OBJECTIVE To build a new workflow of pharmacy intravenous admixture services （PIVAS）， effectively connect intelligent equipment， and promote the intelligent development of PIVAS. METHODS Based on intelligent auxiliary equipment， PIVAS workflow was optimized， and a process-oriented model was established. This model integrated intelligent prescription review （automatic prescription review+manual intervention mode）， intelligent labeling， intelligent allocation， intelligent sorting， and finished infusion quality inspection system. Furthermore， an assessment was conducted to examine unreasonable medical order rate of intelligent prescription review， the working efficiency and error rate of intelligent labeling machine and intelligent sorting machine， and the dispensing efficiency and accuracy of intelligent dispensing robot. RESULTS Under the intelligent prescription review mode， the rate of unreasonable medical orders decreased from 0.157% to 0.050% （P＜0.05）； automatic labeling efficiency reached 21.7 sheets/min， surpassing the manual labeling efficiency of 13.8 sheets/min （P＜0.05）， and the daily labeling error rate decreased from 6.1‰ to 2.5‰ （P＜0.05）. Simultaneously operating two dispensing robots significantly improved the efficiency of batch dispensing and reduced the residual amount of liquid medicine （P＜0.05）； additionally， a quality testing system for finished infusion was established， involving appearance， Tyndall effect， insoluble particles， turbidity， absorbance， pH and osmotic pressure， to ensure the quality of finished infusion and reduce the risk of infusion. CONCLUSIONS The new process of PIVAS connected with intelligent devices in our hospital can improve work efficiency， reduce dispensing errors， ensure the quality of finished infusion， and improve the level of pharmaceutical care.

Objective To investigate the causal relationship between obstructive sleep apnea(OSA)and common types of dementia by using Mendelian randomization(MR)analysis methods.Methods Based on summary data from large-scale genome-wide association studies(GWAS),single nucleotide polymorphisms(SNP)highly associated with OSA,Alzheimer's disease(AD),vascular dementia(VaD),dementia with Lewy bodies(DLB),and frontotemporal dementia(FTD)were selected as instrumental variables.The inverse variance weighted method(IVW)was employed as the primary analytical method,and stability tests were conducted by using the simple median method,weighted median method(WME),MR-Egger regression meth-od,simple mode(SM)and weighted mode(WM).Additionally,F-statistics,Cochran'Q test,MR-Egger re-gression intercept test,and leave-one-out method were used for weak instrument variables bias testing,hetero-geneity testing,pleiotropy analysis,and sensitivity analysis,respectively.Causal associations were evaluated by using odds ratios(OR)and 95%CI.Results MR analysis showed that OSA was associated with an increased risk of VaD(OR=1.829,95%CI:1.024-3.266,P<0.05).All F-statistics were>10,indicating no weak in-strumental variables.Cochran'Q test and MR-Egger regression intercept test revealed no heterogeneity and horizontal pleiotropy(P>0.05).Conclusion Genetic-level prediction suggests that OSA is associated with an increased risk of VaD.Early prevention and treatment of OSA may help improve patients'quality of life.

Objective To investigate the effects of 3-methyladenine(3-MA)on mouse mesangial cell line MES-13 cultured in high glucose,and on the kidney of streptozotocin(STZ)-induced mouse model of diabetes and the po-tential mechanism.Methods MES-13 cells were divided into low glucose control group(LG),hyper osmotic pres-sure control group(HOP),high glucose group(HG),3-methyladenine+high glucose group(HG+3-MA)and chloroquine+high glucose group(HG+CQ).The groups were respectively incubated with low glucose DMEM,30 mmol/L mannitol hypertonic control medium,30 mmol/L high glucose medium,5 mmol/L 3-MA+30 mmol/L high glucose medium and 10 mmol/L CQ+30 mmol/L high glucose medium for 24 hours.CCK-8 assay and Western blot were performed.In vivo experiment:Male C57BL/6J mice were induced diabetes for model development by in-tra-peritoneal injection of STZ 60 mg/kg for five consecutive days.After two weeks of injection,the blood glucose was measured.Animals with blood glucose level higher than 16.7 mmol/L(250 mg/dL)were randomly divided in-to diabetes control group(DM),3-MA intervention group(DM+3-MA)and CQ intervention group(DM+CQ),then were fed under the same conditions as normal control group(NC)mice.The DM+3-MA group was given 10 mg/kg of 3-MA aqueous solution by gavage every day,the DM+CQ group was given 50 mg/kg of CQ by intrap-eritoneal injection every three days,the NC group and DM group were given the same amount of normal saline and killed after 6 weeks.The kidneys were stripped for kidney/body weight ratio determination,periodic acid-schiff staining(PAS),MASSON staining microscopy and Western blot.Results In vitro experiment:Compared to the LG group,the cell viability,PCNA expression,ratio of phosphorylated Akt to total Akt(p-Akt/Akt)and ratio of phosphorylated rpS6 to total rpS6(p-rpS6/rpS6)were significantly increased in the HG group(P＜0.05).Com-pared with HG group,the cell viability,PCNA and p-Akt/Akt ratio of HG+3-MA group and HG+CQ group were significantly decreased and p-rpS6/rpS6 ratio of HG+3-MA group was significantly decreased(P＜0.01).In vivo experiment:Compared to NC group,the kidney/body weight ratio,glomerular volume,renal tubular injury index,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 in DM group were all significantly up-regulated(P＜0.05).Compared with DM group,the kidney/body weight ratio,glomerular volume,renal tubular injury in-dex,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 of DM+3-MA group mice were all significantly de-creased(P＜0.05).Conclusions 3-MA can improve glomerular mesangial cell proliferation and renal ECM deposi-tion in early diabetes nephropathy(DN).The improvement of 3-MA in early DN may be related to the inhibition of Akt/rpS6 signaling pathway.

Objective: To investigate the expression changes of cyclin-dependent kinase inhibitor 3(CDKN3) indifferent tumors and its effect on tumor staging, prognosis and immunotherapy. Methods: The expression characteristics of CDKN3 in different cancers using data from TCGA, CCLE, ICGC, and GTEx databases were evaluated. The GEPIA2 platform and Kaplan-Meier analysis were utilized to assess the effect of CDKN3 on tumor pathological staging and survival prognosis. The TIMER platform was employed to explore the influence of CDKN3 on the tumor immune microenvironment and immunotherapy. Its effect on immune checkpoint and key immunotherapeutic predictors using bioinformatics methods was explored. The GeneMANIA tool was used to construct the protein-protein interaction(PPI) network of CDKN3. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Onotology(GO) enrichment analyses were conducted to explore the biological processes and signaling pathways associated with CDKN3. The effect of CDKN3 on HepG2 cell proliferation, invasion, migration, and apoptosis was validated through transfection with CDKN3 siRNA. Results: CDKN3 was found to be widely overexpressed in tumors. High expression of CDKN3 was often associated with advanced pathological staging and poor survival prognosis. CDKN3 expression was negatively correlated with most immune checkpoints and positively correlated with tumor mutation burden(TMB), microsatellite instability(MSI), and mismatch repair(MMR) genes. CDKN3 was associated with cell cycle, cellular senescence, and the p53 signaling pathway. Furthermore, EdU staining, JC-1 staining, Transwell, and Wound Healing assays confirmed that CDKN3 promoted HCC cell proliferation, invasion, and migration while inhibiting apoptosis. Conclusion Abnormal expression of CDKN3 is closely related to tumor staging, prognosis, and immune microenvironment characteristics, making it a potential prognostic marker and immunotherapy adjuvant target in cancer.

Objective:To investigate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN).Methods:A retrospective case series study was conducted. The clinical data of 5 patients with BPDCN treated with VEN combined with azacitidine (AZA) or decitabine (DAC) in the First Affiliated Hospital of Soochow University and Suzhou Hongci Blood Disease Hospital from February 2017 to July 2023 were collected, and the therapeutic effect, adverse reaction and prognosis of all 5 patients were summarized.Results:All 5 BPDCN patients were male with the median onset age [ M ( Q1, Q3)] of 66 years (51 years, 73 years), of which 4 cases were presented with skin lesions and 1 case was presented with lymphadenopathy as the primary symptom. As for the treatment, 3 patients were initially treated with VEN in combination with AZA induction regimen, among which 2 patients achieved complete remission with incomplete blood count recovery (CRi) after 2 cycles of treatment, survived for 26.5 months and 14.6 months, respectively and finally died, and 1 patient achieved partial remission after 1 cycle of treatment and he still survived after 3-month follow-up; 1 patient was initially treated with VEN in combination with DAC induction regimen, and achieved clinical complete remission of non-active disease with residual skin abnormalities after 2 cycles of treatment followed by allogeneic hematologic stem cell transplantation (allo-HSCT) and he was in the state of disease-free survival for 15-month; and another 1 patient experienced a relapse after treatment with acute lymphocytic leukemia-like regimen in combination with allo-HSCT and again achieved CRi after 2 treatment courses of VEN in combination with AZA regimen, and he was in the state of disease-free survival for 30-month follow-up. Treatment-related haematological adverse effects of VEN combined with HMA were mainly neutropenia with fever, reduction of hemoglobin and thrombocytopenia; and non-haematological adverse effects were mainly gastrointestinal reactions such as nausea and vomiting. These adverse events improved with symptomatic supportive therapy, and no treatment-related deaths occurred. Conclusions:BPDCN patients who are unable to tolerate intensive chemotherapy regimens at initial time of diagnosis may attempt induction therapy with VEN+HMA regimen, which has a manageable adverse reaction and may serve as a bridge to allo-HSCT.

Objective To investigate the medication and compatibility patterns of traditional Chinese medicine(TCM)compound patents in the treatment of epilepsy through data mining research.Methods Data on TCM compound patents for treating epilepsy were retrieved from the China National Intellectual Property Administration's patent publication website.Descriptive analysis,association rule analysis,and cluster analysis were conducted using softwares such as Excel,Origin 2021,R 4.3.1 and Cytoscape 3.9.1,and the relevant topological property values were calculated to construct the core complex network.Results A total of 346 TCM compound patents for treating epilepsy were included,involving 738 different herbs.The top 5 frequently used herbs were Acorus tatarinowii,Gastrodia elata,Buthus martensii,Eupolyphaga seu steleophaga,and Uncaria rhynchophylla.The predominant drug category was liver-soothing and wind-extinguishing drugs.Cluster analysis identified two major categories of drug combinations,and the core combination in the co-occurrence network was Rhizoma acori tatarinowii-Scorpio-Gastrodiae rhizoma-Bombyx batryticatus-Uncariae ramulus cum uncis.A total of 23 association rules were obtained.Conclusion This study reveals the primary characteristics of treating epilepsy,which mainly focus on therapeutic directions such as soothing the liver and suppressing wind,calming wind to arrest convulsions,and calming the mind to tranquilize the spirit.It incorporates individualized dialectical diagnostic and treatment strategies,such as promoting blood circulation and resolving stasis,invigorating the spleen,and transforming phlegm.This discovery aims to provide reference and reference value for the clinical treatment of epilepsy in traditional Chinese medicine.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

At present, implant surgery robots have basically achieved "surgical intelligence", but "brain-inspired intelligence" of robots is still in the stage of theory and exploration. The formulation of a clinical implantation plan depends on the timing of implantation, implantation area, bone condition, surgical procedure, patient factors, etc., which need to evaluate the corresponding clinical decision indicators and clinical pathways. Inspired by evidence-based medicine and the potential of big data and deep learning, combined with the data characteristics of clinical decision indicators and clinical pathways that can be quantitatively or qualitatively analyzed, this review simulates the cognitive behavior and neural mechanisms of the human brain and proposes a feasible brain-inspired intelligence scheme by predicting the decision indices and executing clinical pathways intelligently, that is, "select clinical indicators and clarify clinical pathways -- construct database -- use deep learning to intelligently predict decision indicators -- intelligent execution of clinical pathways -- brain-inspired intelligence of implant decision-making". Combined with the previous research results of our team, this review also describes the process of realization of brain-inspired intelligence for immediate implant timing decisions, providing an example of the comprehensive realization of brain-inspired intelligence of implant surgery robots in the future. In the future, how to excavate and summarize other clinical decision factors and select the best way to realize the automatic prediction of evidence-based clinical indicators and pathways and finally realize the complete intellectualization of clinical diagnosis and treatment processes will be one of the directions that dental clinicians need to strive for.

OBJECTIVE: To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. METHODS: Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. RESULTS: Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. CONCLUSIONS Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
Male ; Animals ; Swine ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ferroptosis ; Brain Injuries ; Glutathione ; Cardiopulmonary Resuscitation ; Ligases ; Iron

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L^-1 QLBTWT for 24 h， the half-inhibitory concentration （IC₅₀） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L^-1， respectively， based on which， 9.5， 19， 38 mg·L^-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L^-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L^-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G₁） phase in 9.5， 19 and 38 mg·L^-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L^-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L^-1 QLBTWT group and 19 mg·L^-1 QLBTWT+10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.