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.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

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 Based on the retrieval and analysis of cases related to the invalidation of drug patents in recent years in China, this paper puts forward relevant suggestions on the operation and management of pharmaceutical enterprises in China. METHODS According to analyzes a total of 503 invalidation request cases filed with the National Intellectual Property Administration from January 1, 2005 to July 12, 2020, analyzed them from the dimensions of the number of cases, involved parties, legal basis, related litigation, etc., which aimed to systematically and comprehensively understand the general situation of patent invalidation cases in the field of medicine in China. RESULTS The number of cases was increasing rapidly year by year, gradually forming a complete closed loop of patent challenges with litigation; the average closing period of administrative litigation after an invalidation case declared was 31.1 months. Judging from the judgment results, the success of patent invalidation rate over 50%. CONCLUSION Pharmaceutical enterprises should pay attention to patent evaluation, analysis and management in the whole process of drug R&D and marketing, improve their independent R&D capabilities and patent management quality.

Objective To observe the value of SimGrid(SG)and S-Enhance(SE)for improving image quality of low-dose X-ray films in children.Methods Data of 344 children in intensive care unit who underwent 410 times bedside X-ray examinations,including 290 times of chest X-ray,51 of abdominal X-ray and 69 of chest and abdominal combined X-ray were enrolled.SG and SE were respectively used for post-processing,and the quality of post-processed images were analyzed.Results Among 410 SG post-processing images,250 images were classified as 2-point,147 as 1-point and 13 as 0-point.SG could significantly improve image quality of children≥1 year and body mass≥10 kg(all P＜0.05),with better ability for displaying bones,trachea,peripheral blood vessels,foreign objects,psoas major muscle and intestinal gas(all P＜0.05).Among 410 SE post-processing images,250 images were classified as 2-point,58 as 1-point and 102 of 0-point.SE could significantly improve image quality of children≥0.5 years and with body mass＞4 kg(all P＜0.05),with better ability for displaying bones,trachea,large blood vessels,peripheral vessels,heart posterior blood vessels and foreign objects(all P＜0.05).Conclusion SG could significantly improve displaying of bones,trachea,peripheral blood vessels,foreign objects,psoas major muscle and intestinal gas in children≥1 year and body mass≥10 kg,while SE could improve displaying of bones,trachea,large blood vessels,peripheral blood vessels,heart posterior blood vessels and foreign objects in children aged≥0.5 years and body mass＞4 kg on low-dose X-ray films.

Objective To observe the reliability of regional 4D flow and whole heart 4D flow cardiac MRI(CMRI)for measuring hemodynamic parameters of left ventricle.Methods Heart ultrasonography and CMRI were prospectively obtained in 31 healthy subjects.Hemodynamic parameters of left ventricle were measured using heart ultrasound,3-chamber 4D flow CMRI(based on inflow and outflow channel of left ventricle)and whole heart 4D flow CMRI,respectively.Intra-class correlation coefficient(ICC)was performed to evaluate the consistencies of the measured left ventricle hemodynamic parameters among the above 3 methods.Results Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,E peak diastolic velocity of mitral valve,supravalvular/subvalvular aortic pressure and aortic valve pressure gradient(all ICC＞0.75),while moderate consistency of A peak diastolic velocity of mitral valve(ICC=0.718)were found between heart ultrasound and 3-chamber 4D flow CMRI.Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,A peak diastolic velocity of mitral valve and supravalvular/subvalvular aortic pressure(all ICC＞0.75),while moderate consistencies of E peak diastolic velocity of mitral valve and aortic valve pressure gradient(ICC=0.600,0.628)were found between heart ultrasound and whole heart 4D flow CMRI.Meanwhile,good consistencies of the above parameters were found between 3-chamber 4D flow CMRI and whole heart 4D flow CMRI(all ICC＞0.75).Conclusion Measuring left ventricular hemodynamic parameters using local regional 4D flow and whole heart 4D flow CMRI were reliable,with good consistency with cardiac ultrasound.

Objective:To construct an explainable artificial intelligence(AI) model of risk characteristics of papillary thyroid carcinoma(PTC), and to explore its value of it combined with clinical features in predicting cervical lymph node metastasis(CLNM) in PTC patients.Methods:From January 2021 to September 2022, 422 patients(422 nodules) with pathologically confirmed PTC underwent thyroidectomy and neck lymph node dissection in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively collected, the patients were randomly divided into training set and test set according to the ratio of 7∶3. Ultrasonographic features highly correlated with PTC risk characteristics were extracted by traditional machine learning method, and an intelligent prediction model with optimal probability of risk characteristics was established. Then, a risk model for predicting CLNM of PTC patients was constructed in combination with clinical features. The diagnostic effectiveness of the model was evaluated by drawing a ROC curve and calculating the area under curve (AUC).Results:In the AI explaineable model of PTC risk characteristics in the test set, the intelligent diagnosis model of calcification based on logistic regression classification showed the highest diagnostic efficiency, with an AUC of 0.87 ( P<0.05). Compared with the probability model of risk characteristic of PTC alone, the comprehensive model combined with clinical characteristics showed higher diagnostic efficiency in predicting CLNM of PTC patients, with AUC of 0.97, diagnostic critical value of 0.15, corresponding accuracy, sensitivity and specificity of 92.65%, 92.76% and 92.54%, respectively (all P<0.05). Conclusions:The explaineble risk characteristics of PTC AI model combined with clinical features can effectively predict the cervical lymph node metastasis of PTC, and then provide effective information for clinical decision-making of PTC patients.

Objective:To understand the molecular characteristics of the mutant strain of polymerase basic protein 2 (PB2) gene of influenza A (H1N1pdm) in Guangdong province, and to explore its specific molecular sites, so as to provide scientific basis for the prevention and control of influenza virus.Methods:Throat swab samples were collected from 2 cases infected with PB2 gene variant strains for virus isolation, and 23 influenza virus strains were selected from Guangdong province for sequencing analysis. The reference sequences and vaccine strain sequences provided by GISAID were used to perform evolutionary analysis on hemagglutinin (HA) and PB2 genes. Virus strain antigen analysis and neuraminidase (NA) inhibition test were carried out. PB2 protein model was constructed and polymerase activity was analyzed.Results:H399N amino acid mutation occurred in the HA gene of PB2-D701N and PB2-A271S variant strains, both of which belonged to the branch of 6B.1A.5a.2a. They belonged to the same big branch and different small branches as the vaccine strain A/Victoria/4897/2022, and they are all vaccine-like strains. In the three-dimensional structure, the mutations of PB2-D701N and PB2-A271S change charge and hydrophobicity.Conclusions:PB2-D701 and A271 were highly conserved, and PB2 mutant strains were not the dominant strains. The PB2 mutant had high antigenicity with the vaccine. The PB2 mutant strain is sensitive to NA inhibitors. The three-dimensional model predicted that PB2-D701N mutation could enhance virulence and affect transmissibility of influenza virus, while PB2-A271S mutation could affect polymerase activity and polymerase complex synthesis of influenza virus.

Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.