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.

OBJECTIVE: To investigate the transfusion and infusion warmer manufacturers, combine the use failures to analyze adverse events, and provide support for enterprise risk management and clinical safe use. METHODS: The sentinels from 7 manufacturing enterprises and 11 medical institutions that participated in Shandong Province's key monitoring program during the "14th Five-Year Plan" period were targeted. This was done by understanding the equipment's principles, structures, and quality control. Additionally, real-world data from January 2019 to December 2023 were collected to count adverse events. RESULTS: During production, there are risks in switching power supply stability and solder joint firmness. Fifteen kinds of faults occurred during use, and common faults such as inability to heat, unable to turn on the machine, and bubbles in the infusion tube accounted for more than 80%. CONCLUSION There are many risk points and failures for transfusion and infusion warmers, so enterprises should improve processes and quality control to address risks, and medical institutions should formulate specifications and maintenance plans to provide targeted theoretical basis for supervision.
Blood Transfusion/instrumentation* ; Risk Factors ; Quality Control ; Humans ; Risk Management ; Equipment Failure

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Kirsten rat sarcoma viral oncogene homolog(KRAS)is a type of gene closely related to human tumors.And it's an important medical index to access the tumor development,prognosis and the efficacy of chemoradiotherapy.RAS mutations,in which KRAS mutations account for up to 85%,are the most common oncogenic driving mutations in human tumors.The most frequent KRAS mutation sites are codons 12,13,61 and 146.Codon G12,as the most frequently mutated one,can be divided into multiple subtypes,with G12D mutation being the most common,followed by G12V,G12C,etc.Colorectal cancer(CRC)is one of the tumors with the highest frequency of KRAS mutations.Both G12D and G12V are the most common mutation subtypes in CRC.In the field of treatments for CRC with KRAS mutations,targeted therapy had not been possible until the release of KRASG12C inhibitors in 2013,and new drugs have been developed one after another since then.This study summarized the mutations of KRAS and the advances in clinical research,including the latest advances in targeted drugs,chemotherapy drugs,immunotherapy drugs,ferroptosis,and other treatment methods.Among them,in terms of targeted drugs,this review explored KRASG12C inhibitors(sotorasib,adagrasib,D-1553,IBI351,etc.),anti-angiogenic drugs(monoclonal antibodies such as bevacizumab,remdesizumab,etc),small molecule multi-target tyrosine kinase inhibitors such as sunitinib,etc.In terms of immunotherapy drugs,there have also been many advances,such as the ARETHUSA clinical trial,which found that temozolomide reduced the tumor mutational burden(TMB)of O-6-methylguanine-DNA methyltransferase(MGMT)deficiency and RAS mutation in patients with advanced metastatic colorectal cancer(mCRC),providing innovative ideas for patient immunotherapy.For example,the combination of xindilimab with bevacizumab,oxaliplatin,and capecitabine can be used for first-line treatment of RAS mutations,microsatellite stability(MSS),and unresectable mCRC.Relevant studies have shown that the combination therapy has good therapeutic potential and controllable tolerability safety.This review explored the mechanisms of KRAS mutations and the latest advances in clinical research and treatment,in order to provide reference for the treatment of KRAS mutated colorectal cancer.

Objective To investigate the safety and efficacy of sodium fluorescein-guided microsurgery in children with medulloblastoma,and to analyze the surgical efficacy and prognosis.Among them,12 cases underwent unilateral telovelar approach,2 cases underwent bilateral telovelar approach,and 6 cases underwent telovelar approach combined with transvermian approach.The intraoperative dose of sodium fluorescein was 2 mg/kg.Methods The clinical data of 20 patients with medulloblastoma treated with fluorescein sodium assisted microsurgery from January 2018 to August 2023 in Xinjiang Autonomous Region People's Hospital were retrospectively analyzed.Results Of the 20 patients,12 were male and 8 were female.The mean age of onset was(7.9±3.7)years.In all cases,there was clear tumor fluorescence,none of the cases had adverse reaction associated with the use of sodium fluorescein.There were 16 cases of gross-total resection,3 cases of near-total resection,1 case of partial resection,1 case of intracranial infection,2 case of subcutaneous effusion,2 cases of cerebellar mutism.The follow-up time was from 3 to 72 months.5 cases did not receive sufficient radiotherapy and chemotherapy,and 9 cases died due to tumor progression or recurrence.In all cases,the longest overall survival was 72 months,the mean survival time was 39.2 months,and the median survival time was 41.2 months.Conclusion Fluorescein sodium assisted microsurgery is safe and effective in pediatric medulloblastoma surgery.

Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P＜0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P＜0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.

Objective:To investigate the potential effect and mechanism of docosahexaenoic acid(DHA) on hippocampal neuronal apoptosis and c-Jun N-terminal kinase(JNK) protein in rats with subarachnoid hemorrhage(SAH).Methods:Forty eight SPF-grade male SD rats were randomly divided into control group, sham group, model group and DHA intervention group according to the random number table method, with 12 rats in each group.The rats in model group and DHA group were injected with autologous blood(0.3 mL) into the optic chiasma to establish the SAH model.Rats in model group were intraperitoneally injected with DHA(35 mg/kg) 3 hours after SAH model establishment, rats in sham operation group were injected with 0.3 mL 0.9% sodium chloride solution into the optic chiasma, and rats in control group were fed normally.Neurobehavioral function of all rats was evaluated after 24 hours.The apoptosis of neuron was observed by TUNEL staining, and the expression of phosphorylated JNK(p-JNK)and apoptosis-related proteins Bax and Bcl-2 was observed by Western blot.Statistical analysis was performed using GraphPad Prism 7.0 software.One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1)The differences in neurobehavioral function scores among the 4 groups of rats were statistically significant( F=103.60, P<0.05), the neurobehavioral function scores in model group(8.67±1.37) and DHA intervention group(13.67±1.51) were lower than that in control group(18.00±0.00) and sham group(17.67±0.52)( all P<0.05), while the neurobehavioral function score in DHA intervention group was higher than that in the model group( P<0.05).(2)The results of TUNEL staining showed that there were statistical differences in the number of hippocampal neuron apoptosis among the 4 groups( F=30.76, P<0.05), the number of hippocampal neuron apoptosis in model group(55.67±5.28) was higher than those in control group(25.83±7.06) and sham group(25.50±6.72) (both P<0.05), the number of hippocampal neuron apoptosis in DHA intervention group(35.17±5.78) was lower than that in model group.(3)The results of Western blot showed that there were no statistical differences in the Bax protein levels among the four groups( F=2.00, P>0.05).There were statistical differences in the expression levels of Bcl-2, p-JNK and Bax/Bcl-2 ratio among the 4 groups( F=8.48, 5.69, 5.39, all P<0.05).There was no statistical difference in Bcl-2, p-JNK protein levels and Bax/Bcl-2 ratio between the control group and sham group(all P>0.05).The p-JNK protein levels and Bax/Bcl-2 ratio in model group ((1.93±0.25), (2.05±0.86)) were higher than those in sham group ((1.42±0.33), (1.05±0.26)) (both P<0.05), the Bcl-2 protein level in model group (1.04±0.23) was lower than that in sham group (1.61±0.16) ( P<0.05).The p-JNK protein level and Bax/Bcl-2 ratio in DHA intervention group((1.43±0.33), (1.19±0.30)) were lower than those in model group(both P<0.05), the Bcl-2 protein level in DHA intervention group(1.42±0.28) was higher than that in model group( P<0.05). Conclusion:DHA can reduce neuronal apoptosis, inhibit the activation of p-JNK and improve neurological function of SAH model rats.

Objective To standardize nursing management on postoperative patients with a left ventricular assist-ant device(LVAD).Methods The first draft of the Consensus was formed on the basis of literature review.2 rounds of expert consultations and a round of online meeting discussion were held for adjustments and modifications the draft of the Consensus.Results The recovery rate of the inquiry questionnaire was 93.75%.The authority coefficients of the 2 rounds of inquiry experts were 0.927 and 0.920.The concentration degree of expert opinions for each indicator was greater than 3.5 score,and the coefficient of variation was less than 0.25.The Kendall harmony coefficients for 2 rounds of correspondence were 0.402 and 0.407(P<0.01).The final Consensus formed through expert consultations and meetings includes 7 themes:hemodynamic monitoring,LVAD function monitoring,coagulation function monitoring,percutaneous cable and wound care,exercise rehabilitation care,health education and guidance,and pre-discharge assessment.Conclusion The Consensus is scientific,rigorous,and authoritative.The Consensus covers all aspects of postoperative care for patients with LVAD,and it will benefit to clinical practice.

Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P＜0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P＜0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P＜0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P＜0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P＜0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)％vs(62.77±5.43)％,P＜0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.

Objective:To screen the host interaction proteins of the severe fever with thrombocytopenia syndrome virus(SFTSV)nonstructural protein(NSs)by immunoprecipitation combined with mass spectrometry analysis,to discuss the functions,subcellular localization,and biological pathways of these interaction proteins,and to provide the basis for clarifying the replication and pathogenic mechanism of SFTSV.Methods:The eukaryotic expression vectors pSFTSV-NSs-Flag(experimental group)and Flag-CMV-3(negative group)were transfected into the human embryonic kidney 293T cells,and contorl group(no treatment)was set up.The lysates of the cells in various groups were collected,and the expression and localization of SFTSV NSs in the host cells were verified by indirect immunofluorescence and Western blotting methods.The protein lysates were treated with protein A/G and immunoprecipitation was used to enrich host proteins binding to NSs.The captured interaction proteins were initially analyzed by silver staining and Coomassie brilliant blue staining to observe the differential protein bands in various groups;liquid chromatography-tandem mass spectrometry was used to obtain the information of protein sequences;the reliable proteins were retained and searched by UniProt database;Gene Ontology(GO)functional enrichment analysis,IPR,eukaryotic orthologous groups(KOGs)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,subcellular localization,and transcription factor(TF)functional annotation were used to determine the subcellular structure,gene functions,and biological processes of the interaction proteins.Results:The immunofluorescence results showed that the SFTSV NSs expressed a single specific band at relative molecular mass 33 000 and was localized in the cytoplasm in a granular inclusion body-like manner.The silver staining and Coomassie brilliant blue staining results showed there were significant differential protein bands between experimental group and negative group.The mass spectrometry results identified 46 potential interaction proteins.The GO functional enrichment analysis,KOGs functional annotation,and KEGG signaling pathway enrichment analysis results showed that the biological pathways related to viral translation,cellular metabolism,and protein transport were enriched with a considerable number of proteins.Eight annotated proteins had intermediate filament domains.The highest percentage of subcellular localization was cytoplasmic proteins,consistent with the NSs localization site.The TF functional annotation analysis results showed one protein from the NF-Y family.Conclusion:The interaction proteins play roles in assisting the proper protein folding,participating in the cribosome translation,and forming the cytoskeleton,which may be involved in antiviral replication.These proteins can be used as candidate proteins for further study on the replication mechanism of SFTSV.