[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 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.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

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 clinical features and risk factors of primary biliary cholangitis(PBC)comorbid with metabolic associated fatty liver disease(MAFLD)and the interaction between the two diseases.Methods A total of 187 patients who were diagnosed with PBC,MAFLD,or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients,PBC+MAFLD group with 38 patients,and MAFLD group with 79 patients.Related data were collected,including general information,clinical symptoms,serological parameters,transient elastography(FibroScan),and non-invasive fibrosis markers,which were compared between the three groups.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups,the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups,and the binary Logistic regression analysis was used for multivariate analysis.Results There were significant differences between the three groups in sex,age,height,weight,body mass index(BMI),and history of autoimmune diseases(P<0.05).In the PBC+MAFLD group,female patients accounted for 89.5%,with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m2,and in the PBC group,the detection rate of autoimmune diseases was 25.7%(18 patients).There were significant differences between the three groups in the incidence rates of weakness,poor appetite,pruritus,jaundice,varices,ascites,and splenomegaly(all P<0.05).The PBC+MAFLD group had the common symptoms of weakness in 18 patients(47.4%),poor appetite in 15 patients(39.5%),abdominal pain in 14 patients(36.8%),and abdominal distension in 16 patients(42.1%);the MAFLD group had the common symptoms of abdominal pain in 34 patients(43%)and abdominal distension in 32 patients(40.5%);the PBC group had the common symptoms of weakness in 37 patients(52.9%),poor appetite in 25 patients(35.7%),jaundice in 25 patients(35.7%),abdominal pain in 18 patients(25.7%),abdominal distension in 25 patients(35.7%),varices in 19 patients(27.9%),ascites in 23 patients(32.9%),and splenomegaly in 44 patients(62.9%).The PBC+MAFLD group had a controlled attenuation parameter(CAP),which was higher than that of the PBC group,and the PBC group had significantly higher levels of liver stiffness measurement,aspartate aminotransferase-to-platelet ratio index(APRI),and fibrosis-4(FIB-4)than the MAFLD group(all P<0.05).The factors without multicollinearity were included in the regression analysis,and with the PBC group as the reference group,FIB-4(odds ratio[OR]=0.218,95%confidence interval[CI]:0.069-0.633,P<0.05)and history of autoimmune diseases(OR=0.229,95%CI:0.067-0.810,P<0.05)were influencing factors for the onset of PBC with MAFLD;with the MAFLD group as the reference group,ALT(OR=0.157,95%CI:0.025-1.000,P<0.05)and TBil(OR=0.995,95%CI:0.990-0.999,P<0.05)were influencing factors for the onset of PBC with MAFLD.Conclusion PBC with MAFLD lacks specific clinical manifestations,and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation.PBC comorbid with MAFLD may not aggravate the disease progression of PBC.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Atherosclerosis(As)is a chronic inflammatory disease caused by lipid deposition.Panvascular disea-ses,which are mainly caused by As,have gradually attracted the attention of many scholars,and their main pathological features are vascular lesions.Vitamin D plays an important role in anti-As in panvascular diseases.It is involved in the regulation of renin-angiotensin system(RAS),endothelial cell injury,immune response,neutrophil extracellular traps(NET)regulation,apoptosis and autophagy,and is a new target in panvascular diseases research.Traditional Chinese Medicine(TCM)has certain advantages in the prevention and treatment of panvascular diseases.Among them,single herbs,active ingredients and compound prescriptions can regulate vitamin D-related metabolism,and have unique scientific value for the prevention and treatment of As.This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions,aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D.