Objective To investigate the predictive factors of progressive motor deficits (PMD) after isolated pontine infarction. Methods Consecutive patients with isolated pontine infarction admitted to hospital within 48 hours after onset were enroled. They were divided into either a PMD group (increase ≥1 within 7 days) or a non-PMD group according to the clinical course and the changes of motor scores of the National Institutes of Health Stroke Scale (NIHSS). The pontine infarction patterns were classified as basal surface infarction and deep infarction, the sides were divided into left and right, the infarct levels were divided into upper, middle, and lower according to diffusion-weighted imaging. The demographics, baseline clinical data, and imaging features were compared between the two groups. Multivariable logistic regression models were used to analyze the predictive factors of PMD after isolated pontine infarction. Results A total of 101 patients with isolated pontine infarction admitted to hospital within 48 h of onset were enroled, including 16 in the PMD group and 85 in the non-PMD group. The proportions of pontine infarction involving the basal surface (87. 5% vs. 47. 1% , χ2 = 8. 851, P = 0. 003), the infarcts on the middle levels (56. 2% vs. 24. 7% , χ2 = 4. 851, P = 0. 028), and basilar artery stenosis or occlusion (62. 5% vs. 27. 1% ,χ2 = 7. 689, P = 0. 006) of the PMD group were significantly higher than those of the non-PMD group, while the proportions of the infarcts on the left sides (18. 8% vs. 56. 5% , χ2 = 7. 664, P = 0. 006) and the infarcts on the upper levels (37. 5% vs. 72. 9% , χ2 = 7. 689, P = 0. 006) of the PMD group was significantly lower than those of the non-PMD group. Multivariate logistic regression analysis identified that pontine infarction involving the basal surface (odds ratio 5. 650, 95% confidence interval 1. 011 - 31. 580, P = 0. 049) and basilar artery stenosis or occlusion (odds ratio 4. 075, 95% confidence interval 1. 127 - 14. 741, P = 0. 032) were the independent risk factors for PMD after isolated pontine infarction. Conclusions Infarction involving the basal surface and basilar artery stenosis or occlusion may be the predictors for PMD after isolated pontine infarction.

Objective: To explore the effect and mechanism of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction. Methods: The acute myocardial infarction (AMI) rat model was established by ligating anterior descending branch of coronary artery for one week.A total of 60 adult male rats in SPF grade with AMI were randomized into the Sacubitril/Valsartan group and the model group, who were gavaged with Sacubitril/Valsartan (68 mg/kg, once daily, n=30) versus with normal saline once daily(n=30) for 4 weeks.Twenty-four hours after the last treatment, the left ventricular cardiac function was examined by echocardiography, and pathological changes of the left ventricle were observed under light microscope.The degree of myocardial fibrosis was quantitatively analyzed by picric acid-sirius scarlet staining.Myocardial cells and fibroblasts from rat pups of the same species were prepared in vitro and were divided into the control group, AngⅡ group, LBQ657 group, valsartan group and LCZ696 group.³[H]-leucine incorporation and ³[H]-proline incorporation were used to detect the myocardial hypertrophy and fibrosis. Results: There was no significant difference in left ventricular function between the the model group and the Sacubitril/Valsartan group before medication (P>0.05). Four weeks after administration of the medications, end-diastolic diameter of left ventricle and end-systolic volume of left ventricle were lower [(9.73±0.26) mm vs.(10.52±0.21) mm, P<0.05; (0.19±0.03) ml vs.( 0.31±0.02) ml, P<0.01], and the left ventricular ejection fraction was higher [(60.17±2.18)% vs.(47.16±5.14)%, P<0.01] in the Sacubitril/Valsartan group than in the model group.The degree of myocardial cell injury in the infarct area was lower, and the area of myocardial fibrosis in the non-infarct zone and peripheral infarcted zone were less in the Sacubitril/Valsartan group than in the model group [(4.0±0.1)% vs. (6.1±0.8)%, P<0.001; (15.7±0.8)% vs. (23.8±1.2)%, P<0.001].³[H]-proline incorporation in cardiac fibroblasts was lower in the Valsartan group than in the Ang Ⅱ group [(152.77±8.46) CPM vs.(221.87±13.41) CPM, P<0.01].³[H]-leucine incorporation in myocardial cells was lower in the Valsartan group than in the Ang Ⅱ group [(113.47±2.33) CPM vs.(127.65±2.38) CPM, P<0.01].³[H]-leucine incorporation in myocardial cells was lower in LBQ657 group than in the Ang Ⅱ group [(119.78±2.98) CPM vs.(127.65±2.38) CPM, P<0.05], and the combined application of valsartan and LBQ657 can further reduce myocardial hypertrophy and fibrosis (P<0.05). Conclusions Sacubitril/Valsartan can effectively alleviate myocardial remodeling and cardiac dysfunction after myocardial infarction, and the mechanism may be related to reducing AngⅡ-induced myocardial hypertrophy and myocardial fibrosis.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.