ObjectiveTo investigate the modifiable areal unit problem （MAUP） in the spatial pattern of Pseudostellaria heterophylla production regions and reveal the impact of statistical scales on the spatial distribution characteristics of this medicinal plant species. MethodsUsing multi-source data （literature records， field surveys， and statistical data）， we systematically analyzed the spatial patterns across three administrative levels （provincial， prefectural， and county scales）. Spatial autocorrelation （Moran's I） analysis， high-low clustering （Getis-Ord General G）， and hot/cold spot analysis （Getis-Ord Gi*） were employed. ResultsThe literature-based analysis showed that the production regions of P. heterophylla presented random distribution on the provincial scale and significant aggregation on the prefectural scale. The field survey data showed that the production regions displayed random distribution on the provincial scale but significant aggregation on both prefectural and county scales. The statistical data revealed that the production regions lacked spatial autocorrelation on the provincial scale but demonstrated significant aggregation on prefectural and county scales. ConclusionMAUP effects have substantive implications for understanding and decision-making in the arrangement of medicinal plant production regions. The county scale proves to be the most sensitive and explanatory level for analyzing the spatial pattern of P. heterophylla production regions， providing a critical foundation for habitat modeling， suitability evaluation， and ecological cultivation planning of medicinal plants.

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Background and aims:Liver fibrosis is a prevalent pathological stage of various chronic liver diseases and has the potential to progress to liver cirrhosis and hepatocellular carcinoma.However,experimental models for in vivo research are limited.Unexpectedly,increased liver inflammation and fibrosis were previously observed in mice treated with aluminum adjuvant(commercial Imject Alum,a mixture of Al(OH)3 and Mg(OH)2).Our study aimed to reveal the pathogenesis and pathological features of Imject Alum-induced liver injury and evaluate its potential as an experimental model of fibrotic liver disease.Methods and materials:C57BL/6J mice were randomly divided into the following four groups:(ⅰ)control group,which received phosphate-buffered saline injections on days 1,12,26,40,and 54;(ⅱ)Imject Alum(Al(OH)3 160 mg/kg)D26 group,which was administered with Imject Alum(Al(OH)3 160 mg/kg)on days 1,12,and 26;(ⅲ)Imject Alum(Al(OH)3 80 mg/kg)D54;and(ⅳ)Imject Alum(Al(OH)3 160 mg/kg)D54 groups,which were treated with 80 mg/kg and 160 mg/kg of Imject Alum(Al(OH)3),respectively,on days 1,12,26,40,and 54.All reagents were delivered by intraperitoneal injection.Serum biochemical pa-rameters,liver pathology,and expression of genes related to inflammation and fibrogenesis were eval-uated.Transcriptome sequencing was performed.The genetic characteristics of the Imject Alum-induced liver lesions in the existing fibrosis model and patients with cirrhosis were determined.Results:Administration of Imject Alum(Al(OH)3 160 mg/kg)at certain points for 54 days led to extensive hepatic inflammation and fibrosis,accompanied by disturbed bile acid metabolism in mice.Moreover,Imject Alum aggravated liver inflammation and injury by activating the pyroptosis-related inflamma-some pathway.Transcriptome analysis revealed that Imject Alum-induced liver lesions had differentially expressed genes that were significantly enriched in pathways related to inflammation,fibrogenesis,and multiple metabolic processes.Moreover,Imject Alum-induced liver lesions exhibited gene signatures similar to those of existing fibrosis models and patients with cirrhosis.Conclusions:Aluminum adjuvant(Imject Alum;Al(OH)3 160 mg/kg)administration at certain points for 54 days resulted in notable liver injury,inflammation,and fibrosis.This model had similar gene expression characteristics with existing fibrosis models and liver samples from patients with cirrhosis.Overall,aluminum adjuvant(Imject Alum)-induced mouse model may be a novel approach for estab-lishing a liver fibrosis animal model.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

Objective:To summarize the electroclinical characteristics of patients with epilepsy with myoclonic absence（EMA）and analyze the relationship with prognosis.Methods:Clinical data of 25 patients with EMA monitored at the pediatric EEG monitoring centers of Peking University People's Hospital and Peking University First Hospital between January 2012 and December 2022 were retrospectively analyzed and divided into three groups according to development before and after the onset of the disease to analyze the electroclinical characteristics and the relationship with prognosis.Results:There were 14 males and 11 females in 25 cases，and the median age of epilepy onset was 48（26，74）months.Sixteen cases in the group with normal development before and after the onset of epilepsy（group A），5 cases in the group with normal development before the onset of epilepsy but retarded development after the onset of epilepsy（group B），and 4 cases in the group with retarded development before and after the onset of epilepsy（group C）.The median age at onset was 62（36，82）months，34（21，66）months，and 26（20，32）months in the three groups，with 3，3，and 4 cases of early onset in each group，respectively.The EEG background activity slowed down in 10 cases，with 6，1 and 3 cases in the three groups，respectively.Interictal EEG was normal in 1 and abnormal in 24 cases，which showed generalized discharges，of which 11 cases showed coexisting focal discharges and generalized discharges.Among the focal discharges，there were cases in all three groups，involving the anterior-posterior，temporal and Rolandic regions.Fifteen cases had myoclonic absence（MA）induced by hyperventilation，with 10 cases in group A，4 cases in group B and 1 case in group C.The most prevalent concomitant seizure was myoclonic seizure（MS），with 9，3 and 2 cases in each group respectively.Statistically significant differences were seen in early onset and refractory EMA among the three groups（both P<0.05）.In further two by two comparisons，the proportion of early onset and drug refractory cases was greater in children in group C than in group A，with statistically significant differences（both P<0.017），and the difference in concomitant MS among the three groups was not statistically significant（ P>0.05）. Conclusions:The MA seizures in children with EMA are sensitive to hyperventilation.The common accompanying seizure is MS.Some children with EMA present with early onset and refractory epilepsy，with a tendency towards developmental epileptic encephalopathy.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder.Primarily involving the skin and central nervous system, it also impacts the heart, lungs, kidneys, and other organs.The vast majority of TSC patients may experience neuropsychiatric symptoms during their lifetime, including behavioral, mental, intellectual, academic, neuropsychological, and psychosocial disorders, which are collectively referred to as TSC-associated neuropsychiatric disorders(TAND).The TAND Checklist is a screening tool designed to identify potential neuropsychiatric disorders by facilitating dialogues between TSC patients, their families, and clinicians.This article focuses on the concept and research history of TAND and the application of the TAND Checklist, contributing to the comprehensive and systematic clinical evaluation and understanding of the prognosis of children with TAND.

Objective To investigate the clinical characteristics and risk factors of the occurrence of hypoxic hepatitis(HH)in children with shock.Methods Clinical data(general situation,clinical situation and prognosis)of 234 children with different types of shock admitted to the pediatrics department of Hainan Women and Children's Medical Center from January 2016 to December 2023 were collected.Serum biochemical indexes on day 1(d1),day 2(d2),day 3(d3),day 5(d5),day 7(d7)of children with shock were collected,including serum alanine aminotransferase(ALT),glutamate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(ALP),albumin(ALB),total bilirubin(TBIL),urea nitrogen(BUN),C reactive protein(CRP),international standardized time(INR)and lactate.And the clinical characteristics and risk factors of the occurrence of HH in children with shock were analyzed.Results A total of 234 cases(150 cases of males)of different types of shock in children were enrolled,ages ranged from 1 month to 16 years old.According to whether developed HH,the children with shock were divided into HH group(32 cases)and non-HH group(202 cases).The total incidence of HH was 13.7%(32/234).Septic shock was the main disease of the occurrence of HH in children with shock,accounting for 65.63%(21/32).According to the prognosis,children with shock combined HH were divided into survival group(17 cases)and death group(15 cases).The case fatality rate of children with shock combined HH was 46.9%.The ALT and AST values in children with shock combined HH were more than 20 times of the upper limits of normal ranges.The peak values of enzymatic indexes in the survival group appeared at the onset time d 1 to d 2,they were close to the normal ranges at the onset time d7,while the enzymatic indexes in the death group were higher than the normal ranges during the whole disease stage.Compared with the survival group,the peak values of ALT,AST,ALP,TBIL,CRP,BUN,and INR in the death group were obviously higher(P<0.05,both).The lowest value of ALB in the death group was lower than that in the survival group(P<0.05).The results of multivariate Logistic regression analysis showed that pediatric critical illness score(PCIS),lactate,multiple organ dysfunction syndrome(MODS),decompensated shock and cardiogenic shock were the risk factors for the occurrence of HH in children with shock(P<0.05 or 0.01),and left ventricular ejection fraction(LVEF)and mean arterial pressure(MAP)were the risk factors of the death of HH in children with shock(P<0.01).Conclusions Children with shock who have the risk factors as decreased PCIS,increased lactate level,MODS,decompensated shock and cardiogenic shock are apt to suffer from HH.Poor prognosis in the chil-dren with shock combined HH is associated with worse condition and lower LVEF.There is a high fatality rate of shock combined HH in children,so that liver function indicators should be closely monitored to early detect HH,and reasonable treatment should be given.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

ObjectiveTo identify potential distribution areas for wild Panax ginseng cultivated under forest in Liaoning province， China， and analyze the ecological factors of spatial stratified heterogeneity affecting its ecological suitability and quality suitability. MethodWild Panax ginseng samples cultivated under forest were collected from 33 cultivation bases in Liaoning province. The Maxent maximum entropy model and ArcGIS were used to delineate the ecological suitability zones. Correlation analysis was performed on seven indicators and 110 ecological factors. Variables with significant correlation （P<0.05） were used to build partial least squares regression analysis models. A comprehensive quality zoning was conducted using the analytic hierarchy process （AHP）. The geographic detector was employed to analyze the interactions among dominant ecological factors of spatial stratified heterogeneity affecting habitat suitability， quality suitability， and the ecological driving factors. ResultVegetation type was the most influential ecological factor for delineating the ecological suitability zones for wild Panax ginseng in Liaoning province. The main ecological suitability areas for wild Panax ginseng cultivated under forest were located in the northeast， east， and southeast regions along the line from Xifeng County to Gaizhou City. The comprehensive quality suitability of wild Panax ginseng cultivated under forest was highest in Kuandian County and Huanren County and gradually decreased to the northwest and southwest. Within the delineated regions， the suitability conditions and comprehensive quality of wild Panax ginseng cultivated under forest were primarily influenced by the interactions between radiation and precipitation factors. The content of the measured samples was significantly higher than the standards in the 2020 edition of the Chinese Pharmacopoeia， indicating the high overall quality of wild Panax ginseng in Liaoning Province. ConclusionAccording to the zoning and prediction results， areas in Fengcheng City， Xiuyan County， Zhuanghe City， Liaoyang County， Tieling County， Xifeng County， Gaizhou City， Haicheng City， and Dashiqiao City showed large potential distribution areas with high quality， making them highly promising for wild Panax ginseng cultivation. However， further experimental verification is required. The zoning results can provide insights for research on habitat suitability and comprehensive quality accumulation of wild Panax ginseng cultivated under forest， as well as guidance for the search for potential cultivation areas and industrial development of wild Panax ginseng in Liaoning Province.