Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

OBJECTIVE To introduce the characteristics and practice of billable pharmacy service programs in the United States， aiming to provide reference for the development of clinical pharmacy service and the establishment of corresponding billing criteria in China. METHODS By searching the official websites of American Pharmacists Association， American Society of Health- System Pharmacists， Centers for Medicare & Medicaid Services and Centers for Disease Control and Prevention， and the PubMed database， the contents of American billable pharmacy service programs， corresponding service billing criteria， the approaches to being paid as pharmacists and the clinical practice evidence were summarized. RESULTS Current major billable pharmacy service programs implemented in the United States included medication therapy management， outpatient pharmacy service， transition of care management， chronic disease management， annual wellness visits， as well as diabetes self-management training/education. Except for diabetes self-management training/education， which lacked robust data on practice outcomes， all other programs mentioned above were demonstrated to have positive impact on patient outcomes， reducing health care cost and/or generating revenues. The most common approaches for pharmacists to obtain reimbursement were “incident to” billing and using procedure codes. CONCLUSIONS Billable pharmacy practice programs in the United States are achieving progress in service specialization and billing standardization. China can learn from successful cases in the United States while considering its own national context， with the ultimate goal of improving the overall health outcomes of patients， so that pharmacy services can become an important part of the medical service system.

Myocardial infarction （MI） refers to an acute clinical syndrome of myocardial necrosis due to persistent ischemia and hypoxia， resulting from the sharp reduction or interruption of coronary blood flow. Nuclear factor κB （NF-κB） is the key factor in inducing inflammatory response， and it is involved in the production of pro-inflammatory factors and myocardial cell apoptosis. This article systematically describes the molecular regulation mechanism of the NF-κB signaling pathway in MI， and reviews the related research on the prevention and treatment of MI through the regulation of this signaling pathway by active ingredients and compound formulas from traditional Chinese medicine （TCM）. It has been found that active ingredients from TCM， such as ginsenoside Rg3， baicalein， curcumin， tanshinone ⅡA， gambogic acid， as well as compound formulas， including Qili qiangxin capsules， Yiqi huoxue decoction， Lingbao huxin dan， Danhong injection， Baoyuan decoction combined with Taohong siwu decoction， can improve myocardial fibrosis， alleviate inflammatory responses， and inhibit cardiomyocyte apoptosis by suppressing the NF-κB signaling pathway. Thereby， they achieve the goal of preventing and treating MI.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Objective:To investigate and validate the performance of a dosiomics model that utilized 3D dose distribution to forecast radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 3578 patients diagnosed with NPC admitted to Jiangsu Cancer Hospital from January 2011 to December 2021 were retrospectively analyzed. According to the inclusion and exclusion criteria, 97 NPC patients who developed RTLI were assigned into the case group. A 1:1 propensity score matching (PSM) method was used to match 97 NPC patients without RTLI as the control group. Patients were assigned into the training cohort ( n=135) and the validation cohort ( n=59) at a 7:3 ratio by simple random method. Dosiomics features were extracted from the patients' three-dimensional dose distribution maps. Spearman rho and the least absolute shrinkage and selection operator regression were used to select dosiomics features. Clinical features were collected and screened by univariate and multivariate analyses. Eight machine learning classifiers were then trained to build dosiomics models and clinical models, respectively. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to compare the predictive performance of the dosiomics and clinical models. Multivariate analysis was conducted using logistic regression to assess the influencing factors, while comparisons of the ROC curves between two different models were performed using the DeLong test. Results:A total of 1130 dosiomics features were extracted from the three-dimensional dose distribution maps, and 14 features were retained for model building after feature selection. The model based on the support vector machine (SVM) classifier achieved the highest AUC value of 0.977 (95% CI: 0.949-1.000) in the validation cohort, with an AUC of 1.000 (95% CI: 1.000-1.000) in the training cohort. By conducting univariate and multivariate analyses of the patients' clinical features, 2 clinical features were retained to build the clinical model. The model based on the SVM classifier achieved the optimal AUC value of 0.667 (95% CI: 0.523-0.810) in the validation cohort, with an AUC of 0.804 (95% CI: 0.730-0.878) in the training cohort. DeLong test showed that the difference between the dosiomics and clinical models was statistically significant ( P<0.05). Conclusion:The dosiomics model based on 3D dose distribution yields high predictive performance for RTLI in NPC patients after IMRT, which surpasses the clinical feature model, providing a new approach for early clinical prediction of RTLI.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Aim To explore the effect of Nf1 gene silencing on smooth muscle cell proliferation and migration and its possible molecular mechanism.Methods Using mouse aortic vascular smooth muscle cells(MOVAS)as the research object,the efficiency of Nf1 siRNA transfection in MOVAS was verified by RT-qPCR after transfection with Nf1 siRNA.The experiment was divided into control group,siRNA NC group,and Nf1 siRNA group.Ki-67 immunofluores-cence assay was used to detect the proliferation of MOVAS.Scratch assay and Transwell assay were used to evaluate the effect in the migration ability of MOVAS caused by Nf1 gene silencing.Western blot was used to detect the effect of Nf1 gene silencing on the expression levels of MOVAS phenotype marker proteins and the differences in the expression levels of downstream Ras signals extracellular signal-regulated kinase(ERK),p-ERK,protein kinase B(Akt),and p-Akt.Results Compared with the control group,the proliferation ability of MOVAS in the Nf1 siRNA group was significantly in-creased(increased by 33.23%,P<0.05),migration ability was significantly enhanced(scratch assay showed an increase of35.47%,Transwell assay showed an increase of 39.33%,P<0.05 or P<0.01),and the expression of contractile pro-teins smooth muscle 22α(SM22α),α-smooth muscle actin(α-SMA),and calmodulin 1(CNN1)was reduced(de-creased by 18.91%,23.38%and 25.08%,P<0.05 or P<0.01,respectively).The expression of synthetic protein os-teopontin(OPN)was increased(increased by58.70%,P<0.05),and the levels of p-ERK and p-Akt were significantly increased(increased by33.30%and2.42 times,respectively,P<0.05 or P<0.01).Conclusion Nf1 gene silen-cing can significantly enhance the proliferation and migration ability of MOVAS,and transform from a contractile phenotype to a synthetic phenotype.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.