Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

No case of moyamoya syndrome with bilateral posterior cerebral artery (PCA) occlusion has been reported in China so far as this disease is extremely rare. The case shown in this article is a middle-aged women who has a history of atrial fibrillation, hypertension and type 2 diabetes acutely attacked by this syndrome. The main clinical manifestations included binocular blindness, right limb weakness. Imaging findings showed bilateral acute cerebral infarction in the parietal occipital lobe, bilateral anterior cerebral artery and middle cerebral artery smoke angiogenesis, bilateral PCA occlusion with distal smoke angiogenesis. Considering the medical history of the patient, the cause of the disease was diagnosed as embolic stroke of undetermined source. The patient′s consciousness has been recovered and the limb weakness has been improved after active symptomatic treatment. However, the blindness did not see any improvements. This case report aims to improve clinicians′ understanding of bilateral PCA embolization in patients with moyamoya syndrome so the occurrence of cerebral infarction can be effectively prevented.

Objective:To investigate associations of cerebral perfusion impairment with early neurological deterioration (END) and poor outcome in patients with acute small subcortical infarction (SSI).Methods:Patients with SSI in the perforator artery region admitted to the Department of Neurology, Zhengzhou People's Hospital between January 2020 and November 2022 were prospectively included. END was defined as an increase of ≥2 in the total score of the National Institutes of Health Stroke Scale (NIHSS) or an increase of ≥1 in the motor function score within 72 h after admission. Poor outcome was defined as the modified Rankin Scale score of 2 at 90 d after onset. Cerebral perfusion impairment was defined according to MRI perfusion-weighted imaging parameters. The demographic, baseline clinical and imaging data were collected. Multivariate logistic regression analysis was used to determine associations of cerebral perfusion impairment and END and poor outcome in patients with SSI. Results:A total of 100 patients with SSI were enrolled, including 56 males (56.0%), and aged 69.2±5.8 years. Among them, 19 patients (19.0%) developed END, 27 (27.0%) had poor outcome, and 51 (51.0%) had significant cerebral perfusion impairment. There were statistically significant differences in high sensitivity C-reactive protein, white matter hyperintensities (WMHs) in the basal ganglia, enlarged perivascular space (EPVS) in the basal ganglia, deep cerebral microbleeds (CMBs), and cerebral perfusion impairment between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that higher diastolic blood pressure (odds ratio [ OR] 1.070, 95% confidence interval [ CI] 1.003-1.141); P=0.040], deep WMHs ( OR 2.271, 95% CI 1.135-4.544; P=0.020), deep CMBs ( OR 5.047, 95% CI 1.240-20.549; P=0.024), and cerebral perfusion impairment ( OR 6.083, 95% CI 1.318-28.080; P=0.021) were independent risk factors for END in patients with SSI. There were statistically significant differences in hypersensitive C-reactive protein, NIHSS score at END, basal ganglia EPVS, END, and cerebral perfusion impairment between the poor outcome group and the good outcome group ( P<0.05). Multivariate logistic regression analysis showed that NIHSS score at END ( OR 1.485, 95% CI 1.034-2.133; P=0.032), basal ganglia EPVS ( OR 3.005, 95% CI 1.224-7.378; P=0.016), and cerebral perfusion impairment ( OR 9.234, 95% CI 1.994-42.765; P=0.004) were independent risk factors for the poor outcome at 90 d in patients with SSI, while anterior circulation infarction ( OR 0.066, 95% CI 0.013-0.334; P=0.001) was independently negatively correlated with the poor outcomes at 90 d after onset. Conclusion:Cerebral perfusion impairment is an independent risk factor for END and poor outcome at 90 d after onset in patients with SSI.

Objective　To explore the relevant clinical phenotype of different diseases relating to hot cross bun (HCB) sign and to determine the correlation between neuroimaging and clinical features.Methods　Data of one patient with HCB syndrome in the Department of Neurology of our hospital were collected.The published cases of HCB syndrome were systematically reviewed.According to the etiology,14 cases were analyzed.The clinical symptoms,Magnetic resonance imaging (MRI) features,Laboratory examination treatment and prognosis and so forth were retrospectively analyzed.Results　Published cases through the system references,classify disease and its clinical heterogeneity were reviewed.We found that HCB sign associated with 9 kinds of disease,including nutrition metabolic disease,inflammatory demyelinating disease,nervous system degenerative disease,secondary to suspected vasculitis Parkinson’s syndrome,tumor paraneoplastic disease testicular cancer is caused by the death of infectious diseases,genetic correlation disease related diseases,stroke and poisoning.Conclusion　This study shows that the basic disease spectrum of HCB syndrome may be more extensive than before.According to different clinical phenotypes,imaging features and basic diseases,the occurrence of HCB may be involved in different pathogenesis.

Objective To establish the three-dimensional (3D) finite element model of unicompartmental knee arthroplasty (UKA) with 3° and 7° posterior tibial slope at different knee flexion angles, and to study biomechanical properties and prosthetic wear of the knee joints with two types of posterior tibia slope and their effects on knee function. Methods Combining CT and MRI images of human knee joints with the 3rd-generation Oxford prosthesis, the finite element UKA model with 3° and 7° posterior tibia slope were established. The 1 kN load was applied to center point of the medial and lateral condyles of the femur to simulate the standing load of human body. The maximum stresses and distributions of the prosthesis and articular cartilage at different knee flexion angles were analyzed. ResultsThe maximum stress of the meniscus liner with 3° posterior tibia slope at 0°, 30°, 60°, 90°, 120° knee flexion angles increased by 28.06%, 68.99%, 19.45%, 21.06% and 53.38%, the distribution area was concentrated from the side of the meniscus liner to the central area, and the stress concentration was obvious at 120° knee flexion. The maximum stress of prosthesis with 3° posterior tibia slope was greater than that with 7 ° posterior tibia slope. The expansion of stress concentration area would cause wear and loosening of the prosthesis, contact stress and concentration area of the articular cartilage would subsequently increase with posterior tibia slope increasing, and stress concentration would be more obvious at high knee flexion angles. Conclusions Tibial prosthesis has the higher stress and greater wear under the condition of 3° posterior tibia slope than 7° posterior tibia slope. The research findings provide theoretical basis for the UKA design in clinic.

Objective:To investigate the risk factors for hemorrhagic transformation (HT) in patients with acute posterior circulation ischemic stroke (PCIS) and its impact on outcomes.Methods:From July 2016 to October 2019, patients admitted to the Department of Neurology, the People's Hospital of Zhengzhou and diagnosed as PCIS were enrolled retrospectively. Their demography, clinical data, laboratory and imaging findings were collected. HT was defined as no intracranial hemorrhage detected by the first head CT/MRI after onset, and intracranial hemorrhage was found during head CT/MRI reexamination within 10 d after onset. Symptomatic HT was defined as intracranial hemorrhage indicated by imaging reexamination and the National Institutes of Health Stroke Scale (NIHSS) score was higher than the baseline. The outcome was evaluated by the modified Rankin Scale at 3 months after onset, and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for HT, symptomatic HT, and poor outcomes. Results:A total of 242 patients with PCIS were enrolled. Their age was 68.02±12.0 years, and 111 were females (45.9%). The baseline median NIHSS score was 5.9 (interquartile range: 3.1-8.8). HT occurred in 19 patients (7.9%), and 14 of them (73.7%) were symptomatic HT. Follow-up at 3 months showed that 74 patients (30.58%) had poor outcomes, of which 12 died. Multivariate logistic regression analysis showed that higher baseline systolic blood pressure (odds ratio [ OR] 1.076, 95% confidence interval [ CI] 1.021-1.135, P=0.006; OR 1.161, 95% CI 1.087-1.240, P<0.001) and larger infarct volume ( OR 31.293, 95% CI 4.542-215.592, P<0.001; OR 2.084, 95% CI 1.414-3.073, P<0.001) were the independent risk factors for HT and symptomatic HT. The higher NIHSS score ( OR 1.511, 95% CI 1.307-1.746; P<0.001), diabetes mellitus ( OR 2.041, 95% CI 1.054-3.952; P=0.034) and symptomatic HT ( OR 4.514, 95% CI 1.458-13.979; P=0.009) were the independent risk factors for poor outcomes. Conclusions:HT is rare in patients with PCIS. Higher baseline systolic blood pressure and larger infarct volume are the independent risk factors for HT in patients with PCIS. Higher baseline NIHSS scores, diabetes mellitus, and symptomatic HT are the independent risk factors for poor outcomes in patients with PCIS.

Objective To investigate the protective and therapeutic effect of chalcone ketones compound(code:L2H17,hereinafter referred to as L2)on mice infected with influenza A virus.Methods BALB/c mice were randomly divided into six groups:normal group,model group,positive drug-treated group,L2 treated groups (3 different concentrations).The mice were adapted for 72 hours,before a model was established by intranasal infection.Mice in each group were given medicine by i.g once daily for 6 days starting 24 h before virus challenge.Survival was observed daily for 14 days.The mortality,median survival time,rate of death protection and rate of prolonging life were determined to observe the therapeutic effect of chalcone(L2) against influenza virus infection.The whole lungs were taken under aseptic conditions on days 3 and 5 post-infection to calculat lung indexes and lung index inhibition.The left lung was fixed with 4% formaldehyde for pathological biopsy,the right lung was soaked in RNAstore to detect lung tissue viral load,and the double antibody sandwich ELISA method was used to detect the expression of inflammatory cytokines IL-6 and TNF-α in order to observe the therapeutic effect of L2 on viral pneumonia caused by influenza virus infection.Results Compared with the model group,the L2 80 mg/kg treatment group exhibited significant increases in median survival time(11 d),the rate of death protection (50%),and the rate of prolonging life(24.1%)but a moderate 50% decrease in mortality.In addition,the lung index decreased significantly both on d 3 and 5 after virus infection (P<0.05).The pathological results also improved significantly.The L2 80 mg/kg dose group had a significantly lower viral load of lung tissue on d 3 and 5 post-infection(P<0.05).Compared with model group,the expression of inflammatory factor IL-6 became lower to different degrees.Conclusion L2 has a protective effect on mice infected with influenza virus by reducing the degree of pathological changes of pneumonia caused by influenza viruses.

OBJECTIVETo investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats.

METHODSThe permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp).

RESULTSCompared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected.

CONCLUSIONCapsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Capsaicin ; pharmacology ; Colon ; metabolism ; Fluorescein ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Rhodamine 123 ; pharmacokinetics

Objective To investigate the effect of expression of microRNA-27a(miR-27a) and microRNA-451(miR-451) in A2780/T cells and its relativity to multidrug resistance (MDR)1 mRNA inhibition by procyanidin. Methods Stem-loop PCR method was performed to evaluate the expression of miR-27a and miR-451 in use of procyanidin (0-40μmol/L) in 0-48 h in A2780/T cells. Additionally, over-expressing or interfecting microRNAs by using mimics or inhibitor of miR-27a and miR-451, the expression of MDR1 mRNA was assessed by RT-PCR in cells exposing to procyanidin. Results The expression of miR-27a and miR-451 was significant inhibited by procyanidin in both time- and concentration-dependency. Over-expressed MDR1 mRNA associated with miR-27a or miR-451 mimics was blocked by procyanidin, whereas there was no effect on down-expressed MDR1 mRNA associated with miR-27a or miR-451 inhibitor by procyanidin. Conclusion Procyanidin inhibits MDR1 mRNA expression by inhibiting miR-27a and miR-451 expression in A2780/T cells.

Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.