ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.

Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and＞0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8％were male.All patients had 30％-70％coronary stenosis.The consistency rate of QFR and FFR was 78.0％(n=184),and the Person correlation coefficient was 0.557(P＜0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P＜0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P＜0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95％CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95％CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P＜0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

Objective:To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People’s Hospital from January 2010 to March 2024 was conducted.Results:Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma.Conclusion:Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);the above indexes in experimental-H group were significantly different from those in model group(all P＜0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.

As the predominant toxic constituent within the Aconitum genus, Aconitum alkaloids (ATs) exhibit both significant pharmaceutical value and substantial toxicity, have been widely used in traditional Chinese medicine and the realm of contemporary clinical medicine. However, owing to their high toxicity, inappropriate employment of ATs in pharmaceuticals, edibles, and the environment will pose serious threats to human health, inciting a series of toxic incidents. Consequently, it is very important to develop effective analytical methods. This paper presents a comprehensive review of the advancements in research pertaining to the pretreatment and detection methods in common substrates, including high performance liquid chromatography, liquid chromatography-mass spectrometry and rapid detection methods. To explore the specific sources of ATs in actual poisoning cases, the comprehensive traceability strategy based on plant morphology, chemical fingerprint analysis and DNA barcoding technology was discussed, proposing a comprehensive prospect for the development of ATs analysis and traceability, in order to provide guidance for related research within the forensic science domain.