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 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.

Estrogen receptor α36(ERα36),a splice variant of ERα66,is crucial in the pathogenesis,progression,and therapeutic resistance of female estrogen-related tumors(e.g.,breast,cervical,and endometrial cancers)as it uniquely activates non-genomic signaling pathways.This review provides a comprehensive summary of the structural features of ERα36 and its molecular mechanisms in regulating tumor prolif-eration,migration,and drug resistance via membrane-mediated pathways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)and mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK).The interaction between ERα36 and epi-dermal growth factor receptor/human epidermal growth factor receptor2(EGFR/HER2)forms a positive feedback loop that exacerbates ma-lignant transformation.High ERα36 expression is associated with decreased sensitivity to chemotherapy and resistance to tamoxifen.Recent studies have demonstrated that natural compounds and synthetic inhibitors targeting ERα36 can reverse drug resistance and suppress can-cer stem cell activity by blocking non-genomic signaling.This review provides novel insights into overcoming drug resistance and optimizing targeted therapies for female estrogen-related malignancies.

Zika virus(ZIKV)is a mosquito-borne flavivirus associated with neurological complications such as Limbari syndrome in adults and microcephaly in newborns.As there are no drugs or preventive vaccines available to specifically treat ZIKV infection,there is an urgent need to take comprehensive measures to prevent and control ZIKV infection and stop its spread.In this paper,we reviewed the structure and function of ZIKV gene and protein,and summarized the progress in the development of virus-targeting anti-ZIKV drug candidates through high-throughput screening and drug relocation,and summarized the mechanism of action of virus and host cell targeting drug candidates.The research and development trend of small molecule antiviral drugs in the future is prospected,which provides reference for promoting the research and development of new anti-ZIKV drugs.

Objective To quantitatively evaluate structural changes in the TMD disc using magnetic resonance T2 mapping technology at open and closed mouth positions,and assess its significance.Methods 127 newly diagnosed patients with TMD and 51 controls in the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Yunnan University from June 2023 to January 2024 were prospectively collected.All subjects underwent routine TMJ sequence and T2 mapping sequence scans.After scanning,the pseudo-color images were processed,and T2 values of the joint disc(anterior and posterior bands)were measured at open and closed mouth positions to analyze their correlation with TMD disc displacement.Results The T2 values of the posterior zone of the joint disc in both open and closed positions were higher than those in the anterior zone of the joint disc in the case group(P<0.05);for different anterior displacement degrees of the joint disc,T2 values showed a progressive increase from the normal position group to the mild and moderate anterior displacement groups,while the severely displaced group demonstrated a decreasing trend(P<0.01);joint clicking and occlusal abnormalities were independent risk factors for non-reducible anterior joint disc displacement in TMD patients.Conclusion Scans during both mouth-opening and closing positions can be used to assess joint disc injury in TMD;T2 mapping technology can quantitatively and sensitively reflect changes in the biochemical composition of joint disc microstructure.

This study was aimed atanalyzing the epidemic characteristics of dengue fever in Ruili City atthe China-Myanmar bor-der in late 2023,to provide evidence for local dengue fever prevention and control measures.Adult Aedes mosquitoes were collected from Ruili City with a backpack type mosquito sucking machine in October of 2023.Serum samples frompatients with suspected den-gue were collected in acutephase,in November of 2023.Detection ofdengue virus(DENV)nucleic acids in Aedesmosquitoes and acute phase serum samples from suspected dengue fever patients using reverse transcription-polymerase chain reaction,and nucleic acid positive samples were inoculated into Vero cells for viral culture.After three consecutive blind passage,samples with cytopathic effect(CPE)were collected for be sequencingand analysisof genetic and evolutionary information.Dengue case characteristics were analyzed through descriptive epidemiological methods.Among the 109 cases of dengue fever,the ratio of males to females was 1.27∶1.The youngest patient was 1 year old,the oldest patient was 84 years old,the age group of 20～59 years accounted for 73.39%,and the major-ity of occupations were freelancer(40.37%).A total of 827 female Aedes albopictus and 312 Aedes aegypti were collected,all of which tested negative for DENV nucleic acid.109 serum samples tested positive for DENV nucleic acid,including 49 DENV-1 and 60 DENV-2.Moreover,five DENV-1 and nine DENV-2 samples were obtainedthrough third-generation blind passaging with CPE.The E gene sequences of these five DENV-1 strains were detected,all were found to belong to DENV-1 genotype I,and had same evolu-tionary branch as the 2023 Guangzhou,China(PP563911),the 2019 Myanmar(MW793710),and 2019 Attapeu,Laos(MW559046).The nucleotide and amino acid sequence similarityamong the five DENV-1 genotype was 99.4%-99.9%and 99.8%-100.0%.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.5%-100.0%,99.4%-99.6%and 99.3%-99.5%,respec-tively,and amino acid similarity was 99.8%-100.0%.Nine DENV-2 E gene sequences were of Asian genotype I and belonged to the same evolutionary branch as the 2018 Myanmar(MW788982),2019 Hangzhou(OP684212)and 2019 Ruili(OQ928150).The nucleotide and amino acid similarities of the nine samples were 99.5%-100.0%and 99.8%-100.0%,respectively.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.7%-100.0%,99.3%-99.7%and 99.3%-99.7%,respectively,and the amino acid similarity was 99.8%-100%,99.8%-100.0%and 99.4%-99.6%,respectively.Two dengue vectors,Aedes albopictus and Aedes aegypti,were present in Ruili city,and the dengue outbreak was caused primarily by DENV-1 genotype I and DENV-2 Asian genotype I in later 2023.The sources of DENV-1 were probably the same as those of DENV-1 with Guangzhou(2023),and the sources of DENV-2 were probably from Myanmar.Dengue cases were found primarilyin the 20-59 year age group and freelancers,thus suggesting that relevant local departments should strengthen surveillance of dengue imported case and vector.

BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.

Objective:To investigate the prevalence of chronic endometritis(CE)in patients with repeated implantation failure(RIF),and the correlation between diagnostic indexes of CE and classification of peripheral blood immune cells.Methods:A total of 64 patients with RIF who visited Outpatient of Hebei Reproductive Health Hospital from January 2020 to December 2021 were retrospec-tively analyzed.General information of patients,results of hysteroscopy and endometrial immunohistochemistry in the mid luteal phase,the number and percentage of NK cells,Th1 cells,Th2 cells,Th17 cells and Treg cells in peripheral blood,and Th1/Th2,Th17/Treg were collected,and the pregnancy outcome of retransplantation was followed up.To evaluate the consistency of hysteroscopy and endometrial immunohistochemistry CD138 in diagnosis of CE in RIF patients,to analyze whether chronic inflammation of endome-trium was related to classification of peripheral blood immune cells,and to analyze the pregnancy outcome of patients with RIF diag-nosed with CE after retransplantation.Results:Prevalence of CE in RIF patients detected by hysteroscopy was 53.12%,which was sig-nificantly higher than that detected by endometrial immunohistochemistry CD138(25.00%,P<0.05).There was no significant differ-ence in the number and percentage of immune cells in peripheral blood between CE and non CE patients.After antibiotic treatment,the 12-week continuous pregnancy rate and live birth rate in the CD138 positive group were higher than those in negative group,with a statistically significant difference(P<0.05).Conclusion:The combination of hysteroscopy and endometrial CD138 immunohistochem-istry at the right time for RIF patients is beneficial to improve their pregnancy rate and pregnancy outcome.The infiltration of endome-trial plasma cells does not affect the classification of peripheral blood immune cells.

Objective This study aims to investigate controversial cases of forensic clinical re-identification of fractures,exploring the characteristics,causes,and countermeasures related to identification errors in primary bone injuries,complications,and subsequent changes.The goal is to provide identification strategies for similar cases regarding the collection of identification materials,timing,and examination method selection,ultimately establishing a paradigm for such identifications.Methods A total of 103 cases of clinical re-identification of fractures accepted by the West China Forensic Identification Center from 2020 to 2024 were collected,and the data from initial identifications and re-identifications were retrospectively analyzed.Results Male cases accounted for 69.90%of the re-identifications,with disability grade(67.96%)and injury degree(30.10%)being the primary concerns.Individual requests represented a high proportion(92.86%)in the initial assessment of disability levels,while unit or joint requests dominated the re-assessment(92.86%).The agreement rates for disability grade and injury degree were 55.26%and 59.38%,respectively.The reassessment of disability grades primarily involved fractures of limb long bones,spine,and ribs,with 75.53%of opinions resulting in downgraded disability levels.Rib,orbital,and nasal bone fractures were the main focus in injury degree reassessments,with 84.62%of opinions indicating aggravated injuries.The consistency rates for fracture identification in disability grade assessments was 92.21%,while rates for injury degree and sequelae were 65.63%and 48.94%,respectively.Inconsistencies in identifying damage facts—including the presence of fractures,distinguishing between fresh and old fractures,and determining the nature of fractures and sequelae—were primarily noted in rib,orbital,and nasal bone fractures.The utilization rate of CT metadata in initial evaluations(25.00%)was significantly lower than in re-evaluations(95.00%).The identification time for joint mobility dysfunction after fracture in re-identifications was significantly longer than in initial identifications(P=0.0002),and the identification time for cases with agreement was significantly shorter than for cases with disagreement(P=0.036).Conclusion Image data type and identification timing are critical factors that may influence the accuracy and consistency of forensic clinical identification of bone injuries.When necessary,dynamic CT metadata in conjunction with image post-processing technology can be routinely employed to identify fractures of the ribs,orbital bones,or nasal bones,thereby reducing the risk of misidentification.

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.