Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective:To investigate the relationship between adiponectin (ADIPOQ) gene polymorphism and postpartum type 2 diabetes mellitus (T2DM) in pregnant women with gestational diabetes mellitus (GDM).Methods:A retrospective study was conducted on 236 GDM postpartum women admitted to the Affiliated Hospital of Jining Medical College from June 2020 to June 2021 as observation subjects. They were divided into a T2DM group and a non T2DM group based on the occurrence of T2DM after delivery. The clinical data of the two groups were compared. The double deoxygenation end termination method was used to detect the single nucleotide polymorphism (SNP) of the ADIPOQ gene, and the four loci rs17366568, rs822395, rs1501299, and rs2241766 were classified. The relationship between ADIPOQ genotype polymorphism and postpartum T2DM was analyzed using a logistic regression model.Results:The G allele carrying the rs2241766 locus in ADIPOQ gene was negatively correlated with the occurrence of T2DM ( OR=0.71, 0.68, P<0.05). Compared with T2DM patients with TT genotype, the GT+ GG genotype at the rs2241766 locus had a lower risk of occurrence for gestational age ≥2 and HbA 1c>85%. Similarly, T2DM patients with pre pregnancy body mass index (BMI)>25 kg/m 2 were more likely to be carriers of the rs2241766 TT genotype ( P=0.026). The (GT+ TT) genotype carrying the T allele at the rs1501299 locus was a protective factor for gestational age and HbA 1c in T2DM patients. Conclusions:The rs2241766 and rs1501299 polymorphisms of the ADIPOQ gene are associated with susceptibility to postpartum T2DM in GDM women. Individuals with rs2241766 and rs1501299 mutant genotypes belong to the high-risk population for T2DM.

Aim To construct a DC-targeted modified(lacto-N-fucop-entose Ⅲ,LewisX)Pseudomonas aeruginosa(PA)DNA vaccine PLGA nanoparticle(LewisX-PLGA)loading PA PcrV and OprF genes combination,and provide a new idea for the prevention of PA clinical infection.Methods The PLGA nano-particles loading PA PcrV and OprF combined DNA(PLGA+PcrV/OprF)or loading pEGFP(PLGA+pEGFP)were pre-pared by double emulsification-solvent evaporation method.On this basis,the DC-SIGN-targeted ligand LewisX was connected to the surface of PLGA nanoparticles by amide condensation reac-tion.LewisX-modified PLGA-PcrV/OprF(LewisX-PLGA+PcrV/OprF)and LewisX-modified PLGA-pEGFP(LewisX-PL-GA+pEGFP)were prepared.Particle size,Zeta potential,en-capsulation rate and drug loading were evaluated to characterize LewisX-PLGA+PcrV/OprF.The cytotoxicity of LewisX-PLGA+PcrV/OprF was investigated by CCK-8.DC targeting of LewisX-PLGA+pEGFP was validated in vitro transfection.Further,LewisX-PLGA+PcrV/OprF lysosome escape was used to evalu-ate the targeting performance of LewisX-modified PLGA nanopar-ticles loading DNA in vitro.The immunoefficacy of the nanopar-ticles was evaluated by detecting the level of lymphocyte prolifer-ation,humoral immunity and immune protection.Results The diameter of LewisX-PLGA+PcrV/OprF was(201.17±1.6)nm.The encapsulation efficiency of LewisX-PLGA+PcrV/OprF was(85.72±5.3)％.The Zeta potential of LewisX-PLGA+PcrV/OprF was+(31.17±1.8)mV.In the DC2.4 cytotoxici-ty test,the cell survival rates were above 85％.The results of fluorescence microscopy after LewisX-PLGA+pEGFP transfec-tion in vitro showed that LewisX-PLGA+pEGFP was more readi-ly taken up by DC2.4,and LewisX-PLGA+pEGFP had a DC-SIGN specific targeting performance.The CLSM's observation of LewisX-PLGA+Pcrv/OprF showed that more DNA escaped from the lysosome into the cytoplasm.The results suggested that LewisX-PLGA had DC2.4 targeting performance.Because DC2.4 cells endocyted more LewisX-PLGA+Pcrv/OprF into the lysosome,the amount of DNA carried by the nanoparticles esca-ping into the cytoplasm increased.in vivo immune results showed that the lymphocyte proliferation level and antibody titer level of targeted DNA vaccine increased significantly,further improved the survival rate of mice infected with acute pneumoni-a,and reduced the bacterial load of mouse lungs.Conclusions The DC-SIGN-targeted aptamer-modified PA DNA vaccine nanoparticle LewisX-PLGA can be successfully constructed.It promotes the transfection of DNA into DC.It promotes the endo-cytosis of PA DNA vaccine into the DC lysosome and the escape of PA DNA into the cytoplasm.This results in a significant im-mune response in body,which enhances the protective efficacy of vaccine.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.
Phylogeny ; Atractylodes/genetics* ; Genome, Chloroplast ; Whole Genome Sequencing ; Microsatellite Repeats ; Lamiales

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective:To investigate the efficacy, safety and surgical experience of middle meningeal artery embolization using polyvinyl alcohol particle in treating chronic subdural hematoma (CSDH).Methods:A total of 51 CSDH patients (25 accepted first treatment, 19 had invalid atorvastatin treatment, and 7 recurred after burr hole drainage) admitted to Department of Neurosurgery, First Affiliated Hospital of Army Medical University from May 2021 to August 2022 were enrolled. The characteristics of middle meningeal artery were evaluated by three-dimensional time-of-flight (3D TOF) MRA before embolization. With confirmation of no surgical contraindications, unilateral or bilateral embolization of the middle meningeal artery with polyvinyl alcohol particle was performed under local anesthesia. The hematoma recurrence rate and proportion of patients with reduction of maximum hematoma thickness>50% at 2 months after embolization were used as primary outcomes to evaluate the efficacy. Complications and embolization-related adverse events were recorded, and the experiences were retrospectively summarized.Results:For all 51 patients, the characteristics of the middle meningeal artery shown in the preoperative 3D TOF MRA were consistent with those in the intraoperative angiography; 16 patients with unilateral hematoma showed thickened bilateral middle meningeal arteries in preoperative 3D TOF MRA, bilateral blood supply was confirmed by intraoperative angiography and bilateral middle meningeal artery embolization was performed. Interventional embolization was successful in all 51 patients, including unilateral embolization in 19 and bilateral embolization in 32, with a total of 83 sides of embolizations. After embolization, hematoma was absorbed and symptoms improved in 48 patients, and hematoma recurrence was observed in 3 patients (5.9%), with an overall success rate of 94.1%. Excluding the 3 patients with hematoma recurrence, 39 patients completed the 2-month follow-up, and these patients had the maximum hematoma thickness reduction>50%. No mortality, complications or surgery-related adverse events were observed in them.Conclusion:Middle meningeal artery embolization with polyvinyl alcohol particle is safe and effective in treating CSDH; once bilateral middle meningeal artery blood supply is indicated by preoperative MRA in patients with unilateral hematoma, bilateral angiography and embolization should be considered during interventional treatment.

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.