients performed BCVA,direct ophthalmoscope,B ultrasound,confocal scanning laser Ophthalmoscope (cSLO) and spectral-domain OCT (SD-OCT).SD-OCT was performed with Spectralis HRA+OCT from Heidelberg Company in Germany to acquire tomographic images.Using Herdelberg's colorful program (MultiColor) based on cSLO and operating in accordance with standard methods,one scan simultaneously obtained blue light reflection based on 488 nm,green light reflection based on 515 nm,and infrared reflection based on 820 nm,synthesis to MSLI.Fundus abnormalities were classified into arterial spasm (stage Ⅰ),arteriosclerosis (stage Ⅱ),and retinopathy (stage Ⅲ).OCT examination was divided into normal and abnormal cases according to the abnormality of retinal morphology and thickness.Results Of the 224 eyes,68 eyes (30.36％) showed normal fundus examination and 156 eyes (69.64％) showed abnormal fundus performance.Among them,28 eyes were stage Ⅰ (17.95％);40 eyes were stage Ⅱ (25.64％);88 eyes were stage Ⅲ (56.41％).Thirty-six eyes (16.07％) showed normal fundus and 188 eyes (83.93％) showed abnormal performance with OCT.Of the 188 eyes with abnormal fundus performance,86 eyes (45.74％) had retinal neuroepithelial serous detachment;56 eyes (29.79％) had RPE detachment;optic disc edema,bulge,and local reflexes in the retinal nerve fiber layer were enhanced and/or the thickness increased in 46 eyes (24.47％).In MSLI,48 eyes (21.43％) showed normal fundus;176 eyes (78.57％) showed abnormal performance.Retinal edema was showed in green on MSLI,serous retinal neuroepithelial layer detachment,RPE layer detachment,retinal nerve fiber layer thickening,accompanied by changes in local retinal structure.The higher the degree of bulge,the darker the color.Consistent with the range of retinal edema revealed by SD-OCT.Conclusions MSLI and SD-OCT images show highly consistent lesions in PIHS patients.MSLI can more clearly show superficial and deep retinal lesions.

A great number of studies have demonstrated functional abnormalities in children with attention-deficit/hyperactivity disorder (ADHD), although conflicting results have also been reported. And few studies analyzed homotopic functional connectivity between hemispheres. In this study, resting-state functional magnetic resonance imaging (MRI) data were recorded from 45 medication-naïve ADHD children and 26 healthy controls. The regional homogeneity (ReHo), degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were compared between the two groups to depict the intrinsic brain activities. We found that ADHD children exhibited significantly lower ReHo and DC values in the right middle frontal gyrus and the two values correlated with each other; moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD children, which was negatively related with anxiety scores of Conners' Parent Rating Scale (CPRS-R) and positively related with completed categories of Wisconsin Card Sorting Test (WCST). Our results might suggest that less spontaneous neuronal activities of the right middle frontal gyrus and the bilateral occipital lobes in ADHD children.