Objective To analyze the characteristics of viral hepatitis mortality and life loss among residents in Pudong New Area from 2003 to 2023, and to provide a basis for related prevention and control work. Methods Viral hepatitis mortality data were obtained from the Pudong New Area mortality monitoring system. The crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), and standardized potential years of life lost (SPYLL) were calculated to analyze viral hepatitis deaths. The average annual change (AAPC) and annual percentage change (APC) of the mortality rate were calculated by Joinpoint regression analysis to analyze the trend of mortality. Results The CMR and SMR of viral hepatitis among residents in Pudong New Area from 2003 to 2023 were 3.89/100000 and 1.98/100000, respectively. Both CMR and SMR of viral hepatitis showed a decreasing trend over time (CMR:APC=-5.476, t=-13.581, P<0.001; SMR:APC=- 7.624, t= -21.253, P<0.001). The CMR for males was 4.75/100000 and the SMR for males was 2.65/100000; the CMR for females was 3.04/100000 and the SMR for females was 1.32/100000, with a higher mortality rate for males than for females（Z_CME=12.094，P<0.001; Z_SMR=-14.718，P<0.001). Deaths were concentrated in the age groups of 45-64 years old and 65 years old and above, accounting for 91.62% of the total deaths. The PYLL of deaths due to viral hepatitis among residents in Pudong New Area from 2003 to 2023 was 26912 person-years, with a PYLLR of 0.45% and an AYLL of 8.88 years per person. Conclusion The mortality rate of viral hepatitis among the residents of Pudong New Area in 2003-2023 shows a decreasing trend over time. The mortality rate of males is higher than that of females, and the deaths of middle-aged and elderly people account for a large proportion of the total deaths. Chronic hepatitis B is the main cause of death.

Objective To investigate the current distribution of radiotherapy resources in Gansu Province, evaluate the equity of resource allocation, and provide a scientific basis for optimizing regional resource allocation. Methods A questionnaire survey was carried out to assess radiotherapy resources in medical institutions across Gansu Province, China. The equity of radiotherapy resource distribution and associated disparities were assessed using the Gini coefficient, Lorenz curve, and Theil index. Results A total of 23 medical institutions in Gansu Province provided radiotherapy services, comprising 39 radiotherapy devices and 438 professionals, of whom medical physicists accounted for 16.9%. The radiotherapy frequency was 0.47 cases per thousand population. The Gini coefficients for radiotherapy resource distribution ranged from 0.38 to 0.56 by population and from 0.52 to 0.70 by geography. The Theil index for radiotherapy resources ranged from 1.36 to 3.67. Conclusion Radiotherapy resources in Gansu Province were insufficient, and the capacity of radiotherapy service was suboptimal. The equity of radiotherapy resource allocation by geography was worse than that by population. Therefore, it is imperative to address the shortage of radiotherapy resources, strengthen the professional workforce, enhance the capacity radiotherapy service and resource utilization, optimize resource allocation, and promote regional equity in radiotherapy provision in Gansu Province.

Driven by the growing practical need to accelerate drug development and the continuous innovation of trial design in recent years， the number of protocol amendments during clinical trials have gradually increased， and the changed contents have become more flexible and complex， which significantly heightens the difficulty of ethical review on amendments. Against this backdrop， it is of great importance to fully leverage the role and responsibilities of ethics committees， effectively control clinical trial risks， and ensure subject safety. This paper analyzed development trends of protocol amendments in recent years， sorted out requirements for protocol amendments in Chinese regulations and guiding principles， and examined difficulties of amendment ethical review in practical work. Based on these， targeted strategies and recommendations were proposed， namely， strengthening the integration with scientific review， enhancing the formal review， adjusting the scope of review according to approval notifications， and adopting appropriate review methods， with a view to providing insights and references for the management of the amendment ethical review in drug clinical trials.

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.

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.

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.