OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Transfusion technicians constitute a core workforce in safeguarding blood safety, and the quality of their standardized training directly affects the operational efficiency of the blood services. At present, training programs for transfusion technicians across China have been developed in a diversified manner. Positive progress has been achieved in integrated theoretical and practical training, on-the-job faculty development, and regional collaborative training models. However, persistent challenges remain, including fragmented training providers, inconsistent training standards, limited coverage, and a disconnect between training and workforce utilization. Based on a review of current standardized training practice, this article systematically analyzes the structural challenges confronting current standardized training, and further proposes a framework for building a comprehensive training system, covering the definition and core components of standardized training, targeted improvement strategies and key assessment indicators. The study aims to facilitate the transformation of training for blood transfusion technicians in blood services from a project-based approach to an institutionalized model, and from fragmented implementation to a systematic framework.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Based on the concept of strategic purchasing,it explores the underlying logic of medical insurance payment for hospital weight management services,including enhancing the cost-effectiveness of health investment,motivating hospitals to improve the quality and efficiency of weight management services,and promoting the supply-side reform of weight management services.By drawing on international experience in medical insurance payment for weight management services and analyzing the current practices of Chinese medical insurance systems,it is found China faces challenges in promoting hospital weight management services,such as incoordination between weight management policy advocacy and medical insurance funding,conflicting DRG grouping schemes,and inadequate insurance coverage.To address these issues,it proposes strategies including:improve the top-level design of medical insurance payment for hospital weight management services,give full play to the incentive role of medical insurance payment on hospitals and individuals,build a diversified medical insurance support system for weight management services,optimize the practice path of medical insurance payment for hospital weight management services,and help promote the Healthy China strategy.

Objective To study how lipid bilayer fluidity modulates the interaction between β1 integrin and CD40L,as well as the formation of CD40L-mediated tumor cell contact interfaces.Methods Supported lipid bilayers(SLB)with different fluidities were prepared through adjusting the 1,2-dioleoyl-sn-glycero-3-[N-(5-amino-l-carboxypentyl)iminodiacetic acid]succinyl nickel salt(DGS-NTA)content.The functionalization of lipid bilayers was achieved by anchoring fluorescently labeled CD40L molecules onto the membrane surface.The contact interface formation of PC9 cells on the functionalized lipid bilayers was observed through confocal fluorescence imaging and fluorescence recovery after photobleaching(FRAP)experiments,and data of two dimensional(2D)reaction kinetics of β1 integrin and CD40L were extracted from Zhu-Golan plots.Results The diffusion coefficient of molecules in lipid bilayer was negatively correlated with DGS-NTA content.High fluidity of lipid bilayer promoted CD40L accumulation at cell contact interface and expanded the cell contact area.The 2D dissociation constants(2D Kd)of β1 integrin-CD40L complexes were approximately 13,31 and 65 molecules/μm2 for the three lipid bilayers with high,moderate and low fluidities,respectively.Conclusions High fluidity of lipid bilayers significantly facilitates diffusion and aggregation of CD40L to the cell contact interface,thus enhancing β1 integrin-CD40L interaction and the stability of cell contact interfaces.

Objective This study aimed to investigate how β-glucosidase(GBA)knockdown affects malignant progression in cisplatin(DDP)-resistant ovarian cancer(OC)cells and the role of the EGFR signaling pathway.Methods The A2780/DDP cells were categorized into four groups,with one of them serving as blank control(Con)group,si-NC group(transfected with negative control si-NC),si-GBA group(transfected with si-GBA),and NSC 228155 group(transfected with si-GBA and treated with 2 μmol/L NSC 228155).The protein expression levels of GBA,E-cadherin,N-cadherin,Vimentin,EGFR,p38 mitogen-activated protein kinase(p38 MAPK),phospho(p)-p38 MAPK,extracellular regulated protein kinase(ERK)and p-ERK were detected through Western blot.The relative expression of GBA was evaluated through reverse transcription quantitative polymerase chain reaction.The proliferation activity,migration,and invasion potential were evaluated using cell counting kit-8(CCK-8),plate clone formation,cell scratch healing,and Transwell migration assays.Thirty-six nude mice were divided into six groups(six mice per group):blank control(injected with normal saline),blank control+DDP(treated with DDP),negative control(injected with A2780/DDP cell suspension transfected with si-NC),negative control+DDP(injected with A2780/DDP cell suspension transfected with si-NC and treated with DDP),knockdown(injected with A2780/DDP cell suspension transfected with si-GBA),and knockdown+DDP groups(injected with A2780/DDP cell suspension transfected with si-GBA and treated with DDP).The tumor volume and weight of nude mice were evaluated.Results The relative protein and mRNA expression levels of GBA were significantly higher in the A2780/DDP group than in the A2780 group(P＜0.05).Compared with estimates in the Con and si-NC groups,the proliferation activity,number of cloned cells,scratch repair rate,and number of transmembrane cells in the si-GBA group were significantly lower(P＜0.05).The abundance of E-cadherin expression exhibited a notable elevation(P＜0.05),and expression levels of Vimentin,N-cadherin,and EGFR as well as the p-p38 MAPK/p38 MAPK and p-ERK/ERK ratios were significantly decreased(P＜0.05).The proliferation activity,number of cloned cells,scratch repair rate,and the count of transmembrane cells and the expression level of E-cadherin in the NSC 228155 group were markedly higher and lower,respectively,than those in the si-GBA group(P＜0.05),and the expression levels of Vimentin,N-cadherin,and EGFR as well as the ratios of p-p38 MAPK/p38 MAPK and p-ERK/ERK were significantly increased(P＜0.05).In the nude mouse xenograft study,the tumor size and mass in the blank control+DDP group were notably smaller and lighter,respectively,compared to those in the blank control group(P＜0.05).The tumor volume and weight were significantly lower in the negative control+DDP group than in the negative control group(P＜0.05),significantly lower in the knockdown+DDP group than in the knockdown group(P＜0.05),moreover,they were markedly reduced in the knockdown group in comparison to both the blank control and negative control groups(P＜0.05).Compared with those in the blank control+DDP and negative control+DDP groups,the tumor volume and weight in the knockdown+DDP group were significantly reduced(P＜0.05).Conclusions GBA knockdown suppresses the proliferation,migration,and invasion of DDP-resistant OC cells significantly as well as the growth of subcutaneous xenografts derived from A2780/DDP cells in nude mice.These effects may be mediated through the inhibition of the EGFR/MAPK/ERK signaling pathway.

Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.

Objective:To evaluate the clinical status of long-term oral anticoagulant management in patients with atrial fibrillation, and to analyze the obstacles and promoting factors in the implementation of evidence, so as to provide evidence for clinical transformation.Methods:This study was a cross-sectional study. Through the evidence-based nursing method, guided by the Ottawa Model, the review indicators and review methods were developed based on the best evidence. The clinical status review of 100 patients who met the inclusion criteria in the Department of Cardiology, Affiliated Hospital of Jiangsu University was conducted from August to November 2022 using a convenience sampling method, and based on the results of the review, an analysis of obstacles and promoting factors was carried out to develop a clinical response.Results:This study included 100 patients with atrial fibrillation, 60 males and 40 females, aged (70.14 ± 10.39) years. Totally 26 best items were included, and 24 review indicators were developed, among which only 4 indicators had a compliance rate of 100% , 2 indicators had a compliance rate of >60% , 5 indicators had a compliance rate of <60% , and 13 indicators had a compliance rate of 0. According to the results of the review, a comprehensive and systematic analysis was conducted from the three dimensions of system, practitioners, patients and family members. For each dimension, obstacles and promoting factors were analyzed in depth from evidence-based change, potential adopters and practical environment.Conclusions:There is a gap between the best evidence and clinical status of long-term oral anticoagulant management in patients with atrial fibrillation. In-depth analysis of obstacle factors, formulate countermeasures, and promote the efficient implementation of evidence in clinical practice.

Objective To study how lipid bilayer fluidity modulates the interaction between β1 integrin and CD40L,as well as the formation of CD40L-mediated tumor cell contact interfaces.Methods Supported lipid bilayers(SLB)with different fluidities were prepared through adjusting the 1,2-dioleoyl-sn-glycero-3-[N-(5-amino-l-carboxypentyl)iminodiacetic acid]succinyl nickel salt(DGS-NTA)content.The functionalization of lipid bilayers was achieved by anchoring fluorescently labeled CD40L molecules onto the membrane surface.The contact interface formation of PC9 cells on the functionalized lipid bilayers was observed through confocal fluorescence imaging and fluorescence recovery after photobleaching(FRAP)experiments,and data of two dimensional(2D)reaction kinetics of β1 integrin and CD40L were extracted from Zhu-Golan plots.Results The diffusion coefficient of molecules in lipid bilayer was negatively correlated with DGS-NTA content.High fluidity of lipid bilayer promoted CD40L accumulation at cell contact interface and expanded the cell contact area.The 2D dissociation constants(2D Kd)of β1 integrin-CD40L complexes were approximately 13,31 and 65 molecules/μm2 for the three lipid bilayers with high,moderate and low fluidities,respectively.Conclusions High fluidity of lipid bilayers significantly facilitates diffusion and aggregation of CD40L to the cell contact interface,thus enhancing β1 integrin-CD40L interaction and the stability of cell contact interfaces.