1.m6A modification regulates drug-metabolizing enzymes and drug transporters
Shi-Yu ZHAO ; Shuai-Bing LIU ; Yue-Qin WANG ; Xin TIAN
Chinese Pharmacological Bulletin 2024;40(7):1221-1225
N6-methyladenosine(m6A)is the most abundant modification of RNA methylation,dynamically regulated by"writer"and"eraser",regulating the expression of target genes by modulating key biological processes such as mRNA splicing,stability,and translation,after being recognized and combined by"reader".Recent studies have revealed that m6A modifica-tion can regulate the expression of drug-metabolizing enzymes and transporters,consequently affecting the body's drug meta-bolic rate or intracellular drug concentrations,and ultimately in-fluencing therapeutic outcomes.This article reviews the research progress of the molecular mechanism of m6A modification regula-ting drug-metabolizing enzymes and transporters,so as to pro-vide a new idea for rational and personalized clinicaldrug use.
2.Total saponins from Trillium tschonoskii maxim alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis through Keap-1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways
Jian-Hong GAO ; Tian-Ying SONG ; Chao-Xi TIAN ; Fang-Yu ZHAO ; Yi-Duo HE ; Xin LIU ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(10):1850-1857
Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P<0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P<0.01)and increased MDA levels(P<0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P<0.05,P<0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.
3.Clinical value of immature granulocyte percentage in pre-dicting severity of acute appendicitis in children
Xin-Li ZHANG ; Kai-Jiang LI ; Pu-Yu ZHAO ; Liang ZHAO ; Bing LIANG ; Dong-Fang LU ; Yu-Cheng SHI
Chinese Journal of Current Advances in General Surgery 2024;27(7):533-537
Objective:To investigate the clinical value immature granulocyte percentage(IG%)and other inflammatory indicators in the severity of acute appendicitis.Methods:A total of 201 pediatric patients undergoing appendicitis surgery admitted to Zhoukou Central Hospital from June 2022 to August 2023 were included.Patients with pathologically confirmed actue appendici-tis were divided two subgroups:actue simple appendicitis(ASA)group and actue complicated ap-pendicitis(ACA)group,The variables that included IG%,white blood cell(WBC)count,absolute neutrophil count(ANC),absolute lymphocyte count(ALC),neutrophil to lymphocyte ratio(NLR),pro-calcitonin(PCT),C-reactive protein(CRP),platelet to lymphocyte(PLR)and other indexes were ana-lyzed between ASA and ACA group.The logistic regression model for diagnosis of ACA was es-tablished,and the diagostic value of this model and other inflammtory indicators for ACA was evaluated by receiver operating characteristic(ROC)curve analysis.Results:The levels of IG%,WBC,ANC,ALC,NLR,PCT and PLR were higher and the level of ALC was lower in ACA group than those in ASA group(all P<0.05).Logistic regression analysis showed that IG%,NLR and CRP were three diagnostic determinants of ACA(all P<0.05).The AUC of the established logistic model and IG%,NLR,CRP were 0.868,0.821,0.691 and 0.790(all P<0.001).The logistic model was vali-dated by independent cohorts,and the AUC was 0.872,the sensitivity was 90.0%and the speci-ficity was 75.6%.Conlusions:The IG%value can early indicator for pediatric ACA,and the es-tablished logistic regression model based on biomarkers including IG%,NLR and CRP has clinical value in diagnosing ACA in children.
4.Injection of indocyanine green by vasopuncture in fluorescence laparoscopic radical prostatectomy
Wei-Xin ZHANG ; Rong-Jiang WANG ; Yu CHEN ; Ning WANG ; Jian-Xiang YAO ; Bing-Shan XIE
National Journal of Andrology 2024;30(7):604-610
Objective:To investigate the clinical application value of injection of indocyanine green(ICG)via vasopuncture in fluorescence laparoscopic radical prostatectomy(FLRP).Methods:We retrospectively analyzed the clinical data on 50 cases of PCa treated by injection of ICG via vasopuncture in FLRP.The patients were aged(70.60±5.67)years old,with an average PSA value of(18.42±2.69)μg/L.During the operation,we injected ICG at 0.5 ml by vasopuncture through the vas deferens at each side of the scrotum,observed the visualized images of the vas deferens and seminal vesicles using normal high-definition,black-and-white fluorescence,green fluorescence,and color fluorescence respectively,and then isolated the adherent seminal vesicles under the laparoscope.Results:A total of 93 injections of ICG were completed,86 bilaterally,4 on the right and 3 on the left.The vas defer-ens and seminal vesicles were visualized in 41 cases(60 sides,64.52%),19 bilaterally,7 on the right and 15 on the left.Spillage of the fluorescent agent occurred in 9 cases during the incision of the bladder neck and adhesion of the seminal vesicles was found intra-operatively in 10 cases,in which the seminal vesicles were all quickly located by fluorescence visualization.No rectal injury occurred during the surgery.Mild scrotal subcutaneous bruises were observed in 2 cases,with a postoperative pathological Gleason's score of 7.44±0.88.Conclusion:Injection of ICG by vasopuncture is minimally invasive and safe.ICG-mediated near-infrared imaging and real-time fluorescence imaging of the vas deferens and seminal vesicles can achieve precise positioning and removal of the seminal vesicles and prostate gland without causing rectal injury.
5.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
6.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
7.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
8.Assessment of respiratory protection competency of staff in healthcare facilities
Hui-Xue JIA ; Xi YAO ; Mei-Hua HU ; Bing-Li ZHANG ; Xin-Ying SUN ; Zi-Han LI ; Ming-Zhuo DENG ; Lian-He LU ; Jie LI ; Li-Hong SONG ; Jian-Yu LU ; Xue-Mei SONG ; Hang GAO ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(1):25-31
Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60%participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10%participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.
9.Clinicopathologic features of stomach oxyntic gland neo-plasms on 49 patients
Lu-Lu ZHANG ; Hui LI ; Bing-Xin GUAN ; Yu-Ping ZHENG ; Xiao-Lin WU ; Cheng-Jun ZHOU
Chinese Journal of Current Advances in General Surgery 2024;27(1):30-35
Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0~7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100%)and Pepsinogen Ⅰ(83%),focally positive for H+/K+-ATPase(58%).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.
10.Protective role and mechanistic exploration of Irisin in doxorubicin induced-cardiomyopathy
Yu-Ge JIN ; Song-Sen LI ; Hao WANG ; Cai-Ru GUO ; Bing-Bing ZHANG ; Hao-Jie CHEN ; Ya-Xin BAN ; Ru-Bing LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):220-224
Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)%,0,(42.80±6.70)%,(11.74±1.79)%;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)%,(0.5±0.15)%,(38.6±2.39)%,(1.58±0.54)%.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P<0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P<0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

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