[Objective] To analyze the infection status of hepatitis E virus (HEV) among blood donors in Zhengzhou, so as to provide data support for formulating local blood screening strategies. [Methods] Random samples from blood donors from January to December 2022 were tested for HEV RNA using PCR technology. Reactive samples were sequenced for gene analysis, and the donors were followed up. [Results] Among 21 311 samples, 3(0.14‰) were reactive for HEV RNA, all of whom were male. Genetic sequencing results revealed that one strong positive sample was genotype 4, while sequencing failed for the other two due to low viral load. A follow-up of 25 strong positive donors showed that ALT significantly increased on day 7 after donation, anti-HEV IgM and anti-HEV IgG turned positive. On day 21, ALT returned to normal, and on day 35, HEV RNA turned negative. Notably, anti-HEV IgM and anti-HEV IgG persisted until day 482. [Conclusion] There is HEV infection among blood donors in Zhengzhou, and it is necessary to expand the screening scope to comprehensively explore the prevalence and genotype distribution of HEV among blood donors.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To investigate the potential value of cerebral glucose metabolism characteristics in anti-leucine-rich glioma-inactivated protein 1 (LGI1) antibody-related encephalitic patients during acute phase as the clinical indicator of disease outcomes.Methods:From October 2019 to December 2023, 28 patients (18 males, 10 females; age (56.6±11.9) year) with anti-LGI1 antibody-related encephalitis diagnosed at Huashan Hospital, Fudan University were prospectively enrolled. All patients received baseline brain 18F-FDG PET imaging and were divided into different subgroups according to the prognosis (good prognosis and poor prognosis groups) and recurrence (recurrence and non-recurrence groups) after follow-up. The difference of Montreal Cognitive Assessment (MoCA) score between the two groups was compared by Mann-Whitney U test. Statistical parametric mapping (SPM) analysis was used to analyze the PET images of different groups by independent-sample t test, and the characteristics of cerebral glucose metabolism of patients with different outcomes were obtained. Results:MoCA scores between the recurrence group ( n=6) and the non-recurrence group ( n=22; 14.0(9.8, 20.5) vs 22.0(18.0, 24.0); Z=2.17, P=0.030), and between the poor prognosis group ( n=13) and the good prognosis group ( n=15; 14.0(10.0, 22.0) vs 22.0(19.8, 25.3); Z=2.47, P=0.013) were significantly different. Compared with the good prognosis group, the cerebral glucose metabolism in the poor prognosis group was decreased in the bilateral frontal lobe, lateral temporal lobe, inferior parietal lobule and cingulate gyrus, but increased in the brainstem, bilateral lentiform nucleus and bilateral paracentral lobule/postcentral gyrus (all t=1.71, all P<0.05). Compared with the non-recurrence group, the metabolism of bilateral medial frontal gyrus, anterior cingulate gyrus, bilateral insula, superior temporal gyrus and thalamus decreased in the recurrence group, while the metabolism of bilateral precentral gyrus, inferior frontal gyrus and bilateral lentiform nucleus increased (all t=1.71, all P<0.05). Conclusion:18F-FDG PET imaging reveals the differences in brain metabolism of anti-LGI1 antibody-related encephalitic patients at baseline with different outcomes (prognosis, recurrence or not), which can provide a new perspective for the clinical evaluation of the disease at baseline.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.

Objective To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease(CKD)and healthy controls.Methods A total of 8 CKD patients admitted in Department of Nephrology of our hospital,and another 5 age-and gender-matched healthy individuals were recruited in this study.Fresh fecal samples were collected from the CKD patients and healthy controls.ITS DNA sequencing was employed to determine the composition of intestinal fungi,and then bioinformatics analysis was applied to compare the differences in fungal community diversity,structure,and function between the 2 groups.Results There were no statistical differences between the 2 groups in terms of age,gender composition,BMI,and so forth.The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups(P＜0.01).So was in the Beta diversity between them(P＜0.01).The relative abundance of Candida was increased significantly(P＜0.01),while those of Cladosporium and Penicillium were decreased in the CKD group(P＜0.05).LEfSe analysis revealed that Candida was significantly enriched in CKD patients,whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.Conclusion The composition of intestinal fungi in CKD patients is different from that in healthy individuals,exhibiting characteristic changes.Dysfunction of gut fungal flora may promote the progression of CKD.Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.

Objective: To investigate the changes in oropharyngeal airway parameters and hyoid position in skeletal ClassⅡ adult female patients with different vertical skeletal types who were treated with maxillary anterior teeth retraction with maximum anchorage, and to provide a reference for orthodontic clinical diagnosis and treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. Sixty adult female patients with skeletal ClassⅡ were selected and divided into a skeletal ClassⅡ normodivergent group and a skeletal ClassⅡ hyperdivergent group based on the patients’ mandibular plane angle. In both groups, the bilateral maxillary first premolars were extracted and the maxillary anterior teeth were retracted with maximum anchorage. Cone beam CT(CBCT) images were collected before and after treatment, and three-dimensional measurement software was used to analyze oropharyngeal airway-related parameters. Results: After retraction of the maxillary anterior teeth with maximum anchorage, the 10 parameters related to the oropharyngeal airway did not exhibit statistically significant differences in the normodivergent group (P>0.05), but the perpendicular distance from the highest point of the hyoid bone to the vertical line passing through the sella (H-X) value decreased (P<0.001). In the hyperdivergent group, the oropharyngeal area at the level of the epiglottis tip (OPA-E), anterior-posterior diameters of the oropharynx at the level of the epiglottis tip (E-AP), most constricted axial area of the oropharynx (OPA-MCA), and anterior-posterior diameters of MCA area of the oropharynx (MCA-AP) decreased after treatment (P<0.001). In addition, the oropharyngeal volume (OPV) decreased after treatment (P<0.05), and the perpendicular distance from the highest point of the hyoid bone to the horizontal line passing through the sella (H-Y) and the highest point of the hyoid bone to the epiglottis base (H-Eb) values increased after treatment (P<0.05). Conclusion After retraction of the maxillary anterior teeth with maximum anchorage, there is no change in the oropharyngeal airway in skeletal ClassⅡ normodivergent female adult patients, while skeletal ClassⅡhyperdivergent female adult patients have a risk of reduction in the oropharyngeal airway after maximuim anchorage retraction of the maxillary anterior teeth.

Objective:To compare the Kadish T staging, AJCC T staging, and Dulguerov T staging system in terms of their impact on surgical treatment selection and survival prognosis in patients with olfactory neuroblastoma (ONB).Methods:The cases of pathologically confirmed ONB from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 were collected and screened. Tumors were staged according to Kadish staging system, AJCC T staging and Dulguerov T staging guidelines. Kaplan-Meier analysis was used to calculate 5-and 10-year overall survival rates for different stages, and the log-rank test was used to detect statistically significant differences. Multivariate analysis was performed using Logistic regression and Cox regression models to explore factors influencing surgical treatment choices and prognosis in ONB patients.Results:A total of 519 ONB patients with complete data available for analysis were included in the study. Multivariate analysis revealed that tumor staging, age, and marital status were closely associated with surgical treatment selection. The 10-year survival rates for patients in stage A, B, and C were 74.1%, 68.7%, 55.0%, respectively. The multivariate analysis failed to show a significant prognostic gradient between adjacent stages in any of the three staging systems.Conclusions:The selection of surgical treatment for ONB is influenced by clinical characteristics such as tumor stage and age. The commonly used Kadish, AJCC T, and Dulguerov T staging systems do not significantly differentiate prognosis between adjacent stages, highlighting the need for the development of a more accurate and comprehensive staging system.