Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

The chemical constituents from the n-butanol fraction of ethanol extract of safflower (Carthamus tinctorius L.) were isolated and purified using chromatographic process including MCI Gel CHP-20, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC method, and one alkyne and two phenylpropanoid derivants were obtained. Their structures were identified as (5R,E)-tetradecane-12-ene-8,10-diyne-1,5,14-triol (1), (E)-8-O-β-D-glucopyranosyl n-butyl cinnamate (2), and (7S,8S)-7-(4-hydroxy-3-methoxybenzene)-7-butyl-8,9-diol (3) by modern spectroscopy methods (1D NMR, 2D NMR, UV, IR and MS). 1-3 are all new compounds. Compounds 1-3 were screened for their anti-renal fibrosis activities in vitro, and none of them showed obvious effect.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Objective: To investigate the effects of different storage temperatures and durations on the activities of coagulation factor Ⅷ (Factor Ⅷ, FⅧ) and coagulation factor Ⅸ (Factor Ⅸ, FⅨ) after whole blood collection, so as to provide data support for the optimal storage conditions. Methods: A total of 16 mL of whole blood was collected from each of the 20 healthy volunteers at our blood center and aliquoted into 8 sodium citrate anticoagulant tubes. Two tubes were immediately centrifuged for the measurement of FⅧ and FⅨ activity levels. The remaining 6 tubes of whole blood were respectively stored under room temperature and low-temperature conditions. At 2, 4, and 6 h, the whole blood samples were centrifuged and analyzed for FⅧ and FⅨ activity levels. The mean values of the two immediately tested tubes were used as the control group, while other tubes were designated as the experimental groups for comparison. Statistical analysis was performed using SPSS 26.0. Results: The activity of FⅧ in whole blood remained stable after 4 hours of storage at both room temperature and low temperature (116.53±25.95 vs 125.22±27.33, 109.77±23.23 vs 125.22±27.33) (P>0.05 for both). However, by 6 hours, FⅧ activity showed a statistically significant decline compared to the control group (108.65±22.92 vs 125.22±27.33, 100.46±20.19 vs 125.22±27.33) (P<0.05 for both), though the room temperature group results were closer to the control values. The activity of FⅨ in whole blood remained stable after 6 hours of storage under both conditions (97.14±19.48 vs 96.76±19.67, 97.10±17.45 vs 96.76±19.6) (P>0.05 for all comparisons). Conclusion: For whole blood samples after collection, storage at either room temperature or low temperature for up to 4 hours does not compromise the accuracy of test results. When stored for 6 hours, FⅨ activity remains stable, whereas FⅧ activity decreases significantly. Notably, FⅧ activity demonstrates better stability at room temperature than under low-temperature conditions within the 6-hour storage.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Objective: To study the correlation between activated partial thromboplastin time (APTT) mixing test results and the inhibitor titers in hemophilia A inhibitor-positive patients. Methods: In this cross-sectional study, 41 patients with severe hemophilia A and inhibitors (and negative for lupus anticoagulant) were included from the hemophilia clinic of Shandong Blood Center from February 2022 to February 2024. All patients underwent APTT mixing test. The Rosner's index (RI, including the immediate RI and the RI after 2-hour water bath incubation [water bath 2h RI]), the time-dependent difference (Δ value), and the corrected percentage were calculated based on results of APTT mixing test. The median (interquartile range) of the corresponding indexes were calculated, and the ROC curves for identification of high inhibitor titers using the four indexes (the immediate RI, the water bath 2h RI, the Δ value, and the corrected percentage) were plotted, The correlations between APTT mixing test and inhibitor titers for coagulation factor Ⅷ (Factor Ⅷ, FⅧ) were investigated. Results: The median (lower quartile, upper quartile) of immediate RI, water bath 2h RI, Δ-value and corrected percentage for FⅧ inhibitor positive patients were 11.0 (5.4, 29.3)%, 45.0 (25.7, 75.0)%, 26.2 (7.6, 41.8) s, and 82.2 (58.5, 91.6)%, respectively. The median (lower quartile, upper quartile) of the immediate RI, water bath 2h RI, Δ-value and corrected percentage were 25.2 (13.0, 37.5)%, 64.1 (44.6, 72.6)%, 38.0 (14.3, 38.3) s, and 66.5 (50.1, 82.1)% for the high-titer inhibitor group, and 5.2 (4.2, 9.4)%, 17.9 (8.8, 28.0)%, 13.0 (7.6, 25.4) s, and 92.3 (88.0, 94.3)% for the low-titer inhibitor group. The AUCs of the ROC curves for discrimination between high and low titer inhibitor were: 0.9105 for immediate RI, 0.9118 for water bath 2h RI, 0.8873 for correcter percentage, and 0.6532 for Δ-value. Conclusion: High-titer inhibitors can be highly suspected in hemophiliac patients with an immediate RI >10% and a water bath 2h RI >45%, and the presence of low-titer inhibitors is suspected in patients with a 4-second < immediate RI <10% and a 13% < water bath 2h RI <45%.

OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6％)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2％)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5％)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2％)of the 305 patients were classified as poor prognosis,20(6.6％)were classified as good prognosis group,and 22(7.2％)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.

Objective:To investigate the changes of exam scores of retrained peritoneal dialysis (PD) operators (patients, family members, or nannies) with an internal of one year during COVID-19 epidemic and provide basis for targeted training.Methods:It was a cross-sectional survey study. The maintenance PD patients who participated in two trainings with an interval of one year during COVID-19 epidemic from November 1, 2019 to February 28, 2021 in Department of Nephrology in Peking University People's Hospital were enrolled. During COVID-19 epidemic, retraining was extended from once every six months to once a year. The clinical data were collected, the self-designed training exam score table including theoretical knowledge and operational skills assessment was used to investigate the exam scores of two trainings, and the total exam scores and sub-item scores of PD operators before and after one year were compared. Logistic regression analysis was used to analyze the associated factors of the reduction of exam scores.Results:A total of 59 patients were enrolled, with 35 males (59.32%), age of (58.41±14.52) years, and dialysis duration of 42 (12, 84) months. There were 54 patients (91.53%) operating by themselves, 22 operators (37.29%) having college degree or above, and 35 operators (59.32%) having decreased exam scores. The total exam scores were 83.17±7.90 and 80.61±8.20 before and after one year, respectively ( t=2.732, P=0.008). In the six contents of itemized scoring, compared with one year ago, the exam scores of complication treatment ( t=4.928, P<0.001) and self-monitoring ( t=3.222, P=0.002) were significantly decreased. There was no statistically significant difference in the exam scores of environment and hygiene, dialysate replacement operation, exit nursing and diet before and after one year (all P>0.05). The total exam scores in patients with dialysis duration <12 months and 36-60 months after one year were significantly lower than before one year ( t=2.309, P=0.041; t=3.086, P=0.009). There was no statistically significant difference in the exam scores of PD operators with dialysis duration of 12-<36 months and >60 months before and after one year (both P>0.05). Logistic regression analysis showed that dialysis duration was an independent associated factor of exam scores reduction (dialysis duration 36-60 months/>60 months, OR=6.233, 95% CI 1.035-37.529, P=0.046). Conclusions:During COVID-19 epidemic, the reduced frequency of retraining reduces the training exam scores of PD operators, especially in patients with dialysis duration of 36-60 months. The weak points are focused on complication management and self-monitoring. Training should be strengthened for key patients and key contents if regular retraining is not possible due to special circumstances.

Objective:To explore any effect of electroacupuncture (EA) at the Baihui (DU20) and Dazhui (GV14) acupoints on the learning and memory of rats modeling cerebral palsy (CP), and on the miR-126 regulated VEGF/Notch1 pathway.Methods:Fifty-four male Sprague-Dawley rats 7 days old with an average weight of (20±5g) were randomly divided into a sham operation group, a model group, and an electroacupuncture group, each of 18. All except the sham operation group had a model of CP induced using left common carotid artery ligation combined with hypoxia. Twenty-four hours after successful modelling, the EA group received 14 sessions of electroacupuncture at the DU20 and GV14 acupoints, once every other day. On the 29th day, learning and memory ability were evaluated using a Morris Water Maze. The expression of vascular endothelial growth factors (VEGF and VEGFR-2) was detected using immunohistochemical staining. The levels of notch1 and hes1 protein were quantified using western blotting, and the expression of miR-126 RNA was quantified using reverse transcription polymerase chain reactions (RT-qPCRs).Results:Compared with the sham group, there was a significant decrease in the average learning and memory, and the level of miR126 in the model group, but a significant increase in the expression of VEGF and VEGFR-2 and the levels of notch1 and hes1. Significant improvement was observed in all of the measurements of the EA group compared with the model group.Conclusions:Electroacupuncture at the DU20 and GV14 acupoints can improve the ability of learning and memory of rats modeling CP. The mechanism may be related to regulation of the VEGF/notch1 pathway by miR-126 and its promotion of angiogenesis.