This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

AIM: To evaluate the efficacy of phacoemulsification with intraocular lens implantation(PEI)combined with goniosynechialysis(GSL)and goniotomy(GT)under direct vision with gonioscope in the treatment of advanced primary angle-closure glaucoma(PACG)combined with cataract.METHODS: Retrospective case series study. A total of 62 patients(65 eyes)with advanced PACG combined with cataract who were treated in the Second Hospital of Anhui Medical University from December 1, 2021 to March 31, 2023 were enrolled, and they were divided into two groups according to different surgical methods. The control group(32 cases, 33 eyes)received PEI+GSL, whereas the observation group(30 cases, 32 eyes)received PEI+GSL+GT. The intraocular pressure(IOP), best corrected visual acuity(BCVA)and the number of anti-glaucoma medications of the two groups before surgery and at 1 d, 1 wk, 1, 3, and 6 mo after surgery were evaluated. In addition, the visual field, cup-to-disc ratio(C/D), angle open range, anterior chamber depth, and average thickness of retinal nerve fiber layer(RNFL)were evaluated before and 6 mo after surgery.RESULTS: There were significant differences in IOP and lowering range of average IOP at 6 mo between the PEI+GSL+GT group(16.68±2.65, 11.12±8.53 mmHg)and the PEI+GSL group(18.71±2.51, 8.32±4.17 mmHg; P<0.05), and there was no difference in the rate of IOP reduction(44.57%±21.79% and 35.20%±17.94%, P>0.05). The number of anti-glaucoma medications, BCVA, anterior chamber depth, and angle closure range were improved in the two groups at 6 mo after operation(all P<0.01). The number of medication reductions and the range of angle opening at 6 mo after surgery in the PEI+GSL+GT group were significantly higher than those in the PEI+GSL group(P<0.05), and there was no difference in the other indicators between the two groups(all P>0.05). There was no difference in the mean deviation of visual field, C/D and average thickness of RNFL between the two groups at 6 mo after operation compared with those before operation(all P>0.05). The complete surgery success rate of the PEI+GSL+GT group was 81%(26/32), and the conditional success rate was 94%(30/32); while those rates of the PEI+GSL group were 58%(19/33)and 76%(25/33), respectively. There were statistical significance in the success rate of surgery between the two groups(complete success rate χ2=4.275, P=0.039; conditional success rate χ2=4.040, P=0.044). No vision-threatening complications and another surgery occurred in either group.CONCLUSION: The study showed that for patients with advanced PACG with cataract, PEI+GSL+GT is more effective than PEI+GSL.

Objective:To analyze the genetic evolution and molecular characteristics of H7N9 avian influenza virus (AIV) isolated in a live poultry market.Methods:Samples such as poultry feces, sewage, and hair removal machine and chopping board swabs were collected. Real-time fluorescent quantitative PCR was used to detect influenza A virus and H7N9 AIV in the samples. The whole genome of H7N9 AIV was amplified with influenza A virus universal primers and sequenced. BLAST and MEGA X were used for sequence alignment, phylogenetic analysis and molecular characterization.Results:Seven poultry-related environment samples were collected in the live poultry market in Xuchang city in February 2023, and four were positive for H7N9 AIV. The whole genome sequences of three H7N9 AIV isolates were successfully obtained, and the isolates shared high nucleotide identity in different genes (98.37%-100.00%). BLAST analysis showed they were highly identical to H7N9 strains isolated from domestic poultry in China from 2020 to 2021. Genetic evolution analysis showed that the three isolates clustered in the same branch and were closer to the recent environmental isolates than to the recent strains isolated from human or avian. Through comparison with the sequences of the representative strains in different periods, it was found that the isolated strains in this study showed high avian pathogenicity with four amino acids KRAA inserted at the cleavage site; the hemagglutinin receptor-binding site was QSG, which was an avian binding receptor; there was a G186I mutation in hemagglutinin. Mammalian-adaptive mutation E627K was not detected in polymerase basic protein 2. Mutations (R292K and I38T) associated with drug resistance to neuraminidase inhibitor (oseltamivir) and polymerase acidic protein inhibitor (baloshavir) were not detected, suggesting that these isolates remained susceptible to these drugs. A S31N mutation was found in M2 protein, indicating they were resistant to alkamines.Conclusions:The three H7N9 AIV strains isolated in the live poultry market have high avian pathogenicity, but there are no significant increase in mutations related to the binding ability to human receptors, mammalian pathogenicity, viral transmissibility, or drug resistance as compared with previous representative strains causing human or avian infection.

Objective To investigate the mid-and long-term effects of metal-on-metal hip resurfacing arthroplasty (HRA),and to analyze its related factors.Methods A total of 64 patients (81 hips) who underwent metal-on-metal HRA from June 2005 to January 2013 were recruited in the present study.There were 35 males (44 hips) and 29 females (37 hips) with the mean age of 48.26±10.45 years (20-65 years),including 47 unilateral and 17 bilateral HRAs.The cohort consisted of osteoarthritis secondary to the developmental dysplasia of the hip (23 cases,29 hips),necrosis of the femoral head (19 cases,22 hips),osteoarthritis (8 cases,10 hips),rheumatoid arthritis (5 cases,9 hips),ankylosing spondylitis (6 cases,8 hips),pigmented villonodular synovitis (2 cases,2 hips) and Otto's disease (1 case,1 hip).During the follow-up duration,radiographic features,including acetabular inclination angle,stem-femoral shaft angle,component loosening,osteolysis,femoral neck narrowing and heterotopic ossification,were evaluated by hip X-rays in straight and froglike position.The size and type of pseudotumor were assessed by MRI and ultrasonography.Clinical efficacy was evaluated by Harris hip score and the University of California at Los Angeles (UCLA) hip score.Considering revision surgery as the end point,the component survivorship was calculated.Results The mean follow-up was 7.98±2.21 years,ranging from 5.0 to 12.8 years.The mean postoperative Harris hip score (92.01 ±5.69) was higher than the preoperative score (41.93 ±9.09).The mean postoperative UCLA pain,walking,function,activity scores (9.37±0.86,9.14± 1.01,8.77± 1.09,6.47± 1.27,respectively) were improved when compared with the preoperative UCLA scores (3.57± 1.23,5.99± 1.30,5.00± 1.01,3.84± 1.41,respectively).The postoperative flexion,abduction and adduction,medial and lateral rotation of the hip was larger than the preoperative ones.Complications occurred in 10 hips (12.3％,10/81).Seven patients (8 hips) experienced early and intermediate complications,including one intraoperative femoral nerve injury,one deep femoral artery and saphenous nerve injuries during the same surgery,one unexplained pain of hip,one femoral neck fracture,three hips of heterotopic ossification,and one pseudotumour.There were mid-and long-term complications in two hips,including one narrowing of the neck and one pseudotumour which was occurred at 9 years.There was one patient (2 hips) underwent revision surgery twice at 5 months and 9 years.The former cause of revision was femoral neck fracture and the latter one was pseudotumour.The Kaplan-Meier survivorship was 98.8％ at five years,and 95.0％ at ten years.Conclusion Patients who underwent metal-on-metal HRA could obtain good mid and long-term results.Pseudotumour and unexplained pain of the hip are critical factors which can affect the mid-and long-term results and survivorship of metal-on-metal HRA.