ObjectiveTo conduct a comparative quality analysis of Inulae Flos， fuzz of Inulae Flos and calyx of Inulae Flos， elucidating the scientific connotation of the "removing calyx" process in the traditional processing of Inulae Flos. MethodsInulae Flos decoction pieces were collected， and the fuzz and calyx of Inulae Flos were prepared according to the experiences of old medicine workers. Subsequently， according to the methods under the "Inulae Flos" item in the 2025 edition of the Pharmacopoeia of the People's Republic of China， the appearance characteristics and thin-layer chromatography（TLC） identification of these samples were tested， and the moisture content， total ash content， extract content were also measured. The characteristic fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established by high-performance liquid chromatography（HPLC）， followed by similarity evaluation， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA）. The contents of cryptochlorogenic acid， caffeic acid， 1，3-O-dicaffeoylqunic acid， 1，5-O-dicaffeoylqunic acid， and 1-O-acetyl britannilactone were determined to compare the quality differences of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos. ResultsThe moisture content of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos was all<10%. The determination results of total ash content were as follows：Calyx of Inulae Flos>Inulae Flos>fuzz of Inulae Flos， and the determination results of alcohol-soluble extract content were as follows：Fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. HPLC fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established， and 22 common peaks were identified. The similarity analysis and PCA showed that the overall quality of Inulae Flos and fuzz of Inulae Flos was similar， while the overall quality of calyx of Inulae Flos differed significantly from that of Inulae Flos and fuzz of Inulae Flos. PLS-DA results showed that Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos clustered into distinct groups， indicating significant differences among them. Cryptochlorogenic acid and caffeic acid had relatively high contents in calyx of Inulae Flos， the contents of 1，3-O-dicaffeoylqunic acid and 1，5-O-dicaffeoylqunic acid in Inulae Flos and fuzz of Inulae Flos were higher than those in calyx of Inulae Flos. The order of 1-O-acetyl britannilactone content was determined as follows：fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. ConclusionThe scientific nature of "Removing Calyx" process in the cleansing of Inulae Flos by old medicine workers is demonstrated by the resulting fuzz of Inulae Flos decoction pieces exhibiting enhanced cleanliness and higher content of the index component 1-O-acetyl britannilactone. This study provides a reference basis for further improving and enhancing the processing method and quality control standards of Inulae Flos.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Medical equipment, as an important indicator of smart hospital evaluation, plays a vital role in hospital operations. To ensure the safe and efficient operation of medical equipment, a reasonable performance evaluation system is indispensable. This study introduces a platform based on Internet of Things (IoT) technology that connects medical devices and collects data, achieving standardized and structured data processing, and supporting online operational supervision. Through the Delphi method, a performance evaluation system for large medical equipment is constructed, including 4 primary indicators and 22 secondary indicators. DICOM data acquisition devices are used to achieve functions such as efficiency analysis, benefit analysis, usage evaluation, and decision-making support for medical equipment. The study is still in its early stages, and in the future, it is expected to integrate more types of equipment, achieve rational resource allocation, and significantly impact decision-making for the development of public hospitals.
Internet of Things ; Delphi Technique

Objective To investigate the risk factors for mortality and bleeding complications in extracorporeal membrane oxygenation(ECMO)treated patients and to evaluate the impact of thrombocytopenia severity on the prognosis of ECMO therapy.Methods A total of 153 patients who received ECMO treatment at Peking University Third Hospital between January 2013 and September 2024 were en-rolled in this study.The patients were divided into death group(n=97)and recovery group(n=56)based on their final outcomes.Additionally,the patients were categorized into bleeding group(n=104)and non-bleeding group(n=49)based on the occurrence of bleeding complications during ECMO.Clinical baseline characteristics and extreme laboratory values during ECMO were compared be-tween groups.Logistic regression was used to analyze the risk factors for mortality and bleeding.The patients were further divided,based on the initial platelet(PLT)values on the day of catheter placement and the lowest platelet count during ECMO,into normal group(PLT≥ 100× 109/L),moderate reduction group[PLT=(50～99)× 109/L],and severe reduction group(PLT＜50× 109/L).Kaplan-Meier analysis was used to compare survival rates among these groups.The patients in the moderate and severe reduction groups were further divided into a platelet transfusion group and a non-transfusion group,and the outcomes and complication rates were com-pared.Results The recovery group had a higher proportion of myocarditis,higher minimum values of PLT,Hb,and Fib,and higher initial PLT values,while the maximum values of lactic dehydrogenase(LDH),total bilirubin(T-Bil),prothrombin time(PT),and procalcitonin(PCT)were lower(all P＜0.05)with significant differences.Logistic regression showed that age and maximum PCT were independent risk factors for mortality(OR=1.025 and 1.015 respectively,all P＜0.05).The bleeding group had longer ECMO dura-tions,more plasma transfusions,lower minimum Hb values,and higher maximum values of WBC,neutrophils(Neu),and APTT(all P＜0.05)with statistical differences.The minimum PLT value,maximum WBC value,and maximum APTT value were independent risk factors for bleeding complications(OR=0.986,1.062,and 1.004 respectively,all P＜0.05).Kaplan-Meier analysis showed that the patients in the severe reduction group had lower survival rates,regardless of whether the grouping was based on initial or minimum platelet counts(all P＜0.05).Platelet transfusion improved the mortality in the severe reduction group(P＜0.05)but had no effect on the moderate reduction group.Conclusion Age and peak value of PCT are the risk factors for mortality in ECMO patients,while mini-mum PLT count,peak value of WBC and APTT are the risk factors for bleeding complications.Early intervention for infection and in-flammation during ECMO may improve the outcome of patients.Severe thrombocytopenia during ECMO therapy increased the risk of mortality,and targeted platelet transfusion may improve the survival of these patients.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

Objective To investigate the effect of irisin regulating early B cytokine 3(EBF3)/arachidonic acid-15-lipoxygenase(ALOX15)pathway on the proliferation and migration of lung adenocarcinoma cells.Methods A549 cells were assigned into the irisin solvent group,the irisin group,the sh-NC group,the EBF3 inhibitor(sh-EBF3)group,the irisin+sh-NC group and the irisin+sh-EBF3 group randomly.5-bromo-2-deoxyuracil(EdU)staining and CCK-8 method were applied to detect cell proliferation.5-Scratch experiment was applied to detect the scratch healing rate.2',7'-dichlorofluorescein diacetate(DCFH-DA)staining was applied to detect the level of reactive oxygen species(ROS)in cells.The reagent kit was used to detect glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)in cells.Transmission electron microscopy was applied to observe mitochondrial morphology in A549 cells.QRT-PCR was applied to detect mRNA levels of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 2(MMP-2)and glutathione peroxidase 4(GPX4)in A549 cells.Western blot assay was applied to detect EBF3 and ALOX15 proteins in cells.Results Compared with the irisin solvent group,the mitochondria of A549 cells in the irisin group showed ferroptosis characteristics,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels decreased,and the ROS relative fluorescence intensity,MDA,Fe2+level,and EBF3 and ALOX15 protein levels increased(P＜0.05).Compared with the sh-NC group,the mitochondrial ferroptosis phenomenon of A549 cells was reduced in the sh-EBF3 group,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels increased,and the ROS relative fluorescence intensity,MDA,Fe2+levels and EBF3 and ALOX15 protein levels reduced(P＜0.05).Sh-EBF3 reversed the effect of irisin on ferroptosis,proliferation and migration of A549 cells.Conclusion Irisin may induce ferroptosis in A549 cells and inhibit cell proliferation and migration by activating the EBF3/ALOX15 pathway.