Based on the Delphi method, this study conducted an expert questionnaire survey on the diagnostic criteria of edema in TCM by integrating preliminary literature research, aiming to further standardize the revision of Edema diagnosis in Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine (ZY/T001.1－94). Relevant literature on TCM edema was comprehensively retrieved from CNKI, Wanfang Data, VIP and CBM from 1994 to July 1, 2021. The content extracted from the literature was integrated with the diagnostic criteria outlined in the 1994 Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine to establish the questionnaire item pool; two rounds of Delphi expert surveys were conducted to identify content requiring revisions. Subsequently, the degree of concentration and coordination of the expert opinions were analyzed to determine items for inclusion in the revised draft. Ultimately, the finalized revised diagnostic criteria for edema were developed through expert panel discussions. Results showed expert participation rates of 84.21% and 78.13% in respective survey rounds. The progressive increase in Kendall's coefficient of concordance (Kendall's W=0.169 in Round 1 to Kendall's W=0.368 in Round 2) quantitatively validated enhanced expert consensus (both the degree of concentration and coordination) and systematic alignment of revision proposals for diagnostic items. The study findings demonstrated an urgent need for improving the diagnostic criteria section of the the 1994 Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine, and the proposed revisions would be expected to enhance the applicability and specificity of edema diagnostic standards in clinical practice.

Objective To explore the effect and mechanism of Sechang Zhixie Powder(SCZXS)on mice with acute diarrhea caused by castor oil.Methods The mice were randomly divided into blank control group,model control group,montmorillonite powder group(1.4 g·kg-1),SCZXS-L group(0.9 g·kg-1),SCZXS-M group(1.8 g·kg-1)and SCZXS-H group(3.6 g·kg-1),10 mice in each group.After continuous administration of 7 days,the acute diarrhea model of mice was prepared by oral administration of castor oil(0.01 mL·g-1).The diarrhea of mice was observed within 4 hours of castor oil administration,and the rate of loose stool,degree of loose stool,and diarrhea index were calculated;the levels of DAO,D-LDH,VIP,and SS in the colon were determined by enzyme-linked immunosorbent assay;The morphological changes in the colon tissue of mice were observed after HE staining and the thicknesses of the mucosal and muscular layers of the colon were quantified;AB-PAS staining was performed to observe the effect on mucin in the colon;and the expression of AQP3,Occludin,and ZO-1 in the colon were quantified by immunohistochemistry.Results Compared with the model control group,the rate of loose stool,degree of loose stool,and diarrhea index of the mice in the SCZXS groups tended to decrease,but the difference was not statistically significant.Compared with the model control group,the flat luminal surface of the mice in the SCZXS-M and SCZXS-H group were significantly thickened(P<0.01),and the amount of VIP in the colon was significantly decreased(P<0.05,P<0.01),and that of DAO in the colon was significantly decreased(P<0.01),Occludin and ZO-1 expression were significantly increased(P<0.01),the mucin area ratio was significantly increased(P<0.05)in the SCZXS-M group,and AQP3 expression was significantly increased(P<0.05)in the SCZXS groups.Conclusions SCZXS can improve acute diarrhea induced by castor oil in mice.and its mechanism may be related to the regulation of gastrointestinal hormones and AQP3.In addition,SCZXS improves intestinal damage caused by diarrhea and protects the intestinal barrier.

Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.

In terms of the complexity of the"left"and"right"concepts,these directional terms not only indicate spatial orientation but also embody hierarchical order,official titles,systemic imbalances,and temporal sequences.This study explains the medical theory of"liver is born on the left and lung is hidden on the right,"and reveals its implications for ascending and descending of qi movement pathways,sequential patterns,non-equilibrium states,and the centrality of the middle,thus linking the connotation of this theory and its application.In view of this,the theory of"liver is born on the left and lung is hidden on the right"can be used in the clinical diagnosis and treatment of qi-blood-body fluid and emotional diseases,and guides disease prevention and treatment,as well as enhances the subjective initiative of health maintenance and longevity.This study not only deepens the modern interpretation of the classical theory but also provides novel perspectives for its application in disease prevention and treatment.

Objective:To establish a prediction model for larger for gestational age(LGA)infants in pregnant women with gestational diabetes mellitus(GDM)in order to improve pregnancy outcomes.Methods:A retro-spective analysis was performed on the clinical data of 338 pregnant women with GDM who underwent routine prenatal examinations and were hospitalized for delivery in the First Affiliated Hospital of Nanjing Medical Universi-ty from January 1,2018 to December 31,2023.Pregnant women with complete HbAlc data during pregnancy were divided into a training set of 241 cases and a validation set of 97 cases.Lasso and Logistic regression analysis and variable screening combined with previous clinical experience were used to construct a nomogram model,and its degree of differentiation and calibration were evaluated.Result:①By Lasso regression analysis,age,family histo-ry of type 2 diabetes,body mass index(BMI),gestational weight gain(GWG),fasting blood glucose(FBG),postprandial 1-hour blood glucose(1h PBG),HbAlc,free triiodothyronine(FT3),free thyroxine(FT4)and insulin treatment were important predictors of LGA.②Multivariate Logistic regression analysis showed that GWG and HbAlc were independent risk factors for LGA in pregnant women with GDM(OR＞1,P＜0.05).③Combined with Lasso and Logistic regression analysis,previous literature reports and clinical experience,BMI,GWG,FBG,1h PBG,HbAlc and FT3 were selected as independent variables,and LGA as dependent variable.A nomogram pre-diction model was constructed in the training set,and the C-index of 0.71.ROC curve analysis showed that the AUC values of the training set and the validation set were 0.709 and 0.700,respectively,and the discriminative a-bility of the model was acceptable.The calibration curve of the model was close to the ideal curve,and the clinical decision curve suggested that the model showed a positive net benefit at the threshold of 10％to 50％.Conclu-sion:The predictive model has certain value in predicting the occurrence of LGA in pregnant women with GDM,and provides help for early diagnosis,treatment and clinical intervention of GDM and its complications,in order to improve perinatal and long-term adverse outcomes.

[Purpose]To analyze the incidence and mortality of lung cancer in Zhejiang cancer regi-stration areas in 2021 and trends from 2000 to 2021.[Methods]Using data from Zhejiang cancer registration areas from 2000 to 2021,the crude rate,age-standardized rate by Chinese standard population(ASRC)and the world standard population(ASRW),and composition ratio were calcu-lated to describe the incidence and mortality in 2021.Joinpoint regression was employed to ana-lyze temporal trends over the 22 years,calculating the annual percentage change(APC),average annual percentage change(AAPC),and their 95％confidence intervals(CI).[Results]The crude incidence rate of lung cancer in 2021 was 128.58/105,with an ASRC of 68.74/105,ac-counting for 24.22％of all cancers;the crude mortality rate was 51.55/105,with an ASRC of 21.58/105,constituting 27.98％of all cancer deaths.Both crude incidence rate(AAPC=5.73％,P＜0.001)and ASIRC(AAPC=4.14％,P＜0.001)of lung cancer showed significant increasing trends from 2000 to 2021.The crude mortality rate increased slowly(AAPC=1.76％,P＜0.001),while the ASMRC(AAPC=-0.40％,P=0.035)exhibited a modest decline.The increase in incidence was more pronounced in females than males,though no statistically significant difference was observed in mortality trends.The incidence rates in urban and rural areas showed similar growth trends;the crude mortality rate in rural areas was growing significantly faster than that in urban areas,and the decline in the ASRC was only statistically significant in urban areas.The incidence rate was in-creasing in all age groups.The mortality rate was declining among younger people(＜65 years old).The age group of 15～44 years old demonstrated a greater increase in incidence and a sharper decline in mortality than those aged 45 years old and above.[Conclusion]From 2000 to 2021,Zhejiang Province experienced a marked rise in lung cancer incidence with escalating disease burden.Despite severe population aging,ASRC of mortality declined steadily,reflecting effective prevention and control measures.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.