The interstitial cells of Cajal (ICC) generate spontaneous pacemaker activities responsible for producing slow waves in the gut smooth muscles. Prostaglandin E2 (PGE2 ) is one of the most important prostanoids in the gut, playing a crucial role in multiple physiological and pathological processes. Because information regarding the effects of PGE2 on colonic ICC is limited, we investigated the effects of PGE2 and its underlying signaling pathways in murine colonic ICC. Whole-cell patch-clamp recordings and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to evaluate the effects of PGE2 on mouse colonic ICC. PGE2 had a dual effect on pacemaker potential in the current-clamp mode. RT-PCR data suggested the expression of EP3 and EP4 receptors in colonic ICC. Low PGE2 concentrations induced membrane depolarization and generation of pacemaker activities. And this effect is mimicked by sulprostone (an EP3 agonist). The low PGE2 concentration-induced effect was inhibited by anoctamin-1 (ANO1) or a T-type Ca2+ channel blocker. Conversely, high PGE2 concentrations induced membrane hyperpolarization and blocked pacemaker potential generation. However, this inhibitory effect was blocked by an ATP-sensitive potassium (K ATP) channel blocker but not by other K+ channel blockers. Low concentrations of PGE2 activated EP3 receptors, leading to excitation of pacemaker activity through regulation of ANO1 and T-type Ca2+ channels in colonic ICC. In contrast, higher concentrations of PGE2 activated EP4 receptors and opened ATP-sensitive K+ channels, resulting in inhibition of pacemaker activity in colonic ICC.

This paper aims to explore the effect of electrical stimulation of triboelectric nanogenerators (TENGs) on the osteogenic and other biological behaviors of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) on titanium surfaces. First, an origami-type TENG was fabricated, and its electrical output performance was tested. The optimal current of the generator and the feasibility of the experiment were verified by the CCK-8 assay and scratch assay. At the optimal current, the osteogenic conditions of the cells in each group were determined by quantitative analysis of the total protein content, alkaline phosphatase (ALP) activity, and alizarin red staining (ARS) on the titanium surface. Finally, the adhesion and spreading of cells on the titanium surface after electrical stimulation were observed. The results showed that the TENG had good electrical output performance, with an open-circuit voltage of 65 V and a short-circuit current of 42 μA. Compared with the rest of the current, a current strength of 30 μA significantly improved cell proliferation and migration, osteogenesis, and adhesion and spreading capabilities. The above results confirm the safety and operability of TENG in biomedical applications, laying the foundation for future TENG applications in reducing the time of bone integration around titanium implants after surgery.
Titanium/chemistry* ; Osteogenesis ; Animals ; Mice ; Osteoblasts/cytology* ; Electric Stimulation/instrumentation* ; Cell Adhesion ; Cell Proliferation ; Surface Properties ; Cell Differentiation ; Nanotechnology

Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective To explore the value of quantitative analysis of perirenal fat combined with Mayo adhesive probability(MAP)score in predicting the WHO/International Society of Urological Pathology(ISUP)nuclear grade of renal cell carcinoma(RCC).Methods The imaging data of 139 pathologically confirmed RCC patients were retrospectively analyzed.The patients were divided into low-grade group(grade Ⅰ-Ⅱ,n=112)and high-grade group(grade Ⅲ-Ⅳ,n=27)according to the WHO/ISUP nuclear grade.Spearman correlation analysis was used to assess the relationship between fat features and WHO/ISUP nuclear grade.The multivariate logistic regression model was used to detemine the related factors of high-grade RCC,and the area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of each parameter.Results The AUC of perirenal adipose tissue(PAT)％alone for evaluating high-grade RCC was the highest,at 0.77[95％confidence interval(CI)0.69-0.83].The stepwise multivariate logistic regression model showed that perinephric fat stranding(PFS)[odds ratio(OR)=34.54,95％CI 7.60-156.87,P＜0.001],PAT％(OR=0.46,95％CI 0.32-0.66,P＜0.001),and tumor location(OR=0.26,95％CI 0.07-0.92,P=0.037)were related factors of high-grade RCC,with an AUC of 0.90(95％CI 0.84-0.94).Conclusion Quantitative analysis of perire-nal fat combined with MAP score can effectively predict the WHO/ISUP nuclear grade of RCC,providing a novel approach for per-sonalized treatment strategies to improve prognosis.

Objective:To explore the effect of fibroblast growth factor 2(FGF2)on ferroptosis of renal fibrotic cells and its po-tential molecular mechanisms.Methods:Rat NRK-52E cells were randomly divided into control group,renal fibrosis model group,FGF2 cytokine stimulation group,knockdown empty plasmid group,si-FGF2 group,overexpression empty plasmid group,overexpres-sion FGF2 group,Fer-1 treatment group.The model group was treated with TGF-β1 to obtain a renal fibrosis cell model.Cellular im-munofluorescence method was used to measure the level of cell fibrosis.Western blot was used to detect ferroptosis-related proteins(Nrf2,GPX4 and SLC7A11)and pathway proteins(STAT3,p-STAT3)expression level in the cells.Results:Knockdown of FGF2 could alleviate the increase in α-SMA and Collagen Ⅲ proteins caused by TGF-β1 stimulation of renal tubular cells(P<0.05).FGF2 could promote the activation of STAT3 protein into p-STAT3.The expression level of SLC7A11 protein was significantly increased after FGF2 cytokine stimulation(P<0.05).Compared with the control group,the expressions of Nrf2 and GPX4 in renal fibrotic cells in the si-FGF2 group and Fer-1 treated group were significantly reduced(P<0.05).In addition,knockdown of FGF2 significantly reduced in-terstitial fibrosis of renal tubular epithelial cells(P<0.05).Conclusion:FGF2 may mediate TGF-β1-induced renal ferroptosis through the STAT3/SLC7A11 signaling pathway,and knock down of FGF2 can improve fibrosis of renal tubular epithelial cells.

Objective:To explore the effect of fibroblast growth factor 2(FGF2)on ferroptosis of renal fibrotic cells and its po-tential molecular mechanisms.Methods:Rat NRK-52E cells were randomly divided into control group,renal fibrosis model group,FGF2 cytokine stimulation group,knockdown empty plasmid group,si-FGF2 group,overexpression empty plasmid group,overexpres-sion FGF2 group,Fer-1 treatment group.The model group was treated with TGF-β1 to obtain a renal fibrosis cell model.Cellular im-munofluorescence method was used to measure the level of cell fibrosis.Western blot was used to detect ferroptosis-related proteins(Nrf2,GPX4 and SLC7A11)and pathway proteins(STAT3,p-STAT3)expression level in the cells.Results:Knockdown of FGF2 could alleviate the increase in α-SMA and Collagen Ⅲ proteins caused by TGF-β1 stimulation of renal tubular cells(P<0.05).FGF2 could promote the activation of STAT3 protein into p-STAT3.The expression level of SLC7A11 protein was significantly increased after FGF2 cytokine stimulation(P<0.05).Compared with the control group,the expressions of Nrf2 and GPX4 in renal fibrotic cells in the si-FGF2 group and Fer-1 treated group were significantly reduced(P<0.05).In addition,knockdown of FGF2 significantly reduced in-terstitial fibrosis of renal tubular epithelial cells(P<0.05).Conclusion:FGF2 may mediate TGF-β1-induced renal ferroptosis through the STAT3/SLC7A11 signaling pathway,and knock down of FGF2 can improve fibrosis of renal tubular epithelial cells.

Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective To explore the value of quantitative analysis of perirenal fat combined with Mayo adhesive probability(MAP)score in predicting the WHO/International Society of Urological Pathology(ISUP)nuclear grade of renal cell carcinoma(RCC).Methods The imaging data of 139 pathologically confirmed RCC patients were retrospectively analyzed.The patients were divided into low-grade group(grade Ⅰ-Ⅱ,n=112)and high-grade group(grade Ⅲ-Ⅳ,n=27)according to the WHO/ISUP nuclear grade.Spearman correlation analysis was used to assess the relationship between fat features and WHO/ISUP nuclear grade.The multivariate logistic regression model was used to detemine the related factors of high-grade RCC,and the area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of each parameter.Results The AUC of perirenal adipose tissue(PAT)％alone for evaluating high-grade RCC was the highest,at 0.77[95％confidence interval(CI)0.69-0.83].The stepwise multivariate logistic regression model showed that perinephric fat stranding(PFS)[odds ratio(OR)=34.54,95％CI 7.60-156.87,P＜0.001],PAT％(OR=0.46,95％CI 0.32-0.66,P＜0.001),and tumor location(OR=0.26,95％CI 0.07-0.92,P=0.037)were related factors of high-grade RCC,with an AUC of 0.90(95％CI 0.84-0.94).Conclusion Quantitative analysis of perire-nal fat combined with MAP score can effectively predict the WHO/ISUP nuclear grade of RCC,providing a novel approach for per-sonalized treatment strategies to improve prognosis.

Bruton's tyrosine kinase(BTK)inhibitors are novel drugs targeted for the treatment of B-cell lymphoma.BTK inhibitors have pro-duced strong curative effects,especially for mantle cell lymphoma(MCL),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SSL),and Waldenstr?m's macroglobulinemia(WM).However,the adverse effect of bleeding has gradually been noted with the wide-spread use of BTK inhibitors in clinical practice.Bleeding events are caused by the off-target effects of BTK inhibitors,which affect platelet function through multiple signaling pathways during use.Bleeding affects patient treatment and threatens their quality of life.As such,the clinical management of bleeding should be strengthened.This paper provides a review of the mechanisms of action and clinical manage-ment of bleeding caused by BTK inhibitors.

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.