ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Objective To construct a time series analysis fusion tool using multisource internet data and then accurately predict the incidence trend of hepatitis in Chongqing.Methods The incidence rate of hepatitis were obtained from the database of the Centre for Health and Disease Control.Air pollutant data were obtained from the official website of the China Environmental Monitoring Station,climate data were obtained from the National Meteorological Galaxy Center,and network index data were obtained through Baidu search engine.The time duration was from November 2013 to May 2023.Based on existing time series analysis methods,multisource data were used to correct the residual part of the decomposition model.A delayed input neural network(DINN)was constructed based on the respective advantages of non autoregressive(NAR)and long short-term memory(LSTM)recurrent neural networks.Afterwards,optimization modules such as the Nutcracker Optimization Algorithm(NOA)and Joint Quantile Huber Loss(JQHL)were added to the foundation,and then DINN+was constructed.Results Compared to common single-input models and synchronous multi-input models,DINN achieved the best prediction performance.After adding hyperparameters and loss function optimization,the predictive performance of DINN+was further improved,with a mean-square error(MSE)of 0.170 9,a mean absolute error(MAE)of 0.461 2,a root-mean-square error(RMSE)of 0.582 1,a mean absolute percentage error(MAPE)of 0.062 6,and a R-square(R2)of 0.884 0 in a testing set.Conclusion Based on the ideas of diverse methods and multidimensional data fusion,we propose a DINN+optimization model with good accuracy and generalization ability on the basis of previous time series analysis.This model enriches and supplements the methodological research content of using multisource data to calibrate infectious disease time series prediction analysis and can serve as a new benchmark for future analysis of influencing factors and trend prediction of infectious disease public health.

Objective To construct a prognosis prediction model of primary liver cancer after surgical treatment based on synthetic minority over-sampling technique(SMOTE)algorithm and machine learning model.Methods A retrospective cohort study was conducted on 4 297 patients with primary liver cancer from the surveillance,epidemiology,and end results(SEER)database.One-Hot Encoding and Multiple Imputation were used to preprocess the collect data,and SMOTE algorithm was employed to solve the imbalance of data categories.The obtained clinical variables were included in the machine learning model.Based on decision tree(DT),random forest(RF),gradient boosting decision tree(GBDT)and eXtreme Gradient Boosting(XGBoost),a prognostic prediction model(SMOTE+DT/RF/GBDT/XGBoost)was build,and then the best prediction model was determined by comparing the performance of various models.Finally,a prognostic analysis system for primary liver cancer was developed based on the optimal model,which was then visualized.Results The combination model SMOTE+RF showed the best predictive performance,with higher area under the curve(0.895),accuracy(0.811)and precision(0.806)than those of other models in receiver operating characteristic curve(ROC)analysis.Conclusion The SMOTE+RF prognostic prediction model can effectively predict the survival outcome of patients with primary liver cancer.

Objective To investigate the influencing factors for tendency towards depression in college students having music listening habits with music APP,and develop a prediction model and further optimize it.Methods A total of 1 157 college students were subjected with convenient sampling and surveyed with questionaires between April and May 2023.Univariate analysis and logistic regression analysis were employed to identify the influencing factors.Then a prediction model was constructed based on these factors.SMOTEENN over-sampling algorithm was utilized to enhance the dataset and construct the prediction model.Results Logistic regression analysis revealed that female(OR=1.730,95％CI:1.257～2.396),senior grade(OR=2.649,95％CI:1.198～7.506),postgraduate grade(OR=2.041,95％CI:1.231～3.885),major in Science(OR=1.573,95％CI:1.052～2.350),listening for a duration of 0.5～2 h(OR=1.661,95％CI:1.011～2.695),music style of melancholy(OR=2.668,95％CI:1.701～4.226)and of nostalgia(OR=1.751,95％CI:1.086～2.837),and frequency of comments on 0～5％of songs(OR=2.938,95％CI:1.018～8.417)were independent risk factors for depressive tendency.Time since listening to music for 1～3 years(OR=0.547,95％CI:0.347～0.872),listening to music from 14:00 to 18:00(OR=0.375,95％CI:0.167～0.845)and 18:00 to 21:00(OR=0.313,95％CI:0.148～0.671),and preference for Chinese style songs(OR=0.711,95％CI:0.541～0.941)were independent protective factors.The logistic early warning model based on SMOTEENN algorithm demonstrated optimal predictive performance with an AUC value of 0.923.Conclusion Our constructed logistic regression model has identified 9 independent influencing factors associated with depression tendency among college students.The early warning model based on SMOTEENN algorithm can predict the depression tendency more accurately for college students.

Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cere-bral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expres-sion of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluo-rescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedif-ferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,signifi-cantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydro-choloride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedif-ferentiation and may be used to treat ischemic stroke.

ObjectiveTo develop a rehabilitation program of nature posture treatment (NPT) suspension therapy based on the International Classification of Functioning, Disability and Health-Children and Youth version (ICF-CY) framework, and apply it to neurodevelopmental disorders. MethodsThe ICF-CY theoretical group (group A) and NPT suspension therapy group (group B) were established. Group A searched literature from common databases, to extract high-frequency words related to suspension therapy and match with categories of ICF-CY, to develop ICF-CY theoretical framework of the NPT suspension therapy. Group B developed specific rehabilitation procedures and training items based on the framework to compose the training pool. A total of 110 children aged less than six years with neurodevelopmental disorders and associated motor impairments were selected from outpatient or inpatient of the First Affiliated Hospital of Xinxiang Medical University, between October, 2019 and October, 2022. They were randomly divided into control group (n = 55) and clinical group (n = 55), who received routine neurodevelopmental therapy and NPT suspension therapy program based on ICF-CY, respectively, for a week. The incidence of satisfaction, acceptance and adverse events were observed. ResultsTwo cases in the control group and four cases in the clinical group dropped down. For the clinical group, the incidence of satisfaction was 98% (50/51), with acceptance of 96% (49/51), and one adverse event occurred. For the control group, the incidence of both the satisfaction and acceptance was 100%, and no adverse event occurred. There was no significant difference in the incidence of satisfaction, acceptance and the adverse event (P > 0.05). ConclusionThe NPT suspension therapy program based on the ICF-CY framework is safe and acceptable for children with neurodevelopmental disorders.

Objective: To investigate the relationship between the use of earphone and hearing impairment and its influencing factors among students aged 14-28, so as to provide a reference for appropriate earphone usage and hearing impairment prevention. Methods: A cross sectional survey was conducted through the questionnaire star platform, and 983 students aged 14 to 28 were recruited across China by snowball sampling during April 3 to May 1, 2022. The χ 2 test was used to identify indicators affecting hearing, the Logistic regression model was used to further selection. Results: There were 366 students with hearing impairment, accounting for 37.23%. Univariate analysis showed significant differences in hearing impairment by gender, earphone usage duration and volume, wearing during sleep, and replacement frequency ( χ 2=6.03, 6.86, 14.87, 12.22, 11.15, P <0.05). The Logistic regression model analysis showed that girls ( OR=1.43, 95%CI =1.10-1.88), maximum earphone volume ( OR=3.08, 95%CI = 1.56- 6.08), earphone usage for >1.5-3 h each time ( OR=1.44, 95%CI =1.04-1.99), sleep with headphone ( OR= 1.53 , 95%CI = 1.11- 2.11) were positively associated with hearing impairment ( P <0.05), earphone replacement every 4-<6 months ( OR= 0.38, 95%CI =0.17-0.86) and earphone replacement every six months or longer ( OR=0.39, 95%CI =0.18-0.85) were negatively associated with hearing impairment ( P < 0.05 ). Conclusion Students aged 14 to 28 earphone usage shows adverse impact on hearing. When using earphone, it is recommended to limit time spent on earphone usage, low the volume of earphone, avoid sleeping with earphone and replace earphone frequently.

Objective:To construct a practical education training quality evaluation system that can monitor the entire training process for the master of public health, and to provide a basis for improving the public health education system.Methods:Based on the survey of the current status of the master of public health, combined with the literature survey, the focus group discussion and the expert forum, an evaluation system was established, and the weight coefficient of each index was determined by the analytic hierarchy process (AHP). All data were entered by Excel double-person, and matlabR2018a was used to calculate the weight, and determine the maximum characteristic root of the matrix, consistency index and consistency ratio.Results:The evaluation index system consisted of 7 first-level indicators and 24 second-level indicators. The average authority coefficient of 32 experts was 0.791. The top three items with the highest weight in the first-level indicators were mentor guidance (0.213), professional practice (0.157) and scientific research topics (0.149). The weight coefficient consistency ratio ( CR) was 0.040, showing that the consistency test passed ( CR<0.1). Conclusion:The educational quality evaluation system of the master of public health constructed by the institute is scientific, and the weight of the evaluation index reflects the focus of the postgraduate training process of the master of public health, which can provide a reference for improving the quality of public health professionals.

Objective:To observe the effects of Xiaoqinglong Decoction and Qingqi Huatan Pills on interleukin-1β(IL-1β)-induced mucushypersecretion model of human airway epithelial H292 cellsand related molecules of nuclear factor-κB/microRNA-494 (NF-κB/miR-494) signaling pathway, and to explore the mechanism of the two medicines in improving pathological airway mucus.Methods:Methyl thiazolyl tetrazolium (MTT) colorimetric method was used to detect the effects of different concentrations of Xiaoqinglong Decoction and Qingqi Huatan Pills on the activity of H292 cellsinduced by IL-1β, and the appropriate concentration was selected for subsequent experiments. Cells were randomly divided into blank group, IL-1β model group (5 μg/L IL-1β), NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) group (5 μg/L IL-1β+100 μmol/L PDTC), Xiaoqinglong Decoction (5 μg/L IL-1β+1 000 mg/L Xiaoqinglong Decoction) and Qingqi Huatan Pill group (5 μg/L IL-1β+1 000 mg/L Qingqi Huatan Pills). 5 μg/L IL-1β was used to induce H292 cells for 24 hours to establish a model of airway epithelial mucus hypersecretion. Enzyme linked immunosorbent assay (ELISA) method was used to detect the levels of mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α) and IL-8 and the synthesis of intracellular MUC5AC and cystic fibrosis transmembrane conductance regulator (CFTR). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of MUC5AC mRNA, CFTR mRNA, miR-494. Western blotting was used to detect protein expression of key proteins (p65) and NF-κB inhibitors (IκB) in NF-κB signaling pathway.Results:Xiaoqinglong Decoction and Qingqi Huatan Pills with the concentration of 1 000 mg/L were selected for the follow-up experiment. Compared with the blank group, the levels of MUC5AC, TNF-α and IL-8 were significantly increased in the model group, intracellular MUC5AC protein content and mRNA expression were also significantly increased, intracellular CFTR protein content and mRNA expression were significantly decreased, and intracellular p65 protein expression was significantly up-regulated, the expression of IκB protein was significantly down-regulated, and the expression of miR-494 was significantly increased. Compared with the model group, the levels of MUC5AC, TNF-α and IL-8 were significantly reduced in PDTC group, Xiaoqinglong Decoction group and Qingqi Huatan Pill group, intracellular MUC5AC protein content and mRNA expression were also significantly decreased, and intracellular p65 protein expression was significantly down-regulated, and IκB protein expression was significantly up-regulated, miR-494 expression was significantly reduced. Intracellular CFTR protein content and mRNA expression were significantly increased in both PDTC group and Qingqi Huatan Pill group. Compared with the PDTC group, the level of TNF-α in the Xiaoqinglong Decoction group was significantly increased (ng/L: 22.77±3.14 vs. 11.09±3.37, P < 0.05), the content and mRNA expression of CFTR and IκB protein expression was significantly decreased [CFTR protein (ng/L): 97.38±6.62 vs. 227.04±19.48, CFTR mRNA (2 -ΔΔCt): 0.99±0.08 vs. 1.21±0.08, IκB/β-actin: 1.69±0.11 vs. 2.00±0.18, all P < 0.05], the level of TNF-α in Qingqi Huatan Pill group was significantly higher (ng/L: 19.08±3.71 vs. 11.09±3.37, P < 0.05). Compared with Xiaoqinglong Decoction group, the protein content and mRNA expression of CFTR and IκB protein expression in Qingqi Huatan Pill group were significantly increased [CFTR protein (ng/L) : 235.01±22.71 vs. 97.38±6.62, CFTR mRNA(2 -ΔΔCt): 1.32±0.15 vs. 0.99±0.08, IκB/β-actin: 1.94±0.16 vs. 1.69±0.11, all P < 0.05]. Conclusions:The effect of Xiaoqinglong Decoctionin improving the hypersecretion of mucus in the airway epithelium may be related to the inhibition of NF-κB/miR-494 inflammatory signal-mediated MUC5AC hypersecretion, while the effect of Qingqi Huatan Pills may be related to the inhibition of NF-κB/miR-494 inflammatory signal-mediated MUC5AC hypersecretion and CFTR dysfunction. Therefore, the difference in the mechanism of the two treatments of airway pathological mucus is mainly in the regulation of CFTR mRNA and protein.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate