ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.

Objective:To compare the efficacy and safety of low-dose and standard-dose radiotherapy (LD-RT vs. SD-RT) in the treatment of oropharyngeal cancer patients with positive human papillomavirus (HPV). Methods:All comparative studies of low-dose versus standard-dose radiotherapy in the treatment of HPV-positive oropharyngeal cancer were searched from PubMed, Web of Science, Cochrane Library, EMbase, Chinese Biomedical Literature Database (CBM), CNKI, Chongqing VIP, and Wanfang databases from January 1, 2000 to February 9, 2023. According to the inclusion and exclusion criteria, the data were strictly screened, and the RevMan 5.4 software was used for meta-analysis.Results:A total of 8 studies were included. The pooled results showed that the overall survival (OS) and progression-free survival (PFS) of patients in the LD-RT group were similar to those in the SD-RT group ( HR=0.83, 95% CI=0.59-1.18, P=0.31; HR=0.97, 95% CI=0.53-1.78, P=0.92), but the rate of percutaneous endoscopic gastrostomy (PEG) insertion was significantly reduced ( RR=0.45, 95% CI=0.28-0.72, P=0.001). Conclusion:LD-RT yields similar efficacy and lower rate of PEG insertion compared with SD-RT in HPV-positive oropharyngeal neoplasm patients.

Objective To analyze blood type unexpected antibody and disease characteristics of inpatients in a hospital,and provide a reference for optimizing precise transfusion schemes and improving clinical transfusion safety.Methods The data of unexpected antibody screening and identification in the General Hospital of Western Theater Command from January 2012 to December 2021 were collected,while information on these patient age,gender,blood transfusion history,pregnancy history and disease diagnosis were also collected.The positive rate,composition ratio and disease characteristics of unexpected antibodies were analyzed.Results The positive rate of unexpected antibody screening was 0.55%(1 736/315 456),in which females were higher than males(0.69%vs 0.44%,χ2=90.107,P＜0.05),patients with a history of blood transfusion or(and)pregnancy were higher than those without a history of blood transfusion or(and)pregnancy(75.69%vs 22.81%,χ2=971.098,P＜0.05),and patients aged 40～80 accounted for 72.93%(1 266/1 736).Patients diseases with unexpected antibody positive accounted for 80.41%(1 396/1 736),mainly including digestive system diseases,immune diseases of blood and hematopoietic organs,tumors,urogenital system diseases,circulatory system diseases,musculoskeletal system and connective tissue diseases.Moreover,91.88%(1 595/1 736)of the patients with anti-screening positive underwent antibody identification,in which the majority of unexpected antibodies were Rh blood group system[41.57%(663/1 595)],Lewis blood group system[11.22%(179/1 595)],and MNS blood group system[6.90%(110/1 595)].Antibody specificity was mainly characterized by anti-E[32.41%(517/1 595)],anti-Lea[10.47%(167/1 595)],and anti-M 6.08%(97/1 595).Other antibodies[35.8%(571/1 595)]were mainly no-detected specific antibodies.Conclusion The screening results of blood type unexpected antibodies and disease type analysis are of great significance for transfusion safety.Blood transfusion department should carry out precise blood transfusion matching with multiple antigens(RhCcDEe,Lea,M)for long-term transfusion patients,women,and patients with pregnancy or blood transfusion history,so as to reduce the incidence of unexpected antibodies and improve transfusion safety.

Objective:To document any effect of a pulsed electromagnetic field (PEMF) on the regulation of neuropeptide Y (NPY) in nucleus pulposus (NP) tissue, NP cell apoptosis and matrix degradation using rats with intervertebral disc degeneration (IDD).Methods:Eighteen Sprague-Dawley rats were randomly divided into a control group, an IDD model group (the model group), and a PEMF group. IDD was induced in both the model and PEMF groups. Right after the modeling, the PEMF group received 14 days of PEMF treatment, while the control group and model group were given no special treatment. Meanwhile, the primary rat nucleus pulposus cells (NPCs) were cultured using Dulbecco′s Modified Eagle Medium at 37℃ and 5% CO 2. When the fusion rate reached 90% after passage, the NPCs were divided into a control group, a TNF-α model group (referred to as model group) and TNF-α + PEMF group (referred to as PEMF group) and treated accordingly. Eight weeks after the modeling, safranin-o/fast green staining was used to assess any pathological morphology changes. The expression of NPY, neuropeptide Y receptor Y2 (NPY2R), bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), collagen type II (Col-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral disc and the cultivated nucleus pulposus cells of the 3 groups were determined. Results:The intervertebral disc cells in the model group were ruptured and folded, with significantly increased polysaccharide and protein components, and significantly increased bone fibers. In the PEMF group the cell boundaries were clearer, with less fibrin fracture and increased cartilage tissue. NPY was expressed in the fibrous annulus and the nucleus pulposus of the intervertebral disc in the model group. The average expression levels of NPY and NPY2R were significantly higher than in the control group and the model group. Compared with the control group, there was a significant increase in the level of Bax and a significant decrease in the expression of Bcl-2 in the model group, and there was a significant decrease in the level of Bax in the PEMF group. Compared with the control group, there was a significant decrease in the Col-II level but a significant increase in the MMP3 protein expression in the model group. The average Col-II mRNA expression was significantly higher in the PEMF group compared with the model group, but the average MMP3 protein expression was significantly less. Those results are consistent with observations in vivo.Conclusion:PEMF may reverse the imbalance of ECM metabolism and delay IDD degeneration by up-regulating the expression of NPY and Bcl-2, as well as blocking the Bax/Bcl-2 signaling pathway to inhibit apoptosis of nucleus pulposus cells.

Objective:To analyze the advantages and disadvantages of online and offline laboratory medicine continuing education and training, and to discuss the future continuing education and training mode under new technology development and new situation.Methods:A questionnaire was administered to the trainees who participated in the 2019 and/or 2020 national continuing medical education project—Clinical Application and Evaluation of New Technologies and Methods of Laboratory Medicine—sponsored by the Department of Laboratory Medicine, West China Hospital, Sichuan University. One hundred and twenty-four questionnaires were completed for the 2019 offline training, and 503 questionnaires were completed for the 2020 online training. The rank sum test, Fisher's exact test, and chi-square test were performed for statistical analysis with the use of SPSS 26.0.Results:The participants in 2020 were significantly younger and the proportion of female participants in 2020 was significantly higher compared with those in 2019. Intermediate titles or above accounted for 66.93% (83/124) in 2019, and intermediate titles or below accounted for 88.67% (446/503) in 2020. The proportion of people from Sichuan Province was significantly higher in 2019. The proportion of trainees from primary institutions was significantly lower in 2019. In 2019, public institutions were mainly tertiary hospitals (74.31%, 81/109), and the majority of participants from private institutions were from third party testing institutions (60.00%, 9/15). In 2020, the percentage of tertiary hospitals in public institutions decreased to 60.99% (258/423), while the percentage of community medical institutions increased to 10.64% (45/423), and 75.00% (60/80) of trainees from private institutions were from tertiary and secondary medical institutions. Trainees with lower educational levels were more likely to appreciate the value of the training course, especially with higher degrees of satisfaction with improvements in theoretical levels and practical skills, and participants from primary institutions believed that the training course could effectively improve their theoretical and practical levels. The number of participants who provided suggestions on laboratory medicine continuing education and training needs in 2019 (83.75%, 67/80) was higher than that in 2020 (48.51%, 244/503). The overall pass rate of post-training assessment in 2020 was 88.52% (424/479).Conclusions:Online and offline training modes have different audience groups and training effects. Online continuing education can provide training opportunities to more primary care personnel and junior and intermediate professionals, which is conducive to improving the basic professional literacy and testing skills of laboratory personnel on the whole. At the same time, the integration of online and offline modes will promote the development of laboratory medicine continuing education.

Acquired cerebral amyloid angiopathy,as a cerebrovascular disease discovered in recent years,mainly spreads through iatrogenic factors.This paper focuses on acquired cerebral amyloid angiopathy and delves into the new applications and profound implications of the"toxins damaging brain collaterals"theory proposed by academician WANG Yongyan in stroke research.Starting from the perspective of"toxins damaging brain collaterals",it comprehensively analyzes the causes and pathological mechanisms of acquired cerebral amyloid angiopathy,emphasizing the importance of external toxins,latent toxins,and turbid toxins in understanding the pathogenesis of the disease.It reveals that"toxins damaging brain collaterals"is the core mechanism of acquired cerebral amyloid angiopathy.On this basis,it proposes a new connotation of"toxins damaging brain collaterals":first,"toxin"includes both internal and external toxins;second,the organic integration of"external wind theory"and"toxins damaging brain collaterals"guides the improvement of theoretical research,clinical treatment,and prevention strategies for stroke,and promotes a deeper understanding of the disease.This approach to understanding acquired cerebral amyloid angiopathy from the perspective of"toxins damaging brain collaterals"not only demonstrates the effective integration of traditional Chinese medicine theory and modern biomedical science,but also provides insights and references for the clinical diagnosis and treatment of the disease.

Objective To analyze the characteristics of blood transfusion consultation cases and establish the consulta-tion route,so as to provide reference for blood transfusion doctors to participate in blood transfusion consultation practice.Methods The cases involved in clinical transfusion consultation in the blood transfusion department of our hospital from 2020 to 2023 were collected from the hospital information system(HIS),and then classified by department and consultation type to summarize the main points of transfusion consultation,formulate transfusion consultation routes,and conduct typical cases analysis.Results There were 315 clinical transfusion consultations from 2020 to 2023,with an increasing trend year by year(26 in 2020,67 in 2021,81 in 2022,141 in 2023).The consultations involved 24 departments,including cardio-vascular medicine 14.0%(44/315),orthopedics 12.7%(40/315),intensive care medicine 8.9%(28/315),general medi-cine 8.3%(28/315),cardiopulmonary disease 6.0%(19/315),etc.There were 8 categories of consultations,including 35.6%(112/315)autologous ozonized blood transfusion,23.8%(75/315)plasma exchange,14.9%(47/315)perioperative mass blood preparation(transfusion),11.4%(36/315)platelet-rich plasma therapy and 6.3%(20/315)autologous blood collection,etc.The clinical blood transfusion consultation route was formulated according to the consultation points.Six pa-tients with various diseases were treated by blood transfusion department.With effective treatment measures taken,all of them improved and were discharged.Conclusion The summary of key points of clinical blood transfusion consultation and formulation of the blood transfusion consultation route by department of blood transfusion are conducive to the implementation of blood transfusion consultation and guarantee the safety of patients.