ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

This paper summarizes the progress of theoretical research and practice of One Health in China,and discusses the paradigm of One Health governance to improve the prevention and control of infectious diseases in China and the world,and provide an example for the improvement of the public health system.In particular,China has long history to apply the concept of One Health in the national schistosomiasis control programmes and patriotic health campaigns,which were not only focusing on human health,but also emphasizing the sustainable development of animal health and ecological environment.At the same time,the application of tools such as system dynamics model,eDNA technology,One Health economic assessment and global One Health index(GOHI)in the field of disease control and environmental health provides technical support for the concept of One Health.Despite the challenges of practical application of these tools,the One Health concept will play a greater role in providing sustainable solutions for human-animal-environmental health by strengthening interdisciplinary collaboration,improving standardization protocols and promoting inter-national cooperation.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective:To explore the association between perceived social support,TMEM161B gene rs768705 polymorphism,and their interaction with incidence of depressive symptoms in the freshmen.Methods:A total of 9928 freshmen from two medical universities were investigated at baseline and follow-up two years later during 2018-2020 by cluster sampling.A self-report demographic characteristics questionnaire was used to collect information of general demographic characteristics.Perceived Social Support Scale,Beck Depression Inventory,Beck Anxiety Inventory and Adolescent Self-Rating Life Events Check List were used to measure the level of perceived social support,depressive symptoms,anxiety symptoms and the number of negative life events of individuals.Blood sam-ples were collected and typed for DNA by professionals.Results:Family support and other support were all nega-tively associated with depressive symptoms in the freshmen(OR=0.96,95％CI:0.93-0.99;OR=0.94,95％CI:0.91-0.98).There was no correlation between friend support and depressive symptoms in the freshmen(OR=0.99,95％CI:0.95-1.02).TMEM161B gene rs768705 polymorphism(AG)was positively associated with de-pressive symptoms in the freshmen(OR=1.58,95％CI:1.12-2.23).The interactions of friend support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.26)and other support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.25)had significant effects on the incidence of depressive symptoms in the females and no significant effect in the males.Conclusion:The perceived social support,TMEM161B gene rs768705 polymorphism and their interaction are associated with influence of de-pressive symptoms,and have sex difference in the freshmen.

Objective:To explore the risk factors of suicidal ideation in community residents in Shandong province,China,and to establish a prediction model and a nomogram for the risk of suicidal ideation.Methods:To-tally 11 087 community residents in Jining City,Zoucheng City,and Weifang City,Shandong Province,were recrui-ted as the study subjects.The general information questionnaire,Composite International Diagnostic Interview-3.0,General Anxiety Disorder-7,were used to collect demographic information,mental health status,family information,and lifestyle using a computer-assisted interview system to conduct face-to-face interview.LASSO regression and binary logistic regression analyses were used to develop a nomogram model of the risk of suicidal ideation.Results:Young people,female,smoking,non-new town residents,no physical exercise,difficulty approaching people,anxiety symptoms and depression were effective predictors of suicidal ideation.The area under the curve(AUC)of the training set(AUC)was 0.89(95％CI:0.85-0.93)and AUC of the validation set(AUC)was 0.83(95％CI:0.75-0.92).Conclusion:The nomogram prediction model constructed in this study on suicidal ideation in com-munity residents has a high degree of differentiation and accuracy.It could be used to screen people at high risk of suicide and provide intervention to suicidal ideation in community residents.

Objective To compare imaging quality and semi-quantitative parameters of 18F-FDG whole-body images obtained with domestic NeuWise and Philips Ingenuity TF PET/CT scanners.Methods Thirty-four patients who underwent 18F-FDG whole-body scanning using NeuWise and Philips Ingenuity TF PET/CT systems respectively on the same day were enrolled.The imaging quality and semi-quantitative parameters of 2 kind images,also the mean standard uptake value(SUVmean)of normal tissue,the maximum standard uptake value(SUVmax),peak standard uptake value(SUVpeak),SUVmean of lesions,total lesion glycolysis(TLG)and metabolic tumor volume(MTV)were compared.Results No significant difference of imaging quality nor semi-quantitative parameters of lesions(all P＞0.05),while significant differences of SUVmean of aortic arch,liver,lumbar vertebra and spinal cord were found between 2 kind images(all P＜0.05).Strong correlations of SUVmax,SUVmean,MTV and TLG of lesions(r,=0.734-0.890,P＜0.001),and high correlation of SUVpeak(rs=0.919,P＜0.001)were found between 2 kind images.The consistency of SUVmax,SUVpeak,SUVmean,TLG and MTV at the lesion site between 2 kind images were very good to extremely good(ICC=0.891-0.986,all P＜0.001),and the differences of all above semi-quantitative parameters were within 95％confidence interval.Conclusion Imaging quality of 18F-FDG whole-body images obtained with domestic NeuWise and Philips Ingenuity TF PET/CT scanners could meet the requirements of clinical diagnosis and treatment,and semi-quantitative parameters obtained based on both images had good consistencies.

Aim To investigate the effects of SAHA on the expression of P-gp and the pharmacokinetic pa-rameters of its substrate phenytoin sodium in rats under hypoxic environments.Methods Wistar rats were randomly divided into the normioxic group,the hypoxic model group,and the low-,medium-and high-dose vorinostat(SAHA)groups.Liver tissues were col-lected,and the expression levels of P-gp and HDAC5 were detected by Real-time PCR and Western blot.The morphological changes of liver tissues were ob-served by HE staining.Following intragastric adminis-tration of 50 mg·kg-1 phenytoin sodium to each group,blood samples were collected,and the plasma concentration of phenytoin sodium was determined u-sing UFLC-MS/MS to calculate pharmacokinetic pa-rameters.Results Compared with the normoxic group,the expression of HDAC5 in the liver tissues of hypoxia model rats increased,while the expression of P-gp decreased.After SAHA treatment,HDAC5 expression decreased,and P-gp expression increased.Among the SAHA groups,the medium-dose group showed the most significant effect,and HE staining re-sults indicated that this concentration did not cause damage to rat liver tissues.Compared with the normox-ic group,the AUC,Cmax,and T1/2 of phenytoin sodium in hypoxia model rats were significantly raised.After administration of the medium dose of SAHA,the AUC,Cmax,MRT,and T1/2 were significantly reduced,while CLZ/r was significantly increased.Conclusions Un-der hypoxic environments,the expression of P-gp in rat liver tissue is significantly downregulated,leading to increased systemic exposure of phenytoin,reduced clearance,and consequently elevated blood concentra-tions,raising the risk of central nervous system toxici-ty.In contrast,SAHA suppresses HDAC5 expression,thereby activating P-gp transcription and enhancing its efflux function.This results in decreased systemic ex-posure and improved clearance of phenytoin,signifi-cantly reducing drug accumulation in body and ulti-mately lowering the risk of adverse effects.

Objective To analyze the CT manifestations of high altitude pulmonary edema(HAPE)to provide radiological evidence for its early and accurate diagnosis.Methods Totally 200 HAPE patients clinically confirmed at some hospital from April 2021 to April 2024 were enrolled into a study group,and 56 individuals undergoing health examinations at the hospital's physical examination center between January and June 2023 were included into a control group.Examinations were carried out with a United Imaging uCT528 40-slice spiral CT scanner.The patients in the study group were observed in terms of HAPE staging,the extent of pulmonary involvement,CT manifestations of different stages including location,distribution,density and morphology of pulmonary lesion.The diameters of the main pulmonary arteries and ascending aortas of the subjects in the two groups were measured,and the ratios of the two diameters were calculated.SPSS 25.0 software was used for statistical analysis.Results In the study group,there were 26 cases(13.0%)at early stage,105 ones at progression stage(52.5%),32 ones at critical outbreak stage(16.0%)and 37 ones at resolution and absorption stage(18.5%),and there were 35.5%with unilateral lung involvement and 64.5%with bilateral involvement.At early stage,HAPE chest CT manifestations included increased and thickened bilateral bronchovascular bundles,widened main pulmonary artery lumen and faint ground-glass opacity in lungs;at progression stage,HAPE chest CT manifestations revealed multiple cloud-like or patchy areas of increased density within lungs;at critical outbreak stage,CT scanning indicated diffuse patchy opacities and consolidation in lungs,white lung-like changes could be found in some severe cases,and bronchial air signs were shown within affected segments in some ones with severer signs in the right lung than in the left lung;at resolution and absorption stage the CT manifestations were similar to those at early stage,with lesions completely resolving after treatment.The study group had the diameters of the main pulmonary arteries greater while the diameters of the ascending aortas less than those of the control group,and the ratios of the diameters of the two diameters in the study group were higher than those in the control group,with the differences being statistically significant(all P<0.05).Conclusion Chest CT is an important examination method for the early diagnosis of HAPE and clarification of its clinical staging,which directly reflects the pulmonary pathological changes in HAPE patients and helps doctors fully understand the disease progression.

Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.