AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS: This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1, 2017, to March 31, 2022. Data on disease duration, age, hypertension, OCT images, central macular thickness(CMT), and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment. Patients were divided into 4 groups according to different types of macular edema: cystoid macular edema(CME), sponge-like diffuse retinal thickening(SDRT), serous retinal detachment(SRD), and mixed type(FULL). Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types, and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS: Totally 139 patients(139 eyes)were classified as having macular edema, including 62 males(44.6%)and 77 females(55.4%), with a mean age of 58.9±10.9 years, and they were divided into 4 groups based on different types of macular edema, including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group, 23 cases(23 eyes; mean age 56.6±10.2 years)in the SDRT group, 22 cases(22 eyes; mean age 57.8±12.0 years)in the SDR group, and 40 cases(40 eyes; mean age 60.0±10.7 years)in the FULL group. There were no significant differences in the duration of disease or age between groups(P>0.05). There was a significant difference in preoperative CMT between groups(P=0.01, one-way ANOVA), with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03). There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26). After conbercept treatment, the macular central recess thickness was reduced and visual acuity was improved in all four groups, among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05), and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05). Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images, in which the efficacy is best in patients with CME but poor in patients with SDRT.

Objective:To investigate the clinical outcomes of lining repair during the reconstruction of nasal defects.Methods:From January 2010 to December 2022, our team treated 15 nasal defect patients aged between 18 and 62 years with an average age of 38, including 8 males and 7 females. The range of the defect was more than one subunit in all cases. And forehead pedicled flaps were chosen for repair. For nasal reconstruction, expander was implanted to expand the central forehead flap. The choice of support depended on the range of the defect, including rib-rib cartilage composite grafts, rib cartilage grafts and ear cartilage grafts. The repair of the lining was selected with the original skin, local nasolabial flapor forehead pedicled flap to repair the mucosal defect of the nose. Postoperative follow-up was conducted to observe the effects.Results:Among the 15 patients, 8 cases underwent rib-rib cartilage composite grafts. 3 cases had rib cartilage grafts, and 4 cases had ear cartilage grafts. All the flaps survived with 1 case experiencing infection. Postoperative follow-up for 0.5 to 2 years showed that the appearance of nasal defects in all 15 cases was significantly improved, with satisfactory results.Conclusions:The repair of nasal defect lining requires a comprehensive analysis based on the specific location, range of the defect, and the selection of the donor area in order to ultimately determine the surgical approach.

To improve the understanding of clinicians on the diagnostic criteria and treatment principlis of pulmonary alveolar proteinosis(PAP),which is a rare respiratory disease.European Respiratory Society published the first edition guidelines for PAP,including a systematic review of the literature and the application of the grading of recommendations,assessment,development and evaluation(GRADE)approach to assess the certainty of evidence and the strength of recommendations.Five questions of patient,intervention,comparison,outcome(PICO)and two narrative questions were developed.Recommendations and evidence-based evidence were given,including management of PAP,whole lung lavage,granulocyte-macrophage colony-stimulating factor(GM-CSF)therapy,rituximab,plasma exchange,and lung transplantation.In addition,recommendations were given for the use of GM-CSF antibody testing,bronchoalveolar lavage,and lung biopsy.This study is to interpret the main content of the guideline.

Ferroptosis is a form of programmed cell death characterized by iron metabolic imbalance and lipid peroxidation.Alzheimer disease(AD)is a neurodegenerative condition.Studies have shown that lipid peroxidation through ferroptosis plays a significant role in the progression of AD.Ferroptosis suppressor protein 1(FSP1)/coenzyme Q10(CoQ10)signaling axis serves as a crucial regulatory element in the process of lipid peroxidation associated with ferropto-sis.This review explores the mechanisms of the FSP1/CoQ10 signaling axis in AD,aiming to present a novel therapeutic ap-proach for AD treatment.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Methods:Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated.Results:A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% –20.5% ), respectively. Conclusion:Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Objective:A genome-wide molecular characterization of FJ21351116, a strain of G3P[8]-E2 2021 collected in Fujian, China, was performed.Methods:Whole genome sequencing of FJ21351116 was performed using a high-sensitivity group A rotavirus whole genome sequencing method. Genomic characteriza-tion of the virus was assessed by nucleic acid sequence analysis using MEGA 11.0, Geneious 9.0.2 and DNASTAR software. Neutralization epitopes of VP7 and VP4 (VP8*) were analyzed using BioEdit v. 7.0.9.0 and PyMOL v. 2.5.2.Results:In this study, FJ21351116 was shown to be a G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype, and the result of phylogenetic tree showed that the VP7, VP4, VP3, and NSP2-NSP5 genes of the FJ21351116 strain were related to the equine-like DS-1-like G3P[8] genes that have been detected in Japan in recent years. VP6, VP1, VP2, and NSP1 genes are closely related to G2P[4] in most countries, especially in Singapore, suggesting that this strain was formed by genetic reassortment during the evolution of equine-like G3P[8] and G2P[4]. Evolutionary relationships between the VP7/VP4 genes of FJ21351116 and Rotarix and RotaTeq vaccines suggest that the multiple mutations in both VP7 and VP4 (VP8*) neutralizing antigenic epitopes and vaccine amino acid sites. It is hypothesized that the Rotarix and RotaTeq vaccines may be less effective against equine DS-1-like G3P[8] RVA, and the sequence differences with Rotarix are higher than those with RotaTeq.Conclusions:In this study, we found a rare case of DS-1-like G3P [8] RVA strain in China. Currently, horse-like DS-1-like G3P [8] RVA is relatively rare in China and may be poorly protected by vaccine strains, emphasizing the importance of continuous monitoring of RVA strains and the development of efficient and full-coverage RVA vaccines.