BACKGROUND:Disruption of biological rhythms(circadian rhythms)is a typical problem associated with aging.Maintaining the normal function of biological rhythms may be a promising anti-aging strategy.Expression of nuclear factor erthroid 2-related factor 2(Nrf2)is biologically regulated.The glycogen synthase kinase 3(GSK3)system represents a"regulatory valve"that controls subtle oscillations in Nrf2 levels.Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress.However,the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling. OBJECTIVE:To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field. METHODS:The bibliographic method was used to search,review and screen the relevant literature using the keywords of"glycogen synthase kinase 3,nuclear factor erthroid 2-related factor 2,biorhythms and aging"to lay a theoretical foundation for the analysis of the whole paper.Comparative analysis method,through reading and analyzing the obtained literature,was performed to compare the similarities and differences between the literature,thereby providing reasonable theoretical support for the argument.Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION:GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes.GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms.In addition,GSK3/Nrf2 is involved in several metabolic pathways,including those associated with age-related diseases(type 2 diabetes and cancer)and neurodegenerative diseases.

Objective To improve the efficiency and accuracy of videonystagmography calibration test results while enabling effective recognition of saccadic undershoot waveform by developing a dual-stream architecture-based deep learning model. Methods A vestibular function calibration test recognition model with cross-modal feature fusion was constructed by integrating vision transformer (ViT) and a modified ConvNeXt convolutional network. The model utilized trajectory pictures and spatial distribution maps as inputs, employed a multi-task learning framework to classify calibration data, and to directly evaluate undershoot waveform. Results The model showed outstanding performance in assessing calibration compliance. The accuracy, sensitivity, specificity of the model in left side, middle, and right side were all greater than 90%, and AUC values were all greater than 0.99, with 97.66% of optimal accuracy (middle), 98.98% of optimal sensitivity (middle), 96.87% of optimal specificity (right side), and 0.997 of AUC (right side). The model also showed promising performance in undershoot waveform recognition with 87.50% of accuracy, 89.66% of sensitivity, 85.71% of specificity, 86.67% of F1 score, and 0.931 of AUC. Conclusions The proposed method not only significantly enhances the efficiency and accuracy of calibration test results, but also provides a novel solution for undershoot waveform recognition.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

OBJECTIVE To investigate the improvement effect and mechanism of Buyang huanwu tang on idiopathic pulmonary fibrosis （IPF） model rats. METHODS The rats were randomly divided into normal group， model group， pirfenidone group （positive control， 0.162 g/kg）， Buyang huanwu tang low-， medium- and high-dose groups （6.435， 12.87， 25.74 g/kg）， with 6 rats in each group. Except for the normal group， IPF model was established in the remaining groups by intratracheal injection of bleomycin sulfate. On the second day after successful modeling， medication was administered once a day for 28 consecutive days. After the last medication， the appearance and morphology， pathological changes， and fibrosis status of the lung tissues in rats were observed. cyclin-dependent kinase inhibitor 2A （P16）， P21， transforming growth factor-β1 （TGF-β1）， Smad3， Smad7， epidermal growth factor （EGF）， epidermal growth factor receptor （EGFR）， matrix metalloproteinase 12 （MMP-12）， chemokine ligand 2 （CCL2） and interleukin-4 （IL-4） protein expression in lung tissue were all determined. RESULTS Compared with the normal group， the lung tissue of rats in the model group exhibited gray-white color， harder texture， obvious bruising and cysts. Additionally， alveolar septa were significantly thickened， their structural integrity severely compromised， accompanied by pronounced infiltration of inflammatory cells and severe pulmonary fibrosis. Collagen volume fraction， protein expressions of P16， P21， TGF-β1， Smad3， EGF， EGFR and （IL-4） in lung tissue significantly increased （P＜0.05 or P＜0.01）， while Smad7， MMP-12 and CCL2 protein expressions were significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， the appearance， pathological morphology， and fibrosis degree of rat lung tissue in Buyang huanwu tang groups were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Buyang huanwu tang can ameliorate IPF in rats， and its underlying mechanism may be associated with the inhibition of TGF-β1/Smad signaling pathway activity and the attenuation of cellular senescence.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Objective To analyze the relationship between changes of CD80, CD86 and Th1/Th2 cytokines and the severity of coxsackievirus A6 (CVA6) hand-foot-mouth disease (HFMD). Methods Among the 380 children with CVA6 HFMD in the 971th Hospital of the People's Liberation Army Navy and the 94th Hospital of the Joint Logistic Support Force were selected from January 2021 to January 2024. According to the disease severity, the children were divided into common group and severe group. The levels of CD80, CD86 and Th1/Th2 cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4)) were compared between the two groups. The ROC curve was used to analyze the evaluation efficiency of CD80, CD86, IFN gamma, and IL-4 levels on the severity of CVA6 HFMD. Multivariate logistic regression analysis was used to analyze the influencing factors of the severity of CVA6 HFMD. Results The levels of CD80, CD86, IFN-γ and IL-4 in the severe group were higher than those in the common group (P<0.05). The AUCs of CD80, CD86, IFN-γ, IL-4 and their combined detection in evaluating severity of CVA6 HFMD were 0.769, 0.717, 0.756, 0.864, and 0.917, respectively. The AUC value and specificity of combined detection were higher than those of single detection of each index (P<0.05). Multivariate logistic regression analysis indicated that age ≤ 3 years old was a risk factors (P<0.05), while time from onset to diagnosis ≤ 3d, duration of fever ≤ 3d, WB ≤ 12×109/L, low expression of CD80, low expression of IFN-γ, and low expression of IL-4 were protective factors (P<0.05). Conclusion CD80, CD86 and Th1/Th2 cytokines (IFN-γ, IL-4) are related to the severity of CVA6 HFMD. Early monitoring of CD80, CD86, IFN-γ and IL-4 levels in children is conducive to understanding their disease progression and guiding physician treatment.

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

Objective:To investigate the application effect of case-based collaborative learning (CBCL) based on data-information-knowledge-wisdom (DKIW) model in the training of the informatization teaching ability of clinical teachers.Methods:From March to August in 2022, 71 clinical teachers from four grade A tertiary hospitals in Tianjin, China, were selected as subjects and were randomly divided into control group with 35 patients and experimental group with 36 patients using a random number table. The teachers in the control group received blended teaching online and offline, and those in the experimental group received CBCL teaching based on DIKW model. The two groups were compared in terms of theoretical assessment score, informatization teaching demonstration score, and informatization teaching ability score before and after intervention. SPSS 27.0 was used for the t-test and the Mann-Whitney U rank sum test. Results:Compared with the control group after intervention, the experimental group had significantly higher scores of theoretical assessment (83.50±3.11) and informatization teaching demonstration (84.19±1.89) ( P<0.05). After intervention, the control group had significant increases in the total score of informatization teaching ability (74.34±4.08) and the scores of each dimension (15.40±1.19, 19.29±1.62, 28.54±1.67, and 11.11±1.79), and the experimental group also had significant increases in the total score of informatization teaching ability (83.64±5.25) and the scores of each dimension (16.53±1.21, 20.94±1.98, 33.03±2.10, and 13.14±1.48); the experimental group had significantly higher scores than the control group ( P<0.05). Conclusions:The CBCL teaching model based on DIKW model can help to improve the comprehensive informatization teaching ability of clinical teachers.

Objective:To establish a prediction method of diopter based on sequence of ocular biological parameters.Methods:A stratified random cluster sampling method was used to extract the dataset. The dataset consisted of data collected from January 2022 to January 2023 by the Eye & ENT Hospital, Fudan University, from children aged 5 to 13 years in 2 key schools and 2 general schools of Yangpu District, Shanghai. Children’s ocular biological parameters, including sex, age, diopter, axial length, corneal curvature, and anterior chamber depth were collected. The slope of the optimally fitted straight line was calculated using the least squares method. The least square-back propagation (BP) neural network model was established by combining baseline data and the pre-processed rate of the change of ocular biological parameters. The dataset was divided into the training set and the validation set according to the ratio of 8:2 for five-fold cross-validation. The model performance was evaluated by using the mean absolute error (MAE), mean squared error (MSE), root mean square error (RMSE), correlation coefficient R, and coefficient of determination R2. Results:The optimal performances of R2, R, RMSE, MAE, and MSE of the least square-BP neural network model were 0.96, 0.981 9, 0.214 2, 0.139 9 D, 0.045 9, respectively. The regression equation between the predicted value and the true value of the diopter was y=0.97 x+ 0.014 8, R2=0.97, with good correlation. In the internal verification, MAE values of the diopter at three, six, nine, and twelve months of follow-up were 0.110 1, 0.136 0, 0.153 7, and 0.184 8 D, respectively, which achieved clinically acceptable performance (less than 0.25 D). In the external validation, the errors were less than 0.25 D at all ages. Conclusions:A prediction method of diopter based on sequence of ocular biological parameters was successfully developed.