Objective To explore the clinical value of artificial intelligence (AI) quantitative parameters in distinguishing pathological grades of stageⅠ invasive adenocarcinoma (IAC). Methods Clinical data of patients with clinical stageⅠ IAC admitted to Yantaishan Hospital Affiliated to Binzhou Medical University from October 2018 to May 2023 were retrospectively analyzed. Based on the 2021 WHO pathological grading criteria for lung adenocarcinoma, IAC was divided into gradeⅠ, grade Ⅱ, and grade Ⅲ. The differences in parameters among the groups were compared, and logistic regression analysis was used to evaluate the predictive efficacy of AI quantitative parameters for grade Ⅲ IAC patients. Parameters were screened using least absolute shrinkage and selection operator (LASSO) regression analysis. Three machine learning models were constructed based on these parameters to predict grade Ⅲ IAC and were internally validated to assess their efficacy. Nomograms were used for visualization. Results A total of 261 IAC patients were included, including 101 males and 160 females, with an average age of 27-88 (61.96±9.17) years. Six patients had dual primary lesions, and different lesions from the same patient were analyzed as independent samples. There were 48 patients of gradeⅠ IAC, 89 patients of grade Ⅱ IAC, and 130 patients of grade Ⅲ IAC. There were statitical differences in the AI quantitive parameters such as consolidation/tumor ratio (CTR), ect among the three goups. (P<0.05). Univariate analysis showed that the differences in all variables except age were statistically significant (P<0.05) between the group gradeⅠ+grade Ⅱand the group grade Ⅲ . Multivariate analysis suggested that CTR and CT standard deviation were independent risk factors for identifying grade Ⅲ IAC, and the two were negatively correlated. Grade Ⅲ IAC exhibited advanced TNM staging, more pathological high-risk factors, higher lymph node metastasis rate, and higher proportion of advanced structure. CTR was positively correlated with the proportion of advanced structures in all patients. This correlation was also observed in grade Ⅲ but not in gradeⅠand grade ⅡIAC. CTR and CT median value were selected by using LASSO regression. Logistic regression, random forest, and XGBoost models were constructed and validated, among which, the XGBoost model demonstrated the best predictive performance. Conclusion Cautious consideration should be given to grade Ⅲ IAC when CTR is higher than 39.48% and CT standard deviation is less than 122.75 HU. The XGBoost model based on combined CTR and CT median value has good predictive efficacy for grade Ⅲ IAC, aiding clinicians in making personalized clinical decisions.

Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN-TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-α was found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-α binding.

Retinal vein occlusion(RVO)is often accompanied by macular edema(ME), which is the main cause of visual impairment in patients. From the perspective of traditional Chinese medicine theory, the key pathogenesis lies in Qi stagnation and blood stasis, as well as internal retention of water and dampness, which is closely related to the dysfunction of internal organs such as liver depression and qi stagnation, spleen failure to function properly, and kidney deficiency with water retention. Although anti-vascular endothelial growth factor(VEGF)therapy has become the first-line treatment option for RVO-ME, some patients show a low response or no response to this therapy, resulting in recurrent ME. According to traditional Chinese medicine, such difficult-to-treat cases are often caused by long-term illness entering the meridians and the interplay of phlegm and blood stasis, or by deficiency of the body's vital energy and the lingering of pathogenic factors. Intervention should be carried out through therapeutic methods such as promoting blood circulation and diuresis, resolving phlegm and unblocking meridians, and strengthening the body's vital energy and eliminating pathogenic factors. At present, the pathogenesis of RVO-ME is not yet fully understood. Modern medicine believes that it may involve multiple factors such as retinal microstructure damage, abnormal blood flow and systemic diseases throughout the body, while traditional Chinese medicine emphasizes the overall connection between local lesions and the imbalance of Qi, blood, Yin and Yang throughout the body. This article systematically reviews the existing research achievements of traditional Chinese and Western medicine on RVO-ME, analyzes its possible high-risk factors, and provides a theoretical basis for formulating individualized treatment plans integrating the advantages of traditional Chinese and Western medicine for such patients.

OBJECTIVE To analyze the relationship between human cytomegalovirus(HCMV)infection and types of carotid atherosclerotic plaques and poor prognosis of patients with ischemic stroke so as to provide bases for im-provement of the prognosis of the patients.METHODS A total of 102 patients with ischemic stroke who were trea-ted in Tengzhou Central People's Hospital form Jun.2022 to Jun.2023 were enrolled in the study,the enrolled pa-tients underwent carotid artery ultrasound examination,and the types of the plaques were analyzed.The peripheral blood HCMV-PP65 antigen was detected by immunofluorescent assay;the tumor necrosis factor-α(TNF-α),in-terleukin-1(IL-1),intercellular adhesion molecule-1(ICAM-1)and vascular endothelial cell adhesion molecule-1(VCAM-1)were detected by enzyme-linked immunosorbent assay,the plasma HCMV DNA viral load was detec-ted by means of real-time fluorescent quantitative polymerase chain reaction.Pearson correlation analysis was per-formed for the association of the HCMV DNA viral load with the levels of TNF-α,IL-1,ICAM-1 and VCAM-1.The incidence rates of adverse events such as intracranial hemorrhage,cerebral hernia,recurrent stroke and death were statistically analyzed within 6 months of follow-up.RESULTS Among the 102 patients,54 were positive for HCMV-PP65 antigen,and 48 were negative for HCMV-PP65 antigen.The percentage of unstable plaque,score of soft plaque,serum TNF-α level,IL-1 level,ICAM-1 level and VCAM-1 level of the positive HCMV-PP65 antigen group were 68.52％,(3.02±0.31)points,(5.03±0.53)μg/L,(5.32±0.55)μg/L,(589.48±59.67)μg/L and(1025.19±5.54)μg/L,respectively,higher than those of the negative HCMV-PP65 antigen group(P＜0.05).The HCMV DNA viral load of the positive HCMV-PP65 antigen group was(4.87±0.51)× 103 copies/ml,higher than(1.42±0.16)× 103 copies/ml of the negative HCMV-PP65 antigen group(P＜0.05).Pearson correlation a-nalysis showed that the levels of TNF-α,IL-1,ICAM-1 and VCAM-1 were positively correlated with the HCMV DNA viral load(P＜0.05).The total incidence of poor prognosis of the positive HCMV-PP65 antigen group was 87.04％,higher than 58.33％of the negative HCMV-PP65 antigen group(P＜0.05).CONCLUSIONS The detec-tion rate of unstable carotid atherosclerotic plaques of the patients positive for HCMV-PP65 antigen is higher than that of the patients negative for HCMV-PP65 antigen.The HCMV infection may aggravate the inflammatory reac-tions and tend to induce poor prognosis.

OBJECTIVE To analyze the relationship between human cytomegalovirus(HCMV)infection and types of carotid atherosclerotic plaques and poor prognosis of patients with ischemic stroke so as to provide bases for im-provement of the prognosis of the patients.METHODS A total of 102 patients with ischemic stroke who were trea-ted in Tengzhou Central People's Hospital form Jun.2022 to Jun.2023 were enrolled in the study,the enrolled pa-tients underwent carotid artery ultrasound examination,and the types of the plaques were analyzed.The peripheral blood HCMV-PP65 antigen was detected by immunofluorescent assay;the tumor necrosis factor-α(TNF-α),in-terleukin-1(IL-1),intercellular adhesion molecule-1(ICAM-1)and vascular endothelial cell adhesion molecule-1(VCAM-1)were detected by enzyme-linked immunosorbent assay,the plasma HCMV DNA viral load was detec-ted by means of real-time fluorescent quantitative polymerase chain reaction.Pearson correlation analysis was per-formed for the association of the HCMV DNA viral load with the levels of TNF-α,IL-1,ICAM-1 and VCAM-1.The incidence rates of adverse events such as intracranial hemorrhage,cerebral hernia,recurrent stroke and death were statistically analyzed within 6 months of follow-up.RESULTS Among the 102 patients,54 were positive for HCMV-PP65 antigen,and 48 were negative for HCMV-PP65 antigen.The percentage of unstable plaque,score of soft plaque,serum TNF-α level,IL-1 level,ICAM-1 level and VCAM-1 level of the positive HCMV-PP65 antigen group were 68.52％,(3.02±0.31)points,(5.03±0.53)μg/L,(5.32±0.55)μg/L,(589.48±59.67)μg/L and(1025.19±5.54)μg/L,respectively,higher than those of the negative HCMV-PP65 antigen group(P＜0.05).The HCMV DNA viral load of the positive HCMV-PP65 antigen group was(4.87±0.51)× 103 copies/ml,higher than(1.42±0.16)× 103 copies/ml of the negative HCMV-PP65 antigen group(P＜0.05).Pearson correlation a-nalysis showed that the levels of TNF-α,IL-1,ICAM-1 and VCAM-1 were positively correlated with the HCMV DNA viral load(P＜0.05).The total incidence of poor prognosis of the positive HCMV-PP65 antigen group was 87.04％,higher than 58.33％of the negative HCMV-PP65 antigen group(P＜0.05).CONCLUSIONS The detec-tion rate of unstable carotid atherosclerotic plaques of the patients positive for HCMV-PP65 antigen is higher than that of the patients negative for HCMV-PP65 antigen.The HCMV infection may aggravate the inflammatory reac-tions and tend to induce poor prognosis.

Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN-TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-α was found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-α binding.

Human mass balance study is a pivotal research in the field of clinical pharmacology, aiming at elucidating the metabolic and excretion pathways of drugs in humans. Currently, human mass balance studies predominantly employ radiolabeling techniques. Recently, both the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) issued related research drafts and guidelines to encourage and guide the pharmaceutical industry to conduct research in compliance with established standards. The selection of radiolabeling sites is crucial for obtaining critical information on drug metabolism. However, in vivo biotransformation may lead to partial disintegration of the molecular structure, thereby resulting in the loss of metabolic product information of the unlabeled moiety. Administering drugs with different radiolabeling sites separately or in combination, or labeling multiple radioactive isotopes within one molecule, can effectively solve this problem. This article reviews relevant technological progress, analyzes radiolabeling strategies, and discusses the application of drugs with multiple radiolabeling sites in human mass balance studies.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell