Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome elements with language function and activities of daily living(ADL)in patients suffering post-stroke aphasia(PSA).Methods Ninety-eight PSA patients hospitalized at the College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine from April 2023 to April 2024 were selected.The language function,TCM syndrome elements,and their correlations were analyzed.Results(1)Among PSA patients,males outnumbered females.PSA patients exhibited different performances on various aphasia-related scales,with language impairments mainly concentrated in naming and spontaneous speech.(2)The distribution of TCM syndrome elements varied in PSA patients with different age groups.In the age group＜50 years old,qi obstruction(100.00%),phlegm syndrome(100.00%),and dampness syndrome(100.00%)were predominant.In the age group of 50-59 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.30%)were predominant.In the age group of 60-69 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.15%)were also predominant.In the age group of 70-79 years old,qi deficiency syndrome(100.00%)was predominant.In the age group of 80-89 years old,syndromes such as qi insecurity,qi obstruction,qi deficiency,phlegm,yang hyperactivity,blood stasis,wind stirring,and blood cold were concentrated(all 100.00%).However,there were no statistically significant differences in the distribution of TCM syndrome elements among various age groups(P＞0.05).(3)The distribution of deficiency and excess syndrome elements varied in PSA patients with different genders.Among deficiency syndrome elements,yang hyperactivity,qi deficiency,and yin deficiency were predominant in males,while yang hyperactivity,qi deficiency,and blood deficiency were predominant in females.Among excess syndrome elements,phlegm syndrome,qi obstruction,and dampness syndrome were predominant in males,while phlegm syndrome,qi obstruction,and qi stagnation syndrome were predominant in females.However,there were no statistically significant differences in the distribution of deficiency and excess syndrome elements between genders(P＞0.05).(4)After controlling the factors of age group and gender,partial correlation analysis of syndrome elements and language function showed that among the disease-location syndrome elements,spontaneous naming(r=-0.588,P=0.027)and sematic cued naming(r=-0.558,P=0.038)in the Boston Naming Test(BNT)were negatively correlated with the large intestine;among the disease-nature syndrome elements,BNT sematic cued naming(r=0.821,P＜0.001)was positively correlated with qi sinking,while BNT spontaneous naming was negatively correlated with blood heat(r=-0.544,P=0.044)and was positively correlated with fluid depletion(r=0.860,P=0.028);BNT recognitive naming was positively correlated with external wind(r=0.966,P=0.034);errors in BNT sematic cued naming were negatively correlated with qi sinking(r=-0.540,P=0.005);the Modified Barthel Index(MBI)was positively correlated with essence deficiency(r=0.572,P=0.021).Conclusion The TCM syndrome elements of phlegm,qi block,yang hyperactivity,and qi deficiency are commonly seen in PSA patients.There is a certain correlation of language function and ADL with TCM syndrome elements in PSA patients.

Objective To analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.

Objective:To summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early treatment.

Objective:To summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early treatment.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

AIM:To investigate whether Miaoyao Tongfeng prescription(MTP)attenuates oxidative stress in-jury in gouty arthritis rats by regulating Kelch-like epicklorohydrin-related protein 1(Keap1)/nuclear factor E2-related fac-tor 2(Nrf2)signaling pathway.METHODS:Fifty male Sprague-Dawley rats were randomly divided into control group,model group,MTP group,Nrf2 inhibitor all-trans retinoic acid(ATRA)group and MTP+ATRA group.The 3%potassium oxonate solution(10 mL/kg)was injected intraperitoneally twice a day for 1 week,and then 0.2 mL sodium urate suspen-sion(25 g/L)was injected into the right knee joints to establish the gouty arthritis model.All rats were sacrificed 48 h af-ter modeling.Grades of swelling in the knee joints were evaluated,and HE staining was used to observe the pathological changes of knee joints.Serum levels of superoxide dismutase(SOD),malondialdehyde(MDA)and interleukin-1β(IL-1β)were detected using kits.The mRNA levels of Nrf2,Keap1,heme oxygenase-1(HO-1),IL-1β,NAD(P)H:quinone oxidoreductase 1(NQO1)in the synovial membrane of the knee joints were detected by qRT-PCR.Western blot was used to detect the expression of Nrf2,Keap1 and NQO1 in the synovial membrane of the knee joints.RESULTS:Compared with model group,MTP significantly reduced the degree of knee joint swelling,and attenuated the pathological injury of knee synovial membrane.It also inhibited the expression of MDA and IL-1β,but increased the expression of SOD.The mRNA expression of HO-1,and the mRNA and protein expression of Nrf2 and NQO1 in synovium were up-regulated,while the levels of IL-1β mRNA,Keap1 mRNA and Keap1 protein were down-regulated.CONCLUSION:Miaoyao Tongfeng prescription shows promise in the prevention and treatment of gouty arthritis through regulating Nrf2 and down-stream anti-oxidation genes.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.