Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Objective:To describe the characteristics and change trends of incidence, mortality and disease burden of acute myocardial infarction (AMI) in Qingdao from 2014 to 2020.Methods:We analyzed the incidence data of AMI retrieved from Qingdao Chronic Diseases Surveillance System. The average annual percent change (AAPC) of morbidity and mortality of AMI were evaluated by using Joinpoint log-linear regression model. Disability adjusted life year (DALY) was used to estimate disease burden of AMI in Qingdao.Results:A total of 70 491 AMI cases and 50 832 deaths of AMI occurred in Qingdao from 2014 to 2020. The age-standardized morbidity and mortality were 54.71/100 000 and 36.55/100 000, respectively. During 2014-2020, the AAPC of age-standardized morbidity was 2.86% (95% CI: 0.42%-5.35%), and 4.30% (95% CI: 1.24%-7.45%) in men and 0.78% (95% CI: -0.89%-2.47%) in women, respectively. The log-linear regression model showed that age-standardized morbidity in age groups 30-39, 40-49 years increased rapidly, with the AAPCs of 8.92% (95% CI: 2.23%-16.06%) and 6.32% (95% CI: 3.30%-9.44%), respectively. The trend was also observed in age groups 30-39, 40-49 and 50-59 years in men, with the AAPCs of 11.25% (95% CI: 3.54%-19.54%), 6.73% (95% CI: 2.63%-10.99%) and 6.72% (95% CI: 2.98%-10.60%), respectively. There was no significant change in age-standardized mortality. The DALY rate increased from 7.49/1 000 in 2014 to 8.61/1 000 in 2020, with the AAPC of 1.97% (95% CI: 0.36%-3.60%). Conclusions:The age-standardized morbidity of AMI in men increased in Qingdao, especially in those aged 30-49 years, while age-standardized mortality rate of AMI was relatively stable from 2014 to 2020. The burden of disease of AMI increased in both men and women.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

Objective:To observe the risk factors of acute renal injury(AKI) after coronary artery bypass grafting(CABG) and the influence of blood pressure on AKI.Methods:980 patients in CABG of Cardiology Department of TEDA International Cardiovascular Hospital were diagnosed with AKI according to the AKIN standard, with 706 males and 274 females, averaged(61.9±8.0)years old. Patients were divided into two groups according to whether AKI occurred: AKI group(86 cases) and non AKI group(894 cases). The baseline clinical data, operation related data were compared between the two groups. At the same time, according to the preoperative mean systolic blood pressure(SBP) level, LSP[mean systolic blood pressure<120 mmHg(1 mmHg=0.133 kPa), 374 cases], MSP(mean systolic blood pressure 120-140 mmHg, 481 cases) and HSP(mean systolic blood pressure≥140 mmHg, 125 cases) were classified as covariates, and the influencing factors of dependent variable AKI were analyzed by multivariate logistic regression.Results:The prevalence of AKI was 8.7%(86/980). Compared with non-AKI group, preoperative SBP[(129.8±13.8)mmHg vs.(124.4±13.3)mmHg, P=0.000], mean arterial pressure[(91.9±8.8)mmHg vs.(88.8±9.1)mmHg, P=0.004], and mean pulse pressure[(56.9±10.7)mmHg vs.(53.2±9.8)mmHg, P=0.001]were increased significantly. After adjusted for other risk factors, preoperative SBP elevation, hypertension history, cardiopulmonary bypass(CPB), use of intra-aortic-balloon-pump(IABP), secondary thoracotomy, preoperative diuresis, intraoperative blood transfusion and baseline low glomerular filtration rate(eGFR) were independent risk factors for AKI after CABG. Compared with LSP group, the relative risk of AKI after CABG in HSP group was 2.743(95% CI: 1.595-4.715). In patients with hypertension history, AKI in HSP group was significantly higher than that in LSP group(18.4% vs. 8.1%, P=0.001). However, the preoperative blood pressure level of patients who denied the history of hypertension had no effect on AKI. Conclusion:Preoperative SBP is a risk factor for AKI after CABG. The incidence of AKI after CABG can be significantly reduced by controlling SBP below 140 mmHg in patients with hypertension.

Objective: Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017. Methods: Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza-associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model. Results: The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza-associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza-related excess mortality was higher in people over 75 years old; influenza-associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively. Conclusion Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.

Objective Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017. Methods Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza?associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model. Results The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza?associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza?related excess mortality was higher in people over 75 years old; influenza?associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively. Conclusion Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.

Objective Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017. Methods Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza?associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model. Results The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza?associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza?related excess mortality was higher in people over 75 years old; influenza?associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively. Conclusion Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.

Objective: To observe the effect of acupuncture at points selected from different regions on the positive expression of interstitial cells of Cajal (ICC) and the stem cell factor (SCF) in gastric antrum tissues in diabetic gastroparesis (DGP) rats, and to explore the influence of region-based point selection on the acupoint combination efficacy. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into a normal group (group A), a model group (group B), a group of Zusanli (ST 36) plus Zhongwan (CV 12) (group C), a group of Zusanli (ST 36) plus Neiguan (PC 6) (group D), and a group of Zusanli (ST 36) plus non-meridian non-acupoint points (group E), based on the random number table (n=12). DGP rat model was established by single intraperitoneal injection of 2% streptozotocin and common diet. After successful modeling, the rats were treated once a day for 4 weeks. Positive ICC and SCF expressions were measured by immunohistochemistry. Results: Compared with group A, the gastrointestinal propulsion rate of group B showed a statistically significant decrease (P<0.05). Compared with group B, the gastrointestinal propulsion rate and the expression of ICC in the gastric antrum were significantly higher in group C, group D and group E, and the between-group differences were statistically significant (P<0.05); the expression of C-kit protein in group C was statistically significantly higher than that in group D and group E (P<0.05). The expression of SCF protein was significantly increased in group C than in group B, and the difference was statistically significant (P<0.05). Conclusion: Acupuncture can improve the symptoms of delayed gastric emptying in DGP model rats, and regulate the expression of ICC and SCF in gastric antrum tissues. The effect of Zusanli (ST 36) plus Zhongwan (CV 12) in the gastric region is superior to that of the Zusanli (ST 36) plus distal Neiguan (PC 6) or non-meridian non-acupoint point, indicating that region-based point selection is the key factor affecting the effect of acupoint combination.

Objective To explore the curative effect of warming and dredge the meridian powder of full foot external treatment combined with nursing intervention on grade 0 diabetic foot. Methods A total of 60 patients of grade 0 diabetic foot in our hospital for treatment of type 2 diabetes, were divided into experimental group and control group according to the random number table, each group of 30 cases. The patients of control group received routine treatment and nursing of diabetes, while the patients of experimental group used warming and dredge the meridian powder for full external foot on the basis of the control group. Fasting blood glucose (FBG), 2 h postprandial blood glucose (P2hBG), glycated albumin (GA), ankle brachial index (ABI), electromyogram examination and treatment efficiency were compared before and after the intervention. Results Compared with before treatment, fasting and 2 hour postprandial blood glucose were significantly decreased in both groups, the GA of experimental group declined as well (P<0. 05). After nursing intervention in the experimental group, the improvements of the FBG, P2hBG, ABI, motor nerve conduction and sensory nerve conduction were significantly lower than those of the control group, with statistical significance (P<0. 05). The effect of combined therapy for patients in the experimental group was significantly better than that of the control group (P<0. 05). Conclusions The warming and dredge the meridian powder of full foot external treatment combined with nursing intervention can promote the blood glucose level of patients with diabetic foot and blood glucose fluctuation, and nourish nerve and improve nerve conduction velocity.

Objective The unbalanced phenotype of pe-ripheral blood monocyte is closely related to the pathological progres-sion of pulmonary fibrosis .The present study was designed to address the dynamic changes of circulating monocyte subsets in the experimen-tal mouse model of pulmonary fibrosis , and explore the relationship of circulating monocyte subsets with pulmonary inflammation and fibro-sis. Methods A total of 100male C 57BL/6J mice were random-ized as control group and a bleomycin A 5 group to be treated with sterile saline and bleomycin A5 at 2 mg/kg, respectively.The mice were sacrificed on day 1, 3, 7, 14, and 21 after treatment.The inflammation score and collagen volume fraction ( CVF) of the lung tissue were obtained by HE and Masson staining .The total number and different types of cells in the bronchoalveolar lavage fluid ( BALF) were counted using the routine method .The mRNA expressions of collagens ⅠandⅢwere determined by real-time PCR, the content of hydroxyproline (HYP) assayed by the chloramine-T method, and the proportions of different monocyte subsets measured by flow cytometry . Results Compared with the saline control , the bleo-mycin A5 group showed significantly increases in the inflammation score at 3 and 7 days ( P<0 .01 ) , CVF at 14 and 21 days ( P<0.01), and the numbers of total cells and macrophages in BALF at 3-21 days, the count of neutrophils granulocytes at 1-3 days (P<0.01), The numbers of neutrophile granulocyles were significant higer than that in control groups on the 1st(9.086 ±1.268 vs 1.108 ±0.229), 3rd(5.551 ±0.511 vs 0.315 ±0.100) and 7th(8.093 ±0.922 vs 0.249 ±0.074)day.The mRNA expressions of collagens ⅠandⅢat 14 and 21 days (P<0.05), the content of HYP at 7-21 days (P<0.01), and the proportion of Ly6Chi mon-ocytes on day 1, which peaked on day 3 (P<0.01) and then decreased from day 14 to 21.The proportion of Ly6Chi monocytes was positively correlated with the inflammation score (P<0.000 1) and CVF of the lung tissue (P=0.001 3). Conclusion In the mouse model of bleomycin A5-induced pulmonary fibrosis, dynamic changes of circulating Ly6Chi and Ly6Clo monocyte subsets occurred in different pathophysiological stages .Compared with the pathological process of inflammatory infiltration , Ly6Chi circulating monocytes displayed a rapid response to tissue injury and inflammation .The increased proportion of Ly6Chi monocyte subsets might be closely re-lated with pulmonary inflammation and fibrosis .