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.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.

Objective To investigate changes of muscle activation in the lower limbs during landing impact as running fatigue pro-gresses. Methods From November to December,2022,eleven male runners were recruited from Wuhan Sports University.They performed a steady-state run at 75%of their maximum heart rate and continued until Borg rating score≥17 or 90%of their maximum heart rate.Muscle activity data were collected using a Delsys wireless surface electromy-ography system,continuously recording the EMG of the quadriceps(vastus medialis,rectus femoris,vastus later-alis),hamstrings(biceps femoris,semitendinosus),gluteus maximus,lateral head of the gastrocnemius and tibia-lis anterior.The pre-activation,post-activation and co-activation characteristics of these lower limb muscles were analyzed. Results With fatigue accumulation during running,significant differences were observed in the pre-activation level of the tibialis anterior among different fatigue points(F=2.955,P=0.048),with the 100%fatigue point showing significantly higher pre-activation levels than the start(P=0.010);as well as post-activation levels of quadriceps(F=6.609,P=0.001),with higher levels at the 100%point compared to the start(P=0.011),33%(P=0.009)and 67%(P=0.043)fatigue points;co-activation ratios of ankle joint during the pre-activation phase(F=3.287,P=0.034),with a significantly higher co-activation ratio at the 100%fatigue point compared to the start(P=0.023). Conclusion As running fatigue accumulates,the central nervous system adjusts the activation levels of various lower limb muscles to modify impact posture,reducing the risk of injury from accumulated lower limb loads.

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 This article aimed to explore the inhibitory effect of β-ionone(BI)on the proliferation of breast canc-er cells through the nuclear factor kappa-B(NF-κB)pathway and its possible mechanism.Methods The methylene blue assay and MTT assay were used to determine the viability of breast cancer cells.The malachite green phosphate assay was used to detect the ac-tivity of protein phosphatase 2A(PP2A).Western blot was used to detect the levels of phosphorylated P65(s534 and s311)(p-P65),PP2A(A,B and C),and phosphorylated ataxia telangiectasia mutant(p-ATM)(s1981)protein.Results BI could significant-ly inhibit the proliferation of human breast cancer BT549 cells and MCF-7 cells in a time-and dose-dependent manner,and the difference was statistically significant(P<0.01).After treated with BI,NF-κB activity was significantly inhibited in MCF-7 cells,as shown by a significant decrease in the level of phosphorylated P65(s311 and s534)protein and an increase in the level of PP2A pro-tein,and the difference was statistically significant(P<0.05).In addition,BI also significantly reduced the phosphorylation of P65 protein and ATM protein in MCF-7 cells by the PP2A inhibitor-okada acid(OA).Conclusion This study shows that BI inhibits the proliferation of breast cancer cells by inhibiting NF-κB activity,and its mechanism may be achieved by increasing PP2A activity to regulate the NF-κB pathway.

Objective:To investigate the phenotypes, molecular types and drug-resistance genes of erythromycin (ERY)-resistant group B Streptococcus (GBS) in pregnant women in late pregnancy in Zhengzhou and provide basic data for the prevention, control and treatment of GBS infection. Methods:This study retrospectively collected 86 GBS strains isolated from the vaginal secretions of pregnant women in late pregnancy at Maternal and Child Health Hospital of Henan Province from 2021 to 2022. ERY-resistant GBS strains were selected using the ERY disk diffusion method, and their susceptibility to 10 different antibiotics was tested. Whole-genome sequencing was performed to analyze their molecular features including molecular types, clonal complex groups and drug-resistance genes. Drug-resistance genes carried by GBS strains belonging to different clonal complex groups were compared.Results:There were 70 ERY-resistant GBS strains. Among them, 7.14%(5/70) exhibited an inducible resistance phenotype to macrolide-lincosamide-streptogramin B (MLSB) antibiotics; 84.29%(59/70) showed constitutive resistance to MLSB antibiotics; 8.57%(6/70) were resistant to macrolides but susceptible to lincosamides. The resistance rates of these strains to clindamycin (CLI), tetracycline (TE) and levofloxacin (LEV) were 91.43%(64/70), 54.29%(38/70) and 60.00%(42/70), respectively. These ERY-resistant strains exhibited multidrug resistance patterns with 40.00%(28/70) showing ERY-CLI-LEV resistance phenotype and 30.00%(21/70) showing ERY-CLI-TE resistance phenotype. The major drug-resistance genes carried by the 70 GBS strains were macrolide/lincosamide resistance genes mreA (100.00%) and ermB (53/70, 75.71%), aminoglycoside resistance genes ant (6)-Ⅰ a (22/70, 31.43%) and aph(3′)-Ⅲ (18/70, 25.71%), and tetracycline resistance genes tetM (22/70, 31.43%) and tetO (13/70, 18.57%). These strains belonged to 12 sequence types derived from seven clonal complexes (CCs) and 48.57%(34/70) of them were clustered into CC12. All CC12 strains harbored ermB, but none carried ermA. The positive rates of lsaE, lunB, and aac (6′)- aph(2" ) in CC19 and CC651 strains, ant (6)-Ⅰ a in CC651 and CC452 strains, and mefA and msrD in CC19 and CC23 strains were significantly higher than those in CC12 strains ( P<0.001). Conclusions:ERY-resistant GBS in Zhengzhou exhibited diverse drug resistance phenotypes and molecular types. CC12 was the most prevalent clonal complex in this region. The constitutive MLSB resistance phenotype and ermB gene were the most common ERY resistance phenotype and genotype, respectively, and tetM gene was related to tetracycline resistance. Furthermore, the drug-resistance genes varied in GBS strains of different clonal complexes. This study suggested that close attention should be paid to the epidemiological situation of GBS in this region and the effectiveness of antibiotics used for clinical prevention and treatment of GBS infection should be carefully evaluated.

Objective:To explore the early prognosis on patient of idiopathic pulmonary fibrosis (IPF) combined with different degrees of pulmonary arterial hypertension (PAH) undertake lung transplantation (LTx).Methods:From January 2017 to December 2020, the clinical data of 134 patients with IPF who underwent LTx in Wuxi People's Hospital were analyzed retrospectively. According to the average pulmonary artery pressure detected by right cardiac catheter before operation, the patients were divided into mild PAH group (63 cases), moderate PAH group (47 cases) and severe PAH group (24 cases). The donor data and the recipient's preoperative, intraoperative and postoperative data were collected; the postoperative survival curve to analyze early survival among the three patient groups.Results:With the increase of pulmonary artery pressure, the rate of abnormal right ventricular function increased, the end diastolic diameter of left ventricle decreased before operation, and the rate of using veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increased during the surgery ( P<0.05). Multivariate analysis found that combined severe PAH had significant effects on primary graft dysfunction (Primary graft dysfunction, PGD), retracheal intubation or tracheotomy, hypovolemic shock within 72 h, and 6-month survival after LTx. The survival surve showed that 30-day survival rates of patients with IPF complicated with mild, moderate and severe PAH were 85.7%, 80.8% and 66.7% respectively, and the 6-month survival rates were 80.9%, 74.0% and 62.2%, respectively. Conclusion:Patient of IPF combined with different degrees of PAH had a significant impact on cardiac function and intraoperative ECMO selection of LTx, and severe PAH could significantly reduce the early survival rate after LTx.

Objective:To compare the effect of extracorporeal membrane oxygenation(ECMO)on pulmonary transplantation(LTx)in patients with idiopathic pulmonary fibrosis(IPF)complicated with pulmonary hypertension(PH).Methods:From January 2017 to December 2020, clinical data were retrospectively reviewed for 112 IPF patients complicated with PH undergoing LTx assisted by venous ECMO(VV-ECMO group, n=68)or venous arterial ECMO(VA-ECMO group, n=44). Gender, age, mechanical ventilation time, oxygenation index, cold ischemic time, preoperative gender, age, smoking history, PO 2, PCO 2, PH degree, NYHA cardiac function grade, right cardiac function, ejection fraction(EF)and complications(hypertension & diabetes)of two groups were compared. Intraoperative approach, operative duration, ECMO transfer time, blood loss, blood transfusion, urine volume, postoperative blood transfusion, mechanical ventilation time, ICU stay time, re-thoracotomy, pulmonary infection, primary graft dysfunction(PGD)and renal insufficiency were recorded. And the effects of two different diversion modes on early postoperative complications and short-term outcomes of LTx were further analyzed by multiple factors. Cox proportional risk model was employed for comparing VV-ECMO and VA-ECMO flow patterns with factors related to recipient survival after transplantation. Results:The preoperative PO 2 of 58.3(51.3, 72.0)mmHg was significantly lower in VV-ECMO bypass group than that of 73.2(63.3, 96.8)mmHg in VA-ECMO group and the difference was statistically significant( P<0.006). Compared with VV-ECMO group, 24(54.5%), 15(34.1%)and 22(50.0%)had NYHA class Ⅲ, severe PH and preoperative right heart enlargement in VA-ECMO group respectively and the differences were statistically significant compared with 17(25.0%), 6(8.8%)and 16(23.5%)in VV-ECMO group( P<0.05 for all). No significant inter-group differences existed in postoperative PGD, postoperative mechanical ventilation time(≥3 d), pulmonary infection, postoperative thoracotomy ratio, postoperative renal insufficiency, ICU stay, hospital stay and other aspects( P>0.05). And 6-month postoperative survival rates of VV-ECMO and VA-ECMO groups were 80.9% and 61.4%, respectively and no significant inter-group difference existed in short-term survival rate(6 months)after adjustment by multivariate Cox regression model( P>0.05). Multivariate statistics indicated that the risk of delayed postoperative withdrawal was 14.452-fold higher in VV-ECMO group than in VA-ECMO group and the inter-group difference was statistically significant(95% CI: 2.448-85.323, P=0.03). Conclusions:No differences exist in postoperative complications or short-term survival rate between IPF recipients with mild PH on VV-ECMO mode and IPF recipients with severe PH on VA-ECMO mode. VV-ECMO flow reversal can delay the transplant back-off time.

Hepatic fibrosis is a pathological process in which the liver is subjected to various acute and chronic injuries for a long time, resulting in activation of hepatic stellate cells, the imbalance between the production and degradation of extracellular matrix, and the deposition of extracellular matrix in the liver, and it is jointly controlled by multiple cellular signal transduction pathways and a series of cellular information molecular networks. If there is no effective treatment, with the progression of the disease, liver fibrous nodules will form, destroy normal liver structure and function, and finally develop into liver cirrhosis, the decline of liver function, and even liver cancer. This article summarizes the research advances in the signaling pathways, receptors, and non-coding RNAs involved in liver fibrosis and the corresponding anti-hepatic fibrosis drugs/molecules.