AIM: To design and construct recombinant epitope nucleotides vaccine of glycoprotein B(gB)and glycoprotein D(gD)of herpes simplex virus type 1(HSV-1), and to investigate its immunoprotective effects and tissue expression in animal models.METHODS: The HSV-1 gB and gD epitope genes were selected and tandem assembled to construct the recombinant protein-coding gene X, which was transducted into the prokaryotic expression vector pET28(a). The recombinant protein was synthesized and utilized to generate monoclonal antibodies, which were subsequently used to immunize New Zealand white rabbits. The immunogenicity of the purified protein and the presence of polyclonal antibodies in the serum were tested through separating serum from cardiac blood, and the serum antibody titers were determined. The pcDNA3.1-X was successfully constructed as a eukaryotic expression vector and immunized the female BALB/c mice aged 4 to 6 wk via intramuscular injection. Serum antibodies and immune-related cytokines were quantified using enzyme-linked immunosorbent assay(ELISA). The expression of the X protein in the ocular, trigeminal ganglion, and brain tissues of the mice was assessed.RESULTS: The target polyclonal antibody was identified with a serum antibody titer of 1:3200 in the rabbit serum after immunized by recombinant protein X. Upon immunizing mice with the eukaryotic recombinant plasmid pcDNA3.1-X, the concentration of HSV-1 serum IgM antibodies of the experimental group was 12.13±0.85 ng/L, which was significantly higher than that of the vector control group(0.49±0.44 ng/L; t=21.07, P<0.001). The concentrations of cytokines interleukin IL-2, IL-4, IL-10, and IFN-γ in the experimental group were 11.63±0.60, 22.65±1.47, 85.75±14.12, and 114.90±6.39 ng/L, respectively, all of which were significantly higher than those in the vector control group and the blank control group(all P<0.05). Immunohistochemical staining revealed the presence of target protein X in the eyeball, trigeminal ganglion, and brain tissue.CONCLUSION: The HSV-1 gB and gD tandem epitope nucleotides vaccine pcDNA3.1-X was successfully constructed, which activates a remarkable immune response and is stably expressed in the eyeball, trigeminal ganglion, and brain tissue. This study provides a foundation for further research of an HSV-1 recombinant antigen epitope tandem vaccine.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

AIM: To evaluate the clinical efficacy of corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking(SC-A-TE-CXL)in the treatment of severe keratoconus.METHODS: Prospective before-after self-control study. A total of 10 cases(14 eyes)of severe keratoconus with the thinnest corneal thickness(including epithelium)less than 400 μm were collected from March 2019 to July 2022 at the ophthalmology department of Affiliated Eye Hospital of Nanjing Medical University. Among them, 8 males(12 eyes)and 2 females(2 eyes)were treated with SC-A-TE-CXL. Corneal curvature, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), the thinnest corneal thickness(TCT), central corneal thickness(CCT), non-contact intraocular pressure, endothelial cell density(ECD)and anterior or posterior elevations at the thinnest point before surgery and at 1, 3, 6 and 12 mo postoperatively were observed and recorded, as well as corneal cross-linking depth at 1 mo postoperatively.RESULTS: UCVA and BCVA at 1, 3, 6, and 12 mo after SC-A-TE-CXL were higher than those preoperatively, but there were no differences(F=0.793, P=0.535; F=0.783, P=0.542). K1, K2, Km and Kmax decreased at each time point postoperatively compared with those preoperatively, but there were no differences(F=0.627, P=0.574; F=1.264, P=0.296; F=0.727, P=0.520; F=1.115, P=0.359). Anterior and posterior elevations at the thinnest point both decreased compared with those preoperatively, but the differences were not statistically significant(F=1.046, P=0.359; F=1.164, P=0.337). The non-contact intraocular pressure at each time point postoperatively was higher than that preoperatively, but the differences were not statistically significant(F=0.814, P=0.522). There were no differences in CCT and TCT at any time points of the follow-ups compared with those preoperatively(F=0.931, P=0.453; F=0.782, P=0.542). There was no difference in ECD at 12 mo postoperatively versus preoperative value(t=1.266, P=0.228). At 1 mo postoperatively, anterior segment optical coherence tomography(AS-OCT)exhibited an increase of density in the anterior stroma, and there was a demarcation line with an average depth of 124.07±25.13 μm.CONCLUSION: SC-A-TE-CXL can be considered as a surgical treatment for severe keratoconus, which can delay the progression of severe keratoconus with high safety. However, the long-term efficacy of this treatment requires further observation.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To explore the safety and effectiveness of catheter aspiration combined with catheterization thrombolysis in the treatment of acute renal infarction(ARI),so as to provide reference for the treatment of this disease.Methods A retrospective analysis was conducted on the clinical and follow-up data of 11 ARI patients treated with catheter aspiration combined with catheter thrombolysis at our hospital during Jan.2019 and Jun.2023.Results Among the 11 patients,upon admission,7 manifested with abdominal pain,5 with lumbar pain,5 with nausea,and 1 with fever.All patients were successfully treated with catheter aspiration combined with catheterization and thrombolysis.After thrombolysis,computed tomography angiography(CTA)showed the renal artery trunk and branch vessels.In 11 patients,the renal artery,branch artery and splenic artery branch vessels were patent.D2 aggregates returned to the normal level 1 month after surgery(＜0.5 mg/L).During the follow-up of 3,6,12 months,no previous symptoms were observed.Ultrasound or CTA showed that the renal artery remained unobstructed.Conclusion The use of catheter aspiration combined with catheter thrombolysis for the treatment of ARI caused by renal artery thrombosis is effective,minimally invasive,and worth clinical promotion.

Bamboo leaf flavonoids(BLF)are compounds extracted from bamboo leaves,possessing properties including antioxidant,antimicrobial and anti-inflammatory properties.This study aimed to investigate the effects of BLF on liver damage,antioxidant function,and related gene expression in rats induced by diquat(DQ).Thirty-two 5-week-old male Sprague-Dawley(SD)rats were randomly divided into four experimental groups:the control group(Con),1 000 mg/kg BLF group(BLF),DQ stress group(DQ),and 1 000 mg/kg BLF+DQ stress group(BLF-DQ).The results showed that compared to the Con,the DQ group exhibited significantly decreased serum AST lev-els(P＜0.05),as well as decreased levels of T-AOC,GPX,SOD,and CAT in the liver(P＜0.05),and increased MDA levels in rats(P＜0.05).Additionally,the gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2 in the liver were significantly reduced(P＜0.05).In contrast,1 000 mg/kg BLF significantly decreased serum AST and ALT levels(P＜0.05),increased levels of T-AOC,GPX,CAT,and SOD in liver(P＜0.05),and significantly increased gene expression of HO-1,GPX,CAT,SOD1,Nrf2,and NQO1(P＜0.05).Compared to the DQ group,BLF-DQ significant-ly decreased liver index(P＜0.05),reduced serum AST and ALT levels(P＜0.05),increased lev-els of CAT,GPX,and T-AOC in liver(P＜0.05),decreased MDA levels(P＜0.05),and signifi-cantly upregulated gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2(P＜0.05).These findings indicated that BLF alleviate liver damage caused by DQ stress in rats,improve liver an-tioxidant function inhibition,activate the Nrf2 signaling pathway and PINK/Parkin mitophagy-re-lated gene expression.

17q12 microdeletion syndrome is a rare genetic disease,commonly characterized by newly occurring mutations,which can cause abnormalities of the urinary and reproductive tract,diabetes mellitus,neurological and psychiatric disorders and mild deformities.This article reports a case of 17q12 microdeletion syndrome with CRYBB2 gene missense mutation,combined with menstrual abnormalities,multiple cysts in both kidneys,hypomagnesemia,hyperuricemia,small pancreatic morphology and low pancreatic enzyme levels.

Objective:To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography.Methods:A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy.Results:The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c. 4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+ PM2_Supporting+ PM5+ PP3+ PP4; PM2_Supporting+ PM3+ PP3+ PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. Conclusion:The FREM2: c. 4537G>A and c. 7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.