ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Objective:To explore Operating Room nurses' behavioral intentions regarding the implementation of isolation techniques in tumor surgery based on the theory of planned behavior (TPB) .Methods:This study was a qualitative research. A purposive sampling method was used to select 14 Operating Room nurses from the Affiliated Hospital of Qingdao University for semi-structured interviews from July to October 2023. An interview outline was developed based on TPB, and the Colaizzi 7-step method was used for data organization and analysis.Results:Among the 14 Operating Room nurses interviewed, two were male and 12 were female, with work experience ranging from one to 36 years and ages between 23 and 59 years. Based on TPB's three dimensions, including behavioral attitude, subjective norm, and perceived behavioral control, eight themes were identified: positive evaluation, negative evaluation, pressure from Operating Room managers and colleagues, pressure from surgeons, pressure from patients, lack of cognitive and skill motivation, work-related stressors as barriers, and analysis of real-world difficulties.Conclusions:Operating Room nurses hold a positive evaluation of implementing isolation techniques in tumor surgery, and their behavioral intention is influenced by nursing managers, surgeons, colleagues, and patients. However, there are also barriers such as a lack of knowledge and skill motivation, multiple work-related stressors, and incomplete institutional processes and standards.

Post-stroke depression,a common complication after stroke,severely affects the physical and mental rehabilitation of patients.Currently,the treatment of depression after stroke has limitations,such as limited efficacy and numerous adverse reactions.Preventing and treating depression after stroke have specific effects;however,the optimal intervention timing and duration remain unclear.Based on the principle of preventive treatment of diseases and the theory that"excessive fire consumes qi"(Huangdi Neijing),this article explores the influence of the stroke etiology and pathogenesis on secondary depression.The article proposes the pathogenesis of post-stroke depression as"wind and fire interacting-excessive fire consuming qi-spirit decline and qi depression,"where fire is the pathological cause,qi is the fundamental pathogenesis,and spirit is the disease manifestation.The disease can be prevented after the occurrence of stroke,but treatment should occur before"excessive fire consumes qi."Clearing fire,preserving the body's normal functions,and reducing fire to protect qi and prevent depression are advisable.After"excessive fire consumes qi,"which results in spirit decline and qi depression,dispersing stagnated liver qi for relieving qi stagnation,nourishing the spirit,and relieving depression to treat it are recommended.This article elaborates on the pathogenesis of post-stroke depression as"fire-qi-spirit,"based on the theory of"excessive fire consumes qi"and"preventing disease from exacerbating."This study proposes reducing fire to protect qi and nourishing the spirit to relieve depression to prevent and treat post-stroke depression,with the aim of providing a novel theoretical basis and practical guidance for preventing and treating post-stroke depression in traditional Chinese medicine.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

The human body is composed of pathways across different dimensions, including systems, organs, cells, and genes. These pathways are interwoven and interact with one another, jointly maintaining the homeostasis of the body. This article discusses the pathways among organs centered on the kidney, pathways between organs and systems, pathways between cells, pathways between cells and genes, as well as pathways among organelles, with the aim of providing clinicians with a multi-level and multi-dimensional perspective for thinking about, exploring, and researching these pathways.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.