Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective To explore the difference in the effectiveness between proximal femoral nail anti-rotation(PFNA)and proximal femoral locking compression plate(PFLCP)of intertrochanteric fracture in the elderly patients combined with knee osteoarthritis.Methods The clinical data of 65 intertrochanteric femoral fractures combined with knee osteoarthritis be-tween June 2015 and February 2021 were retrospectively analyze.They were divided into two groups according to the different surgical methods.PFNA group was composed of 36 patients,12 males and 24 females,aged from 61to 88 years old with an av-erage of(77.0±6.4)years old.There were 17 cases of left injury and 19 cases of right injury.According to modified Evans clas-sification,there were 3 cases of type Ⅱ,19 cases of type Ⅲ,10 cases of type Ⅳ,and 4 cases of type Ⅴ.PFLCP group was com-posed of 29 patients,11 males and 18 females,aged from 60 to 92 years old with an average of(78.8±6.5)years old.There were 14 cases of left injury and 15 cases of right injury.According to modified Evans classification,there were 2 cases of typeⅡ,18 cases of type Ⅲ,7 cases of type Ⅳ,and 2 cases of type Ⅴ.Comparison of operation time,intraoperation blood loss,postoperative bed time,incidence of postoperative complications,Harris score at 6 months and 1 year postoperation.Results All 65 patients were followed up ranging from 12 to 24 months with an average of(16.9±3.6)months.In the PFNA and PFLCP groups,the operation time was respectively(57.6±6.8)min and(77.4±6.5)min,the intraoperative blood loss was(128.3±50.3)ml and(156.3±23.9)ml,postoperative bed time was(4.0±2.5)days and(8.1±2.0)days,Harris score at 6 months post-operative was(45.3±8.6)points and(36.3±7.0)points.There were significant differences between two groups(P＜0.05).Inci-dence of postoperative complications was 19.4％(7/36)and 34.5％(10/29),Harris score at 1 year postoperative was(60.8±6.7)points and(59.0±8.1)points.There was no significant difference between the two groups(P＞0.05).Conclusion Compared with PFLCP,PFNA treatment of elderly patients with knee osteoarthritis between the femoral intertrochanteric fractures shorter surgical time,less intraoperative blood loss,bed rest after surgery,short-term hip function recovery better,when the affected knee joint can tolerate traction,can be used as a priority.

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Objective:To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma(DLBCL)patients with and without hemophagocytic syndrome(HPS).Methods:The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed.The patients were divided into HPS group(15 cases)and non-HPS group(30 cases).The clinical features and prognosis of the two groups were compared,and survival analysis was performed using Kaplan-Meier method.Results:Patients with HSP were mostly characterized by fever,cytopenia and splenomegaly.The levels of ferritin and soluble CD25 increased in all patients.The level of fibrinogen decreased in 66.67％patients,while triglyceride increased in 53.33％patients,and bone marrow hemophagocytosis occurred in 80.00％patients.Compared with non-HSP group,the proportions of patients with advanced stage(Ann Arbor stage Ⅲ/Ⅳ)and lactate dehydrogenase(LDH)≥ 240 U/L were higher in HSP group(both P＜0.05).The median survival time of HSP group was 8.0 months,which was significantly shorter than 45.5 months of non-HSP group(P＜0.001).Conclusion:The DLBCL patients with HPS have later Ann Arbor stage,higher LDH and shorter overall survival time compared with patients without HPS.

Objective:To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma.Methods:The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected,and their clinical characteristics and prognosis were retrospectively analyzed and summarized.Results:The median age of 6 patients was 61(52-74)years old.There were 2 males and 4 females.All patients had fever and abnormal blood routine examination.Physical examination and imaging examination showed no lymphadenopathy,no extranodal lesions in lung,gastrointestinal,liver and spleen,skin,etc.After strict exclusion of systemic lymphoma involvement in the bone marrow,the diagnosis was confirmed by bone marrow examination,5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma(NOS).1 case abandoned treatment,5 cases received CHOP-like or combined R regimen,including 1 case of autologous stem cell transplantation.4 cases died and 2 case survived.The median OS was 5.5(1-36)months.Conclusion:The prognosis of primary marrow lymphoma is poor,and bone marrow-related examination is an important means of diagnosis.Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype,and autologous hematopoietic stem cell transplantation may improve the prognosis.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective:To observe the clinical effect of subretinal injection and intravitreal injection of conbercept in the treatment of polypoid choroidal vasculopathy (PCV).Methods:A prospective, randomized double-blind controlled study. From June 2022 to January 2023, 35 patients of 35 eyes with PCV diagnosed at Affiliated Eye Hospital of Nanchang University were included in the study. All patients were first-time recipients of treatment. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA) were performed in all affected eyes. BCVA was performed using an international standard visual acuity chart and converted to logarithmic minimum resolved angle (logMAR) visual acuity for statistical purposes. Enhanced depth imaging with OCT instrument was used to measure the macular retinal thickness (MRT), subfoveal choroidal thickness (SFCT), and pigment epithelium detachment (PED) height. Randomized numerical table method was used to divide the patients into subretinal injection group (group A) and vitreous cavity injection group (Group B), 18 cases with 18 eyes and 17 cases with 17 eyes, respectively. Comparison of age ( t=0.090), disease duration ( t=-0.370), logMAR BCVA ( t=?0.190), MRT ( t=0.860), SFCT ( t=0.247), and PED height ( t=?0.520) between the two groups showed no statistically significant difference ( P>0.05). The eyes of group A were given one subretinal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg), and subsequently administered on demand (PRN); eyes in group B were given intravitreal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg). The treatment regimen was 3+PRN. Lesions were categorized into active and quiescent according to the results of post-treatment OCT and BCVA. Active lesions were treated with intravitreal injection of conbercept at the same dose as before; stationary lesions were followed up for observation. BCVA and OCT were performed at 1, 2, 3, 6 and 9 months after treatment; ICGA was performed at 3, 6 and 9 months. BCVA, MRT, SFCT, and PED height changes before and after treatment were compared and observed in the affected eyes of the two groups. Independent sample t-test was used to compare between the two groups. Results:With the prolongation of time after treatment, the BCVA of the affected eyes in groups A and B gradually increased, and the MRT, SFCT, and PED height gradually decreased. Compared with group B, at 2, 3, 6, and 9 months after treatment, the BCVA of group A was significantly improved, and the difference was statistically significant ( t=?2.215, ?2.820, ?2.559, ?4.051; P<0.05); at 1, 2, 3, 6, and 9 months after treatment, the MRT of the affected eyes in group A ( t=?2.439, ?3.091, ?3.099, ?3.665, ?5.494), SFCT ( t=?3.370, ?3.058, ?3.268, ?4.220, ?4.121), and PED height ( t=?3.460, ?4.678, ?4.956, ?5.368, ?6.396) were significantly reduced, and the differences were statistically significant ( P<0.05). No complications such as intraocular inflammation, high intraocular pressure, or vitreous hemorrhage occurred in any of the affected eyes during or after treatment. Conclusion:Compared with the intravitreal injection of conbercept, the subretinal injection of conbercept can more effectively reduce the height of MRT, SFCT, PED height, and improve the visual acuity of the affected eyes with PCV.

Objective To study the clinical and pathological characteristics,as well as diagnosis,treatment methods and prognosis of adult patients with chronic active Epstein-Barr virus infection(CAEBVI).Methods Clinical and pathological data of 8 adult patients with CAEBVI admitted to a hospital in Gansu Province from January 2017 to December 2022 were collected retrospectively,clinical and histopathological characteristics,EBV-related test re-sults,as well as treatment and prognosis of patients were analyzed.Results Among 8 CAEBVI patients,3 were males and 5 were females,with the median age of 21.5 years.The median time from onset to diagnosis of CAEBVI was 7 months.The main manifestations were fever,pancytopenia(involving two or three peripheral blood lines),as well as lymph node enlargement,hepatomegaly and splenomegaly.The quantifications of plasma EBV nucleic acid(DNA)were all＞1.0 × 103.The sorting results of EBV infected cells showed that 3 cases were T lymphocytes in-fection,2 were NK cell infection,and 3 were co-infection of T lymphocytes and NK cells.Bone marrow cytological examination of 8 patients showed no atypical lymphocytes,while 6 patients showed hemophagocytic cells.Flow cy-tometey(FCM)typing results showed that no abnormal cell population was detected in all the 8 patients,and no myeloid,B lymphocyte,T lymphocyte and NK cell markers were expressed.The positive rate of T cell receptor(TCR)gene rearrangement was 37.5％(n=3).Histopathology showed that most cases(n=6,75.0％)expressed CD3,partial cases expressed CD4,CD8,CD56,TIA-1,and EBV encoded RNA(EBER),all were positive.The survival rate of patients after treatment was 50.0％(n=4),the follow-up time was 6-51 months,the 1-year sur-vival rate was 85.7％,and the median survival time was 24 months.Conclusion CAEBVI is characterized by varia-ble clinical manifestations that may lead to fatal complications.Early diagnosis and individualized treatment should be performed to reduce mortality of patients.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.