1.IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKα to attenuate hypercholesterolemia.
Jiaqi LI ; Mingchao WANG ; Kai QU ; Yuyao SUN ; Zequn YIN ; Na DONG ; Xin SUN ; Yitong XU ; Liang CHEN ; Shuang ZHANG ; Xunde XIAN ; Suowen XU ; Likun MA ; Yajun DUAN ; Haibo ZHU
Acta Pharmaceutica Sinica B 2025;15(8):4047-4063
Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N 6-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe -/- and Ldlr -/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.
2.Characteristics of basic research articles published in Chinese Journal of Trauma from 1985 to 2024
Yuqian YAO ; Mingchao ZHANG ; Xiaozhong ZHOU
Chinese Journal of Trauma 2025;41(9):888-893
Objective:To analyze the characteristics of basic research articles published in Chinese Journal of Trauma (hereinafter referred to as the "Journal") from 1985 to 2024. Methods:Data of basic research articles published in the Journal from 1985 to 2024 were retrieved from the Chinese Medical Journal Full-text Database. Excel was used to analyze publication volume, number of cited articles, citation rate, citation frequency, funding support, disciplinary distribution, key words, authors and institutional affiliations within 40 yearsResults:There were 10 687 publications in the Journal within 40 years, among which 617 (5.77%) were basic research articles, comprising 0 article in 1985-2000, 72 articles in 2001-2005, 200 articles in 2006-2010, 231 articles in 2011-2015, 84 articles in 2016-2020, and 30 articles in 2021-2024. Among them, 443 articles were cited, with a citation rate of 71.80% and total citations of 1 465. The average citation count per article was 2.37, with a maximum of 22 citations for a single article. Funded articles accounted for 76.67% (473/617) and showed a marginally higher citation rate (71.88%) compared to non-funded articles (71.53%). The top 4 disciplines by publication volume included orthopedics (203 articles, 32.90%), neurosurgery (119 articles, 19.29%), trauma orthopedics (75 articles, 12.16%), and emergency surgery (24 articles, 3.89%). High-frequency key words included "brain injury","spinal cord injury", "neurons", "stem cell", and "tissue engineering", etc. The first authors mainly came from Chongqing Municipality, Shanghai Municipality, Shandong Province, Jiangsu Province, Zhejiang Province and Tianjin Municipality; 7 authors published more than 2 articles, 3 of whom were from medical institutions in Chongqing Municipality.Conclusion:Over 40-year period, the basic research articles published in the Journal have demonstrated phased fluctuations, interdisciplinary convergence and shift in hotspots (e.g., from neural injury to regenerative medicine), as well as geographical and institutional disparities in contribution.
3.Clinical features and gene variation analysis of aminoacylase-1 deficiency patients caused by ACY1 gene mutation
Mingchao SHI ; Huihui ZHAO ; Zonghui CHEN ; Yuwei HUANG ; Renliang ZHANG ; Qingwen JIN
Chinese Journal of Neurology 2025;58(11):1198-1204
Objective:To investigate the clinical characteristics and genetic variations of patients with aminoacylase-1 deficiency (ACY1D) caused by ACY1 gene mutations, in order to enhance clinicians′ understanding of this rare disease. Methods:Clinical and genetic data of a child with ACY1D admitted to Sir Run Run Hospital, Nanjing Medical University in December 2021 were collected. Using "aminoacylase-1 deficiency" "aminoacylase-1 gene" " ACY1" and "ACY1D" as keywords, relevant cases of ACY1 gene mutations were searched in CNKI, Wanfang Data Knowledge Service Platform, OMIM, and PubMed databases until February 2025. The clinical characteristics and types of genetic variations of previously reported ACY1D patients were summarized and analyzed. Results:The patient was an 8-year and 4-month-old boy. Clinical manifestations included growth retardation, ataxia, and focal epileptic seizures. Increased excretion of various N-acetylamino acids was observed in the urine. Cranial magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing results showed a compound heterozygous mutation in the ACY1 gene: c.1063-1G>A (IVS14-1G>A) and c.170G>A (p.G57D) (reference transcript NM_000666.2), with c.170G>A (p.G57D) being a novel mutation. Family validation results showed that the c.1063-1G>A (IVS14-1G>A) mutation originated from his mother, and the c.170G>A (p.G57D) mutation originated from his father. By literature review 11 English articles were retrieved reporting 18 ACY1D patients, along with the child in this study, totaling 19 cases, with an onset age ranging from 1 week to 4 years and 6 months. Among them, 13/19 patients showed growth retardation, 9/19 patients had language disorders, 8/19 patients had intellectual disabilities, 7/19 patients had ataxia and low muscle tone, 6/19 patients had epilepsy and febrile convulsions, and 3/19 patients had irritability, autism, and muscle weakness. Genetic testing results indicated various types of mutations in the ACY1 gene, including missense, splicing, and frameshift mutations. Conclusions:ACY1D is an autosomal recessive genetic disease caused by ACY1 gene mutations, which is relatively rare in China. The main clinical manifestations include growth retardation, intellectual and language disorders. The c.170G>A heterozygous mutation is a newly discovered variant site, expanding the mutation spectrum of the ACY1 gene. Screening for ACY1 gene variations can aid in achieving a definitive diagnosis..
4.Observation on the 50%effective dose and clinical application of remimazolam in inducing the loss of consciousness in preschool children
Chuikai CHEN ; Mingchao LIANG ; Shitao ZHANG ; Qing WANG ; Yan LI
Chongqing Medicine 2025;54(10):2252-2257
Objective To study the 50%effective dose(ED50)and ED95 of remimazolam in the induc-tion of general anesthesia in preschool children,and to observe its safety and efficacy.Methods Children un-dergoing elective surgery who received endotracheal intubation and general anesthesia from March to October 2024 were selected as the research objects.The ED50 and ED95 of remimazolam were calculated by the modified sequential method.On this basis the additional,the aditional 68 subjects were randomly divided into the remimazolam group(group R,n=34)and the propofol group(group P,n=34).The respiratory rate(RR)and bispectral index(BIS)before induction(T0),1 min(T1)and 3 min(T2)after administration of remima-zolam or propofol in each group were recorded,and the oxygen saturation(SpO2),heart rate(HR)and mean arterial pressure(MAP)at T0,T1,T2,and 1 min after tracheal intubation(T3)were recorded.The success rate of sedation induction,hemodynamic stability and the incidence of adverse reactions such as injection pain,bradycardia,hypotension and panic during induction were compared between the two groups.Results Probit regression analysis showed that the ED50 of remimazolam for inducing loss of consciousness in preschool chil-dren was 0.414 mg/kg,95%CI:0.381-0.448,and the ED95 was 0.474 mg/kg,95%CI:0.443-0.826.The success rate of sedation induction in both groups was 100%.The disappearance time of eyelash reflex in group R was(59.44±5.24)s,which was longer than(29.79±4.04)s in group P(P<0.001).The RR and BIS of group R at T1 and T2 were higher than those of group P,and the HR and MAP of group R at T1,T2 and T3 were also higher than those of group P(P<0.05).The incidence of injection pain,bradycardia and hypoten-sion in group R was lower than that in group P(P<0.05).There was 1 case of panic in group R.Conclusion The ED50 and ED95 of remimazolam for loss of consciousness during general induction in preschool children are 0.414 mg/kg and 0.474 mg/kg respectively.It has a definite sedative effect,stable hemodynamics and a low incidence of adverse reactions for the induction of general anesthesia in this population,demonstrating its suit-ability for clinical use.
5.Hot Melt Extrusion Coupled with 3D Printing Technology in the Development of Ibuprofen Pharmaceutical Cocrystal Preparation
Mingchao YU ; Xue LI ; Wen NI ; Jiaxiang ZHANG
Herald of Medicine 2025;44(6):900-905
Objective To explore the development of new formulations new pharmaceutical cocrystal by combining hot melt extrusion and 3D printing technologies.Methods The insoluble drug ibuprofen and nicotinamide were selected as model drugs,and hot melt extrusion was applied to extrude ibuprofen-nicotinamide cocrystal by regulating the processing temperature,screw speed and residence time,etc.Hot-stage polarized light microscopy,powder X-ray diffraction,differential scanning calorimetry,Fourier transform infrared spectroscopy,and Raman spectroscopy were used for characterization analysis.The process research was carried out by investigating properties such as eutectic particle size and distribution,angle of repose,and vibrational solidity density.On this basis,two 3D printing techniques,fused deposition molding and selective laser sintering type,were selected for pharmaceutical cocrystal loaded sheet printing.Results A new formulation of pharmaceutical cocrystal tablets loaded with ibuprofen-nicotinamide was successfully printed through the combined application of hot-melt extrusion and 3D printing technologies.Conclusions Combined process of hot melt extrusion and 3D printing technology in the field of developing new pharmaceutical cocrystal formulations,laying the material foundation and scientific support for the development of new pharmaceutical cocrystal formulations with personalized and programmable release on demand.
6.Progress in mutual regulation of lncRNA and METTL3 in tumors
Han XU ; Yi ZHANG ; Xin WANG ; Zichen WEI ; Mingchao ZHAO ; Lei PANG
Chinese Journal of Pathophysiology 2025;41(8):1639-1645
Epigenetic modifications of RNA play a crucial role in the initiation and progression of tumors.Among these modifications,N6-methyladenosine(m6A)modification catalyzed by the METTL3 methyltransferase is one of the most common RNA modifications.It is essential for regulating RNA transcription,stability,and translation.At the same time,long non-coding RNAs(lncRNAs)also serve as important regulatory molecules and play a significant role in the development and progression of tumors.However,the reciprocal interaction between lncRNAs and METTL3,as well as their functional mechanisms within tumors,are not fully understood.This paper aims to provide a comprehensive over-view of the mutual regulation between lncRNAs and METTL3 in tumors.The goal is to offer new insights and theoretical foundations for a better understanding of tumor pathogenesis.
7.Super-minimally invasive laparoscopic surgery:technical innovations and clinical research progress
Pan LU ; Lin CHEN ; Yingjie HUANG ; Kai LI ; Mingchao YI ; Dean MU ; Qiang WANG ; Wei ZHANG
Chinese Journal of General Surgery 2025;34(10):2265-2271
With the continuous evolution of minimally invasive surgical concepts,operative techniques are progressively advancing from"minimal injury"toward"scarless"approaches.Super-minimally laparoscopic surgery(SMLS)is a novel surgical modality developed on the basis of conventional laparoscopic techniques through the innovation and recombination of operative elements,aiming to achieve smaller trauma and improved cosmetic outcomes.Utilizing the umbilical skin fold as a natural scar-concealing site,SMLS establishes no more than two primary operating channels(maximum diameter≤15 mm),supplemented by auxiliary ports≤2 mm in diameter on the abdominal wall.Combined with innovative separable surgical instruments and high-definition visualization systems,this approach provides a systematic solution to key issues such as residual access-site scarring.This review summarizes the development,technical innovations,current clinical applications,and potential aesthetic value of SMLS in the evolution of minimally invasive surgery,aiming to offer theoretical insights and research reference for its future promotion and technical refinement.
8.Feasibility and safety of mechanical thrombectomy in the endovascular recanalization of non-acute symptomatic long-segment internal carotid artery occlusion
Lanqi LI ; Chao LI ; Mingchao SHI ; Dajiang XING ; Jie ZHOU ; Feixue YUE ; Kangjia SONG ; Shouchun WANG ; Wenbin ZHANG
Chinese Journal of Cerebrovascular Diseases 2025;22(10):665-676
Objective To explore the safety and feasibility of mechanical thrombectomy as the first-line endovascular strategy in patients with non-acute symptomatic long-segment internal carotid artery occlusion(ICAO)undergoing revascularization.Methods This study retrospectively and consecutively enrolled non-acute symptomatic long-segment ICAO patients treated in the Department of Neurology,First Hospital of Jilin University,between January 2019 and August 2023,with mechanical thrombectomy as the preferred endovascular modality.Baseline and clinical data were collected,including sex,age,stroke-related risk factors(hypertension,diabetes,dyslipidemia,coronary artery disease,prior stroke,smoking and alcohol use history),admission National Institutes of Health stroke scale(NIHSS)score,pre-operative modified Rankin scale(mRS)score,time from last symptom onset to femoral puncture,time from imaging confirmation to femoral puncture,high-resolution MRI,right-sided ICAO,stump morphology(absent,tapered,flat/blunt,irregular),distal backfilling patterns(above ophthalmic segment,cavernous/clinoid segment,below cavernous segment),pathogenesis(atherosclerosis,dissection),types of anesthesia(local,general),procedure time(time frame from femoral puncture to recanalization or final angiography),site of the original occlusion in successfully recanalized cases,surgical techniques(aspiration+balloon angioplasty,aspiration+balloon angioplasty+stent-retriever thrombectomy,aspiration+balloon angioplasty+stent placement,aspiration+balloon angioplasty+stent-retriever thrombectomy+stent placement),stent placement(yes/no),number of stents implanted,and number of cases with retrieved thrombus,observed indicators.Observed indicators including ratio of technical successful recanalization(immediately post-procedure most severely stenosed site stenosis rate<50%,expanded thrombolysis in cerebral infarction[eTICI]grade≥2c),intraoperative complications(distal embolization,symptomatic intracranial hemorrhage,arterial perforation)rate,perioperative mortality rate,30-day stroke recurrence,and 90-day mRS score.Compare the baseline data,clinical data and observational indicators of the patients with successful and unsuccessful recanalization.Base on the original occlusion site,successfully recanalized patients were subclassified into isolated extracranial,isolated intracranial,and tandem lesions patients,and their baseline characteristics and observation indicators were compared.Results(1)A total of 65 patients were enrolled(57 men,8 women;age 39-80 years;median 59[52,65]years)in this study.Technical success was achieved in 52cases(80%).Perioperative complications occurred in 4 patients(6.2%),with 3 distal embolization cases(4.6%),1(1.5%)developed symptomatic intracranial hemorrhage,and no arterial perforations were observed.There was no perioperative mortality.The 30-day stroke recurrence rate was 7.7%(5/65).90-day mRS scores ranged from 0 to 4,with a median of 1.0(0.0,1.5).(2)Baseline and clinical characteristics as well as outcome indicators did not differ significantly between patients with successful versus unsuccessful recanalization in the cohort undergoing mechanical thrombectomy for non-acute symptomatic long-segment intracranial carotid artery occlusion(all P>0.05).(3)Among successfully recanalized patients,17(32.7%)had isolated extracranial lesions,18(34.6%)had isolated intracranial lesions,and 17(32.7%)had tandem lesions.All cases in the extracranial lesions group had original lesion site at the origin of internal carotid artery(C1,17/17).The intracranial group most often had orginal lesion sites at the C4 segment(9/18),whereas tandem lesions predominantly involved C1 plus C4-C5(16/17).Among the three groups,patients with isolated intracranial lesions were younger(57[48,61]years vs.60[52,64],63[58,69]years,P=0.050),and had a lower proportion of right-sided ICAO(4/18 vs.11/17 vs.11/17,P=0.032),while patients with tandem lesions required a greater number of stents(2.0[1.0,2.0]vs.1.0[1.0,1.5],1.0[0.8,2.0],P=0.013).Significant differences were observed in the proportion of patients with retrieved thrombus decreased progressively from patients with isolated extracranial,isolated intracranial to tandem lesions(17/17 vs.17/18 vs.12/17,P=0.024).No significant differences were observed among lesion-site groups with respect to medical history,stump morphology,distal retrograde flow,procedural technique,procedure duration,anesthesia method,or outcome indicators(all P>0.05).Conclusions This study suggested that utilizing mechanical thrombectomy as the first-line endovascular therapy for non-acute symptomatic long-segment ICAO is safe and feasible.The original occlusive sites of non-acute symptomatic long-segment ICAO predominantly involve the cervical origin and the cavernous segment of the internal carotid artery.The conclusions of this study require further validation.
9.Feasibility and safety of mechanical thrombectomy in the endovascular recanalization of non-acute symptomatic long-segment internal carotid artery occlusion
Lanqi LI ; Chao LI ; Mingchao SHI ; Dajiang XING ; Jie ZHOU ; Feixue YUE ; Kangjia SONG ; Shouchun WANG ; Wenbin ZHANG
Chinese Journal of Cerebrovascular Diseases 2025;22(10):665-676
Objective To explore the safety and feasibility of mechanical thrombectomy as the first-line endovascular strategy in patients with non-acute symptomatic long-segment internal carotid artery occlusion(ICAO)undergoing revascularization.Methods This study retrospectively and consecutively enrolled non-acute symptomatic long-segment ICAO patients treated in the Department of Neurology,First Hospital of Jilin University,between January 2019 and August 2023,with mechanical thrombectomy as the preferred endovascular modality.Baseline and clinical data were collected,including sex,age,stroke-related risk factors(hypertension,diabetes,dyslipidemia,coronary artery disease,prior stroke,smoking and alcohol use history),admission National Institutes of Health stroke scale(NIHSS)score,pre-operative modified Rankin scale(mRS)score,time from last symptom onset to femoral puncture,time from imaging confirmation to femoral puncture,high-resolution MRI,right-sided ICAO,stump morphology(absent,tapered,flat/blunt,irregular),distal backfilling patterns(above ophthalmic segment,cavernous/clinoid segment,below cavernous segment),pathogenesis(atherosclerosis,dissection),types of anesthesia(local,general),procedure time(time frame from femoral puncture to recanalization or final angiography),site of the original occlusion in successfully recanalized cases,surgical techniques(aspiration+balloon angioplasty,aspiration+balloon angioplasty+stent-retriever thrombectomy,aspiration+balloon angioplasty+stent placement,aspiration+balloon angioplasty+stent-retriever thrombectomy+stent placement),stent placement(yes/no),number of stents implanted,and number of cases with retrieved thrombus,observed indicators.Observed indicators including ratio of technical successful recanalization(immediately post-procedure most severely stenosed site stenosis rate<50%,expanded thrombolysis in cerebral infarction[eTICI]grade≥2c),intraoperative complications(distal embolization,symptomatic intracranial hemorrhage,arterial perforation)rate,perioperative mortality rate,30-day stroke recurrence,and 90-day mRS score.Compare the baseline data,clinical data and observational indicators of the patients with successful and unsuccessful recanalization.Base on the original occlusion site,successfully recanalized patients were subclassified into isolated extracranial,isolated intracranial,and tandem lesions patients,and their baseline characteristics and observation indicators were compared.Results(1)A total of 65 patients were enrolled(57 men,8 women;age 39-80 years;median 59[52,65]years)in this study.Technical success was achieved in 52cases(80%).Perioperative complications occurred in 4 patients(6.2%),with 3 distal embolization cases(4.6%),1(1.5%)developed symptomatic intracranial hemorrhage,and no arterial perforations were observed.There was no perioperative mortality.The 30-day stroke recurrence rate was 7.7%(5/65).90-day mRS scores ranged from 0 to 4,with a median of 1.0(0.0,1.5).(2)Baseline and clinical characteristics as well as outcome indicators did not differ significantly between patients with successful versus unsuccessful recanalization in the cohort undergoing mechanical thrombectomy for non-acute symptomatic long-segment intracranial carotid artery occlusion(all P>0.05).(3)Among successfully recanalized patients,17(32.7%)had isolated extracranial lesions,18(34.6%)had isolated intracranial lesions,and 17(32.7%)had tandem lesions.All cases in the extracranial lesions group had original lesion site at the origin of internal carotid artery(C1,17/17).The intracranial group most often had orginal lesion sites at the C4 segment(9/18),whereas tandem lesions predominantly involved C1 plus C4-C5(16/17).Among the three groups,patients with isolated intracranial lesions were younger(57[48,61]years vs.60[52,64],63[58,69]years,P=0.050),and had a lower proportion of right-sided ICAO(4/18 vs.11/17 vs.11/17,P=0.032),while patients with tandem lesions required a greater number of stents(2.0[1.0,2.0]vs.1.0[1.0,1.5],1.0[0.8,2.0],P=0.013).Significant differences were observed in the proportion of patients with retrieved thrombus decreased progressively from patients with isolated extracranial,isolated intracranial to tandem lesions(17/17 vs.17/18 vs.12/17,P=0.024).No significant differences were observed among lesion-site groups with respect to medical history,stump morphology,distal retrograde flow,procedural technique,procedure duration,anesthesia method,or outcome indicators(all P>0.05).Conclusions This study suggested that utilizing mechanical thrombectomy as the first-line endovascular therapy for non-acute symptomatic long-segment ICAO is safe and feasible.The original occlusive sites of non-acute symptomatic long-segment ICAO predominantly involve the cervical origin and the cavernous segment of the internal carotid artery.The conclusions of this study require further validation.
10.Characteristics of articles published in Chinese Journal of Trauma from 1985 to 2024
Mingchao ZHANG ; Yuqian YAO ; Xiaozhong ZHOU ; Guodong LIU
Chinese Journal of Trauma 2025;41(9):858-863
Objective:To analyze the characteristics of articles published in Chinese Journal of Trauma (hereinafter referred to as the "Journal") from 1985 to 2024, so as to provide insights for further clarifying its academic orientation and improving its quality. Methods:Data of articles published from 1985 to 2024 in the Journal were retrieved and extracted from the Wanfang Database (retrieval cut-off date: April 10, 2025). Statistical analysis was performed on the publication count, total citation frequency, number of cited articles, number of highly cited articles, proportion of fund-supported articles and their citation rate, distribution of article categories, author distribution, and keyword frequency.Results:Over the 40-year period, the Journal published a total of 10 687 articles, with the total citation frequency of 45 242. Among them, 7 497 articles (70.15%) were cited and 389 (3.64%) were highly cited. A total of 2450 articles (22.93%) were supported by research funds, with a citation rate of 80.29%. The clinical researoh column showed the largest number of publications, accounting for 7 996 articles (74.82%). First authors were distributed across 31 provincial-level regions, contributing 5 878 articles and 29 583 total citations. Thirty-five corresponding authors published more than 30 articles each, 17 of whom were from medical institutions in Chongqing Municipality. A total of 20 686 keywords were identified, with the top 5 being "fracture fixation, internal" (421 times), "craniocerebral injury" (395 times), "diagnosis" (359 times), "brain injury" (354 times), "spinal cord injury" (314 times).Conclusion:Over the 40-year period, the Journal has been characterized by a high overall academic influence despite a relatively low proportion of highly impactful publications, a substantial rate of fund-supported articles, a broad geographical distribution of first authors, with the most significant contributions coming from Chongqing Municipality, and a strong academic foundation in specialized disciplines such as orthopedics and neurosurgery.

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