Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

OBJECTIVE To investigate the diagnosis and treatment of small cell neuroendocrine carcinoma(SNEC)of nasal cavity and paranasal sinuses.METHODS The clinical data of 5 patients with SNEC diagnosed at Tianjin People's Hospital and Medical University General Hospital from December 2016 to August 2022 were retrospectively analyzed.There were 4 male patients and 1 female patient.The age range was 40-70 years,with an average age of 55 years.Among them,there were 4 stage ⅣA and 1 stage ⅣC.Two patients underwent surgery plus radiotherapy and chemotherapy,one patient underwent radiotherapy followed by chemotherapy,one patient underwent concurrent radiotherapy and chemotherapy,and one patient refused treatment.The follow-up period was 4-60 months.RESULTS By the end of the follow-up,2 patients died,2 patients relapsed,and 1 patient had no recurrence.CONCLUSION Nasal cavity and paranasal sinus neuroendocrine tumors are rare,and small cell neuroendocrine carcinoma is even rarer.The clinical symptoms are not typical,and it is usually discovered at an advanced stage.The malignancy is high,and it is generally treated with a comprehensive approach that includes radiotherapy and chemotherapy.The treatment effect is poor.

Objective:To investigate the predictive value of maximum tumor diameter and the peripheral blood neutrophil to lymphocyte ratio (NLR) before radiotherapy for the occurrence of esophageal fistula after radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) .Methods:A total of 98 patients with ESCC who underwent radiotherapy in Hefei Cancer Hospital, Chinese Academy of Sciences from February 2017 to February 2021 were selected, and the patients were divided into esophageal fistula group (13 cases) and no esophageal fistula group (85 cases) according to whether esophageal fistula occurred during the follow-up process. The prognostic nutritional index (PNI) , NLR, and systemic inflammatory response index (SIRI) were calculated. Univariate and multivariate logistic regression were used to analyze the influencing factors of esophageal fistula, and the predictive value of each indicator was evaluated by using the receiver operator characteristic (ROC) curve.Results:There were no statistically significant differences in age, smoking history, diabetes mellitus history, gender, concurrent chemotherapy and alcohol history between the esophageal fistula group and the no esophageal fistula group (all P>0.05) , while there were statistically significant differences in PNI ( t=2.24, P=0.041) , NLR ( t=3.75, P=0.001) , SIRI ( t=2.68, P=0.015) . Univariate analysis showed that tumor length ( OR=1.16, 95% CI: 1.01-1.35, P=0.043) , maximum tumor diameter ( OR=1.63, 95% CI: 1.11-2.39, P=0.012) , PNI ( OR=0.83, 95% CI: 0.71-0.98, P=0.023) , NLR ( OR=1.94, 95% CI: 1.20-3.12, P=0.007) and SIRI ( OR=1.82, 95% CI: 1.03-3.24, P=0.041) were related to esophageal fistula. Multivariate analysis showed that maximum tumor diameter ( OR=2.17, 95% CI: 1.02-4.94, P=0.033) and NLR ( OR=2.40, 95% CI: 1.89-6.59, P=0.018) were independent influencing factors for the development of esophageal fistula in patients with ESCC after radiotherapy. ROC curve analysis showed that the area under the curve of maximum tumor diameter before radiotherapy combined with NLR for predicting esophageal fistula in patients with esophageal squamous cell carcinoma after radiotherapy was 0.83 (95% CI: 0.74-0.90) , which was greater than that of maximum tumor diameter before radiotherapy (0.71, 95% CI: 0.63-0.81, Z=1.80, P=0.039) and NLR (0.74, 95% CI: 0.67-0.85, Z=1.64, P=0.046) alone. Conclusions:The maximum tumor diameter before radiotherapy and NLR are closely related to the occurrence of esophageal fistula in ESCC after radiotherapy, and these factors are expected to serve as key predictors of the occurrence of esophageal fistula.

OBJECTIVE To analyze the direct economic burden associated with carbapenem-resistant gram-negative bacteria(CRGNB)infections during hospitalization,and to provide reference for relevant policy formulation.METHODS Basic information including ICU admission,International Classification of Diseases(ICD)codes and CRGNB infection of intensive care unit(ICU)inpatients from Sanya Central Hospital(the Third People's Hospi-tal of Hainan Province)in the southern Hainan region from 2019 to 2023 was collected for risk factor analysis.Propensity matching was performed between the CRGNB infection and non-infection subgroups,and the direct economic differences between the two groups were analyzed.RESULTS A total of 164 373 cases were includ-ed.Multifactor logistic regression analysis revealed that ICD codes F00-F99,G00-G99,I00-I99,J00-J99,L00-L99,N00-N99,P00-P96 and S00-T98,ICU admission,hospital-acquired infection,readmission within 90 days and hospitalization exceeding 7 days were risk factors for CRGNB infection,especially,codes J00-J99(respiratory system diseases)were 7.68 to 17.47 folds higer than codes C00-D48(tumors).In the direct economic analysis of CRGNB infection,different matching results yielded consistent findings.In the 1∶1 matching results,a compari-son of total hospitalization costs(yuan)between different groups showed that the infection group had higher total hospitalization costs than the non-infection group.The costs were as follows:CRGNB group(88 421.40 vs.32 475.56),subgroup with two or more CRGNB types(130 984.02 vs.47 367.27),group with CRGNB and oth-er multidrug-resistant bacteria(103 056.35 vs.37 724.78),CRAB group(98 486.01 vs.36 487.98),and CRE group(26 031.38 vs.17 621.82).CONCLUSIONS The direct economic burden of CRGNB infection is greater than that of the non-infection group.Among them,the direct economic burden of carbapenem-resistant gram-negative bacteria infection,carbapenem-resistant gram-negative bacteria co-infected with other multidrug-resistant bacteria and CRAB infection are the highest.

OBJECTIVE To analyze the direct economic burden associated with carbapenem-resistant gram-negative bacteria(CRGNB)infections during hospitalization,and to provide reference for relevant policy formulation.METHODS Basic information including ICU admission,International Classification of Diseases(ICD)codes and CRGNB infection of intensive care unit(ICU)inpatients from Sanya Central Hospital(the Third People's Hospi-tal of Hainan Province)in the southern Hainan region from 2019 to 2023 was collected for risk factor analysis.Propensity matching was performed between the CRGNB infection and non-infection subgroups,and the direct economic differences between the two groups were analyzed.RESULTS A total of 164 373 cases were includ-ed.Multifactor logistic regression analysis revealed that ICD codes F00-F99,G00-G99,I00-I99,J00-J99,L00-L99,N00-N99,P00-P96 and S00-T98,ICU admission,hospital-acquired infection,readmission within 90 days and hospitalization exceeding 7 days were risk factors for CRGNB infection,especially,codes J00-J99(respiratory system diseases)were 7.68 to 17.47 folds higer than codes C00-D48(tumors).In the direct economic analysis of CRGNB infection,different matching results yielded consistent findings.In the 1∶1 matching results,a compari-son of total hospitalization costs(yuan)between different groups showed that the infection group had higher total hospitalization costs than the non-infection group.The costs were as follows:CRGNB group(88 421.40 vs.32 475.56),subgroup with two or more CRGNB types(130 984.02 vs.47 367.27),group with CRGNB and oth-er multidrug-resistant bacteria(103 056.35 vs.37 724.78),CRAB group(98 486.01 vs.36 487.98),and CRE group(26 031.38 vs.17 621.82).CONCLUSIONS The direct economic burden of CRGNB infection is greater than that of the non-infection group.Among them,the direct economic burden of carbapenem-resistant gram-negative bacteria infection,carbapenem-resistant gram-negative bacteria co-infected with other multidrug-resistant bacteria and CRAB infection are the highest.

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Objective:We investigated the efficacy of furmonertinib in the treatment of de novo small cell lung cancer (SCLC) carrying epi-dermal growth factor receptor (EGFR) sensitive mutations,and elucidated characteristics of the tumor genome,transcriptome,and immune microenvironment. Methods:We analyzed the case of a female patient initially diagnosed with extensive-stage SCLC who had an exon 19 deletion in her EGFR gene. The patient's disease progressed under first-line standard chemotherapy. She thus received the third-generation EGFR-TKI furmonertinib as her second-line treatment,achieving a partial response (PR) and 5-month progression-free survival. After furmon-ertinib treatment failed,a lung tumor biopsy was performed. Genomic,transcriptomic,and tumor immune microenvironment analyses were performed. Results:The histopathological diagnosis of SCLC was confirmed after progression on furmonertinib. Genetic testing of the treated tumor tissues showed that the patient carried an EGFR exon 19 deletion mutation. Transcriptome analysis revealed that the patient's transcriptional molecular subtype was SCLC-A. The tumor mutational burden,PD-L1 TPS,and density of tumor-infiltrating CD4+and CD8+T cells remained at a low level throughout the course of the disease,suggesting that the immune microenvironment was suppressive. Conclu-sions:Extensive-stage SCLC with EGFR-sensitive mutations exhibits a unique phenotype and tumor immune microenvironment. Furmon-ertinib could be an alternative second-line treatment for this type of tumor entity.

AIM:To determine the link between infliximab,adalimumab,vedolizumab,ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application.METHODS:Dis-proportionality analysis and Bayesian analysis were used in data mining to screen the suspected lym-phoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023.The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated.RESULTS:Totally 705 cases of four biological agents associated lymphoma were collected.Four biological agents associated lymphoma appeared to influent more young pa-tients and middle-aged patients than elderly pa-tients(25.11％vs.22.41％vs.12.2％).There were slightly more male than females(42.84％vs.35.60％).Infliximab has the highest reporting odds ratio[ROR3.40,95％CI=(3.03,3.82)],proportional ratio[PRR3.38,95％CI=(3.01,3.79)],information component(IC1.14,IC-2SD=1.02)and empirical Bayes geometric mean(EBGM2.21,EBGM05=2.01).Significant difference in the fatality rate and hospi-talization rate among four biological agents were not found.CONCLUSION:Infliximab showed a strongest lymphoma association than the other three biological agents.Lymphoma risk should be vigilant when using infliximab.