ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVES: To develop a risk prediction model for left ventricular adverse remodeling (LVAR) based on cardiac magnetic resonance (CMR) parameters in patients undergoing percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 329 acute STEMI patients undergoing primary PCI at 8 medical centers from January, 2018 to December, 2021 were prospectively enrolled. The parameters of CMR, performed at 7±2 days and 6 months post-PCI, were analyzed using CVI42 software. LVAR was defined as an increase >20% in left ventricular end-diastolic volume or >15% in left ventricular end-systolic volume at 6 months compared to baseline. The patients were randomized into training (n=230) and validation (n=99) sets in a 7∶3 ratio. In the training set, potential predictors were selected using LASSO regression, followed by univariate and multivariate logistic regression to construct a nomogram. Model performance was evaluated using receiver-operating characteristic (ROC) curves, area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: LVAR occurred in 100 patients (30.40%), who had a higher incidence of major adverse cardiovascular events than those without LVAR (58.00% vs 16.16%, P<0.001). Left ventricular global longitudinal strain (LVGLS; OR=0.76, 95% CI: 0.61-0.95, P=0.015) and left atrial active strain (LAAS; OR=0.78, 95% CI: 0.67-0.92, P=0.003) were protective factors for LVAR, while infarct size (IS; OR=1.05, 95% CI: 1.01-1.10, P=0.017) and microvascular obstruction (MVO; OR=1.26, 95% CI: 1.01-1.59, P=0.048) were risk factors for LVAR. The nomogram had an AUC of 0.90 (95% CI: 0.86-0.94) in the training set and an AUC of 0.88 (95% CI: 0.81-0.94) in the validation set. CONCLUSIONS LVGLS, LAAS, IS, and MVO are independent predictors of LVAR in STEMI patients following PCI. The constructed nomogram has a strong predictive ability to provide assistance for management and early intervention of LVAR.
Humans ; Percutaneous Coronary Intervention ; Prospective Studies ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Ventricular Remodeling ; Magnetic Resonance Imaging ; Male ; Female ; Middle Aged ; Risk Factors ; Aged ; Risk Assessment

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule （补肾活血颗粒， BHG） in treating Parkinson's disease （PD） from the perspecitve of dopamine （DA） homeostasis. MethodsSeventy-two mice were randomly divided into blank group， model group， madopar group and BHG low-， medium- and high-dose groups， with 12 mice in each group. Except for the blank group， all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） for 7 consecutive days to induce a PD model. On the day following the injection， BHG low-， medium- and high-dose groups were administered BHG at doses of 1.25， 2.5， and 5.0 mg/（g·d） by oral gavage， respectively， while the madopar group received madopar tablets at dose of 0.093 8 mg/（g·d） by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test， pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase （TH） in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid （DOPAC） in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 （VMAT2） in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase （ERK）， phosphorylated ERK （p-ERK）， cAMP response element-binding protein （CREB）， phosphorylated CREB （p-CREB） and VMAT2 in striatum. ResultsCompared to the blank group， mice in the model group showed a significant decline in total distance and average speed in the open field test， along with an increase in total resting time； in the pole test， both the time required for the mice to turn completely downward （T-turn） and the total time taken to reach the bottom of the pole （T-total） were prolonged； forelimb grip strength was reduced； in the striatum， the mean optical density of TH， the average fluorescence intensity of VMAT2 protein， and DA content all decreased， while the number of striatal neurons was reduced， and the DOPAC/DA ratio was elevated； the levels of p-ERK/ERK， p-CREB/CREB， and VMAT2 in the striatum significantly decreased （P＜0.01）； transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group， mice in the madopar group and BHG low-， medium- and high-dose groups showed significant improvements in all the above indicators （P＜0.05 or P＜0.01）. Compared to madopar group， the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum （P＜0.05）. Compared to the BHG low-dose group， the BHG high-dose group showed increased total distance and mean velocity， decreased total resting time， T-turn， and T-total， as well as enhanced forelimb grip strength； moreover， the average fluorescence intensity of VMAT2 protein， DA content， p-ERK/ERK， p-CREB/CREB， and VMAT2 levels in the striatum were all significantly elevated （P＜0.05 or P＜0.01）. ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To evaluate the forensic application value of used dental floss as a source of bio-logical evidence for individual identification by analyzing the effects of dental floss sample collection methods,DNA extraction methods,preservation conditions,and sampling sites on the success rate of STR typing.Methods Dental floss samples were collected using three techniques:direct cutting,cotton swab wiping,and flocked swab wiping,respectively.DNA was extracted respectively by the Chelex,spin column-based and magnetic bead-based methods.DNA quantification and STR typing were per-formed using the Qubit kit and FGI HumDNA Typing kit(Platinum),respectively.Storage environ-ments(temperature and humidity,ultraviolet radiation)and sampling locations(the floss part,the handle part)on DNA quantity and STR typing were evaluated.Results Through conducting a statisti-cal analysis of three key indicators of average DNA mass concentration,STR locus detection rate,and typing accuracy rate,the direct cutting method demonstrated the highest efficacy,followed by cotton swab wiping mothed,and the flocked swab wiping method had the lowest efficacy.Direct cutting yielded an average DNA mass concentration greater than(4.94±1.87)ng/μL,with STR locus detection and accuracy rates of 100%.Bead-based DNA extraction method produced superior DNA concentration and quality compared to spin column-based and Chelex methods,regardless of whether the sampling technique used.Preservation conditions had a significant impact on the DNA analysis of samples.Par-ticularly,the STR typing accuracy of samples preserved at 55℃/50%RH for 35 days dropped to(81.82±12.31)%,and that of samples exposed to ultraviolet radiation for 12 h dropped to(55.46±34.31)%.DNA concentration from the handle part of dental floss was extremely low,with an STR typing accuracy of only(30.91±27.35)%.Conclusion Using cotton swabs to wipe or directly cutting the thread of dental floss samples,and combining this approach with the magnetic bead method for DNA extraction,can best guarantee the concentration and quality of DNA.In addition,samples should be stored in low-temperature,low-humidity environment,protected from light and ultraviolet radiation.

Objective To investigate the factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.

Objective To evaluate the predictive value of global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)feature-tracking technique for left ventricular remodeling(LVR)after percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week(7±2 days)and 6 months after myocardial infarction to obtain GLS,global radial strain(GRS),global circumferential strain(GCS),ejection fraction(LVEF)and infarct size(IS).The primary endpoint was LVR,defined as an increase of left ventricle end-diastolic volume by≥20%or an increase of left ventricle end-systolic volume by≥15%from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR.Results LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR(n=302),the patients in LVR group exhibited significantly higher GLS and GCS(P<0.001)and lower GRS and LVEF(P<0.001).Logistic regression analysis indicated that both GLS(OR=1.387,95%CI:1.223-1.573;P<0.001)and LVEF(OR=0.951,95%CI:0.914-0.990;P=0.015)were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%,GLS had a sensitivity of 74.3%and a specificity of 71.9%for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR(P=0.146),but was significantly greater than those of other parameters such as GCS,GRS and IS(P<0.05);the AUC of LVEF did not differ significantly from those of the other parameters(P>0.05).Conclusion In patients receiving PCI for STEMI,GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS,GCS,IS and LVEF.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.