Multiple sclerosis(MS)is a complex autoimmune disorder characterized by inflammatory demyelination in the central nervous system.Prominent symptoms include damage to myelin sheaths in the brain,optic nerve,and spinal cord,as well as axonal dysfunction;however,the exact causes and mechanisms of MS remain unclear.Genetic and environmental factors are thought to interact via autoimmune mechanisms,potentially triggering the disease.Recent studies suggest that abnormal activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play a critical role in the pathogenesis of MS.In this context,this review summarizes the molecular mechanisms underlying NLRP3 activation and its connection to MS,considering relevant literature from the past decade.The findings aim to provide insights into the progression of MS and to identify potential therapeutic strategies by elucidating the underlying mechanisms.

CRM 197(cross-reacting material 197),a naturally occurring mutant of diphtheria toxin,is a safe and effective vaccine vector and extensively used on developing conjugate or combined vaccines.The mutant loses its enzymatic activity,but fully retains its receptor-binding ability and immunogenicity.In current work,the diphtheria toxin mutant CRM 197 and its fusion proteins with the receptor-binding do-main of botulinum neurotoxin serotype E(EHc)were developed using genetic engineering technology.These recombinant proteins were confirmed by Western blotting and SDS-PAGE.BALB/c mice were im-munized with the CRM197-EHc and EHc-CRM197 fusion proteins,and their immunogenicity was evalua-ted.These two fusion protein molecules,CRM197-EHc and EHc-CRM197,as subunit vaccines,elicited a robust humoral immune response targeting both CRM197 and EHc antigens in the immunized mice.Compared to the mixture of CRM197 and EHc,the mice vaccinated with the fusion proteins(CRM197-EHc and EHc-CRM197)induced higher levels of anti-CRM197 antibodies,and the mice vaccinated with EHc-CRM197 also generated strongest anti-EHc antibodies.Consequently,as a carrier molecule in the fusion protein vaccine,EHc enhances the immunogenicity of CRM197 molecules.Likewise,CRM197 boosts the immunogenicity of EHc in the EHc-CRM197 fusion protein.

Objective Piperazine derivatives are a group of emerging psychoactive substances with excitatory and hallucinogenic effects on the central nervous system.This study established a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)screening method for the detection of 40 piperazine compounds in urine.Methods A 200 μL urine sample(spiked with an internal standard at 1 ng/mL)was subjected to liquid-liquid extraction with ethyl acetate.After nitrogen evaporation,the residue was redissolved in 200 μL methanol and injected for analysis.Separation was performed on a Waters Acquity UPLC? HSS T3 column(100 mm × 2.1 mm,1.8 μm).The mobile phase consisted of(A)20 mmol/L ammonium acetate buffer containing 0.1％formic acid and 5％acetonitrile,and(B)acetonitrile.Gradient elution was applied,and detection was carried out in multiple reaction monitoring(MRM)mode.Quantification was achieved using an internal standard calibration curve.Results The 40 piperazine substances demonstrated good linearity within the range of 1-50 ng/mL,with correlation coefficients of 0.995-0.998.The extraction recovery ranged from 51.51％to 104.1％.Intra-day precision was below 5％,while inter-day precision ranged from 1.61％to 10.17％.Accuracy was between-7.84％and 8.77％.The limits of detection were 0.2-1 ng/mL,and the limit of quantification was 1 ng/mL.Conclusion The proposed method requires only a small sample volume,exhibits high sensitivity,selectivity,and stability,and offers short run times.It is suitable for the qualitative and quantitative determination of piperazine derivatives in urine in forensic toxicology practice.

Indocyanine green(ICG)is one of the near-infrared fluorescent contrast agents approved for clinical use in fluorescence-guided surgery.Although widely applied,it still has some limitations.In recent years,various targeted fluorescent agents have been explored in pancreatic cancer patients;however,there is still no standardized consensus among surgeons regarding fluorescence-guided surgery for pancreatic cancer.In 2023,the first the international consensus report on fluorescent surgery navigation for pancreatic tumors was published,gathering perspectives from 38 pancreatic surgeons worldwide on current practices and future directions.A total of 76 statements were anonymously voted on using the Delphi method,resulting in 61 recommended statements.This consensus offers valuable guidance for the implementation of fluorescence-guided surgery in pancreatic tumor operations in China,yet its clinical application should be adapted in consideration of local expert opinions and patient-specific factors.This article interprets key aspects of the consensus,including the use of ICG,intraoperative fluorescence imaging techniques,and the fluorescence heterogeneity of pancreatic tumors,in combination with the authors'clinical experience,with the aim of providing reference and insight for the application of fluorescence-guided surgery in pancreatic tumors.

Objective:To observe the longitudinal changes of symptoms in the irradiation area of patients with postoperative radiotherapy for breast cancer,and investigate the correlative symptom indexes for predicting acute radiation dermatitis during radiotherapy.Methods:This study was designed as a prospective longitudinal study.A total of 103 patients with breast cancer who received three-dimensional con-formal radiotherapy in The Fourth Hospital of Hebei Medical University from May 2022 to December 2022 were enrolled using convenience and purposive sampling methods.The patients received a total of 50 Gy/25 radiotherapy sessions.We conducted weekly observations of five symptoms-itching,pain,swelling,burning,and tightness-in the irradiated area,for a total of six weeks.The incidence of symptoms associ-ated with radiation dermatitis across different severity levels was compared.We calculated the optimal number of symptoms for the occur-rence of grade 2 or higher radiation dermatitis,evaluated the predictive effect using the subject's work characteristic curve(ROC),and com-pared the risk of radiation dermatitis with the number of symptoms by applying a binary Logistic regression.Results:A total of 103 patients were included in the study.The total severity scores of symptoms were 0(0,0),0(0,0),0(0,1),1(0,2),2(1,3),3(2,4),respectively,show-ing a gradually increasing trend.From the 20 Gy/10-fraction radiotherapy point onward to the completion of radiotherapy,symptom scores exhibited statistically significant deviations from baseline values(P<0.001).From the beginning of 30 Gy/15 sessions to the end of radiother-apy,symptom scores were higher in patients with grade 2 and above dermatitis compared to those with dermatitis of less than grade 2(Z=2.12,2.81,4.08,P=0.034,0.005,0.001);at the end of 50Gy/25 sessions,the incidence rates of pruritus,pain,swelling,tightness,and burning were 68.9%(71 cases),68.9%(71 cases),46.6%(48 cases),36.9%(38 cases),and 15.5%(16 cases),respectively.At the 30 Gy/15 and 40 Gy/20 radiotherapy sessions,the optimal number of predicted symptoms were two and three,respectively.The corresponding areas under the ROC curve were 0.632 and 0.666.Sensitivity values were 48.6%and 43.2%,while specificity values reached 77.3%and 81.8%,re-spectively(95%CI:0.517-0.746,0.558-0.775,P=0.027,0.005).The subjects were assigned into low-risk and high-risk groups using the op-timal cut-off values,and binary Logistic regression showed that the risks of grade 2 and higher radiation dermatitis in the high-risk group were 3.39 and 3.58 times higher than that in the low-risk group(OR=3.388,95%CI:1.400-8.197,P=0.007;OR=3.584,95%CI:1.430-8.985,P=0.006).Conclusions:The symptoms of radiation dermatitis have appeared early and worsened with the severity of dermatitis.We should closely observe these symptoms throughout treatment.The risk of grade 2 and above radiation dermatitis increased when the number of symptoms was≥2 at 30 Gy/15 times and≥3 at 40 Gy/20 times.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Objective To investigate the anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective To analyze changes of preoperative T lymphocyte immunity and humoral immunity,and their relationship with pathological characteristics in patients with primary hepatocellular carcinoma(HCC).Methods A total of 150 patients with primary HCC underwent elective surgical treatment were enrolled as the HCC group,while 150 healthy controls during the same period were enrolled as the control group.Before surgery,the levels of peripheral blood CD3+,CD4+and CD8+were detected by flow cytometry,and CD4+/CD8+was calculated.The levels of IgA,IgG and IgM in peripheral blood were detected by immunoturbidimetry.The pathological characteristics of HCC patients were collected,and the differences of preoperative immune indexes in patients with different pathological characteristics were compared.The receiver operating curve(ROC)was used to evaluate the predictive value of immune indicators for pathological characteristics.Results The levels of CD3+,CD4+and CD4+/CD8+were lower in the HCC group than those in the control group,while levels of CD8+,IgA,IgG and IgM were higher in the HCC group than those in the control group(P＜0.05).The levels of CD3+,CD4+and CD4+/CD8+were lower in patients with lymph node metastasis than those of patients with distant lymph non-metastasis(P＜0.05).The levels of CD8+,IgA,IgG and IgM were higher in patients with lymph node metastasis than those of patients without metastasis(P＜0.05).The results of receiver operating characteristic(ROC)curves showed that area under the curve(AUC)values of CD3+,CD4+,CD8+,CD4+/CD8+,IgA,IgG,and IgM for predicting lymph node metastasis in HCC patients were 0.810,0.741,0.770,0.707,0.756,0.738 and 0.727.Conclusion There are abnormal changes of preoperative T lymphocyte immunity and humoral immunity in patients with primary HCC,which are closely related to lymph node metastasis.

Objective To explore the clinical infection distribution and antifungal resistance characteristics of the Stephanoascusciferrii(S.ciferrii)complex.Methods Clinical fungal culture and isolation data from Nanjing Drum Tower Hospital from 2012 to 2023 were retrospectively analyzed.The annual isolation quantity,proportion,and distribution of infection sites of S.ciferrii were statistically analyzed.The minimum inhibitory concentrations(MICs)of isolated strains against common antifungal agents were detected by ATB Fungus 3 fungal susceptibility test kit,and their resistance was analyzed.Results From 2012 to 2023,a total of 26 602 fungal strains were isola-ted in this hospital,including 79 strains of the S.ciferrii complex.Compared with 2012-2017,the isolation rate of S.ciferrii complex increased from 2018 to 2023(0.06％vs 0.43％,P＜0.001).There were 69 cases of super-ficial infection,including infection of ear canal(n=67)and skin(n=2).92.75％(n=64)of the patients were im-munocompetent individuals.There were 10 cases of invasive infection,including infection of urinary tract(n=5),respiratory tract(n=2),biliary tract(n=1),pacemaker pouch(n=1),and vagina(n=1).70.00％of the pa-tients had other underlying diseases,including 3 cases of immunosuppressed patients who died due to combined in-fection with the S.ciferrii complex.The MICs detection results showed that the MIC50 and MIC90 of fluconazole were 32 μg/mL and 128 μg/mL,respectively;the MIC50 and MIC90 of amphotericin B were 0.5 μg/mL and 2 μg/mL,respectively.Conclusion S.ciferrii complex mainly causes ear canal infection and has the dual pathogenic ability to cause superficial and invasive infection.The isolated strains showed higher MIC values for fluconazole and lower MIC values for amphotericin B.The mortality is high in immunosuppressed patients combined with invasive infec-tion caused by S.ciferrii.

Objective:To understand the activity concentrations of varying chemical forms of 131I in nuclear medicine workplaces and assess the internal irradiation doses of 131I to workers. Methods:A high-volume air sampler was used for air sampling of 131I. Glass fiber filters, activated carbon filters, and iodine cartridges, which were connected in series, were employed to collect aerosol iodine, gaseous inorganic iodine, and gaseous organic iodine, respectively. A method for analyzing the activity of 131I unevenly distributed in the iodine cartridge was developed, and an HPGe γ spectrometer was used to determine the activity of 131I in samples collected from the nuclear medicine workplaces of 15 hospitals. Results:The concentrations of aerosol iodine, inorganic iodine, and organic iodine in 15 hospitals were determined at 0.19-206.67, 0.27-138.45, and 2.35-3 821.11 Bq/m 3, respectively, with arithmetic means of 22.04, 12.79 and 365.08 Bq/m 3, respectively. The maximum annual committed effective doses of varied forms of 131I inhaled by workers were determined at 0.19, 0.19, and 3.81 mSv, respectively, with a maximum total committed effective dose of 4.13 mSv. Conclusions:Gaseous organic iodine is identified as the primary form of 131I in the air within nuclear medicine workplaces. Therefore, it is necessary to highlight the monitoring and protection of gaseous organic iodine.