Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

Objective:To investigate the diagnostic value of serum homocysteine(Hcy),soluble stromelysin 2(sST2)and cystatin C(CysC)for chronic heart failure(CHF).Methods:A total of 86 CHF patients admitted in our hospital were se-lected as CHF group,and 86 healthy individuals who underwent physical examination simultaneously were selected as healthy control group.Serum levels of Hcy,sST2 and CysC,plasma level of N terminal pro brain natriuretic peptide(NT-proBNP)and cardiac function indexes[left atrial diameter(LAD),left ventricular end diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF)]were measured between two groups.Pearson correlation analysis was used to analyze the correlation among serum Hcy,sST2,CysC,plasma NT-proBNP and cardiac function indexes.Receiver operating characteristic curve(ROC)was drawn to evaluate the diagnostic value of serum Hcy,sST2 and CysC and their combined detection for CHF.Results:Compared with healthy control group,there were significant rise in scrum levels of Hcy,sST2 and CysC,plasma NT-proBNP level,LAD and LVEDd,and significant reduction in LVEF in CHF group,P=0.001 all.Pearson correlation analysis indicated that serum Hcy,sST2 and CysC levels were significant positively correlated with plas-ma NT-proBNP level,LAD and LVEDd(r=0.385～0.511,P＜0.05 or＜0.01),and significant inversely correlated with LVEF(r=-0.424～-0.402,P＜0.05 all).AUC of single detection of serum Hcy,sST2 and CysC diagnosing CHF was 0.624,0.720 and 0.870 respectively,and AUC of their combination was 0.865,which was significantly higher than any single detection,P＜0.05 or＜0.01.Conclusion:Serum levels of Hcy,sST2 and CysC abnormally increase in CHF patients,which can be used as auxiliary diagnostic indexes for CHF.The triple combined detection is of great signifi-cance for the diagnosis of CHF.

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

Objective:To investigate the mid-and long-term clinical efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type developmental dysplasia of hip (DDH) in adolescents.Methods:A total of 28 adolescent DDH patients with unilateral dislocation who underwent modified Colonna capsular arthroplasty from January 2016 to January 2018 in the 920th Hospital of Joint Logistics Support Force of People's Liberation Army were retrospectively analyzed. There were 4 males and 24 females, aged 16.5±5.0 years (range, 10-25 years). The mean body mass index was 21.2±1.1 kg/m 2 (range, 18.7-24.1 kg/m 2). According to DDH classification, 10 cases were Tonnis type III and 18 cases were Tonnis type IV. The postoperative lateral center-edge angle, acetabular coverage, femoral anteversion angle and leg length discrepancy were measured. The operation time, intraoperative blood loss, visual analogue scale (VAS) of hip pain, Harris hip score (HHS) and congenital dislocation of the hip score were recorded. Results:All patients successfully completed the operation and were followed up for 72.1±5.2 months (range, 60-84 months). The operation time was 81.6±4.3 min (range, 70-90 min), the intraoperative blood loss was 177.5±12.6 ml (range, 160-200 ml), and the hospital stay was 6.8±0.7 days (range, 6-9 days). The VAS score of the hip joint was 1.8±0.6 before operation and 2.3±0.6 at the last follow-up, and the difference was not statistically significant ( t=2.845, P=0.224). The preoperative HHS score was 57.1±5.9, and it increased to 87.3±4.0 at the last follow-up, and the difference was statistically significant ( t=-22.141, P=0.001). At the last follow-up, the femoral anteversion angle was 17.0°±1.5°, which was lower than that before operation 41.6°±2.4°, with a statistically significant difference ( t=-44.868, P=0.008). The leg length discrepancy was 10.2±2.3 mm, which was lower than that before operation (26.4±6.1 mm), with a statistically significant difference ( t=-12.892, P<0.001). The lateral center-edge angle was 28° (26°, 30°), and the acetabular coverage rate was 78% (76%, 79%). The curative effect evaluation standard score of congenital dislocation of the hip was 24 (16.7, 25.7) points, including 7 excellent cases, 14 good cases, 4 fair cases, and 3 poor cases. The excellent and good rate was 75% (21/28). Conclusion:The modified Colonna arthroplasty for the treatment of unilateral dislocation DDH in adolescents has good mid-and long-term hip function recovery and radiographic improvement.

Objective To investigate the effect of fibroblast growth factor receptor 3(FGFR3)on articular cartilage superficial zone cells(SPZCs).Methods C57 mice were randomly divided into two groups:a sham operated group(sham group)and a group of surgically induced unstable medial meniscus model group(DMM group).The histological morphology of articular cartilage was microscopied by Safranin O/Fast Green-stained in 4 weeks and 8 weeks after surgery.Apoptosis and FGFR3 protein expression were detected by immunohistochemical staining mi-croscopy.Primary SPZCs were separated and randomly divided into control group and Fgfr3 knockdown treatment group.The genes and protein expression related to chondrocyte extra cellular matrix synthesis,degradation and chondrocytehypertrophy were detected by RT-qPCR and Western blot.Results Compared with the sham group,the keen cartilage of mice in DMM group showed a pioneer damage of SPZCs after surgery;Immunohistochemistry results showed an increase in chondrocyte apoptosis and a decrease in expression of MMP-13 and FGFR3(P＜0.05).Primary SPZCs were transfected with small interfering RNA(siRNA)to knockdown Fgfr3;RT-qPCR results showed that the mRNA expression of genes related to the synthesis of cartilage extracellular matrix aggrecan and Col2 was reduced;And the mRNA expression of extracellular matrix degradation-related genes Mmp13 and Adamts5 was increased.The mRNA expression of chondrocyte hypertrophy-related genes Col10 and Mmp13 was increased.Western blot and RT-qPCR results were consistent and the expression l of MMP13 protein was significantly increased,while the expression of collagenⅡand aggrecan protein was significantly decreased(P＜0.05).Conclusions Knockdown of Fgfr3 induces damage to primary SPZCs in mice resulting in early osteoarthritis(OA)development.

Objective To investigate the binding and carrying effects of human serum albumin(HSA)from various sources on sphingosine-1-phosphate(S1P).Methods Utilizing human plasma-derived HSA(pHSA)and recombinant HSA(rHSA)samples as the focal points of our investigation,LC-MS/MS technology was employed to meticulously compare and an-alyze the disparities in S1P content among the aforementioned samples.Subsequently,under physiological concentration condi-tions,S1P was directly introduced to HSA samples for loading processing,facilitating a comprehensive comparison of the bind-ing efficacy of HSA from different sources to S1P.Within a serum-free culture setting,HSA samples from various sources were co-cultured with HUVEC cells.The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed,allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was cal-culated using surface plasmon resonance(SPR)technology.Furthermore,leveraging AutoDock Vina software and the Mol-prophet platform,the molecular docking analysis of HSA and S1P was conducted,aiming to predict the key binding pocket do-main of S1P within HSA.Results All pHSA samples exhibited detectable levels of S1P(ranging from 3.31±0.03 to 30.35±0.07 μg/L),with significant variations observed among pHSA samples from different manufacturers(P＜0.001).Conversely,S1P was undetectable in all rHSA samples.Upon load treatment,the binding affinity of HSA from diverse sources to S1P dem-onstrated significant discrepancies(P＜0.001),with rHSA exhibiting approximately double the average S1P loading compared to pHSA(ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L;P＜0.001,t=5.006).Co-culture treatment out-comes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells,while no changes were observed in the supernatant of the blank control group.Notably,significant differences in supernatant S1P concentration were observed among treatment groups at 6 h,12 h,and 24 h(P＜0.001).SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA(KDpHSA-S1P:2.38E-06,KDrHSA-S1P:3.72E-06).Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule.Conclusion HSA from various sources exhibits distinct binding and carrying effects on S1P,which appear to be closely associated with the IB subdomain of the HSA molecule.