Hepatic ischemia-reperfusion injury(IRI)is a pathological phenomenon that commonly occurs during liver surgery and transplantation.It leads to serious tissue damage and affects liver function.The mechanisms behind IRI are complex,involving oxida-tive stress,inflammatory responses,and calcium homeostasis disorder.Recently,scientists have paid more attention to the role of endo-plasmic reticulum stress(ERS)in IRI.ERS activates three classical signaling pathways,PERK,IRE1,and ATF6,through the unfolded protein response(UPR),aiming to preliminarily restore endoplasmic reticulum homeostasis and protect cells.However,if the stress re-sponse is excessive or persistent,ERS can activate apoptosis signaling pathways,such as CHOP and Bax/Bak,worsening cell injury.Additionally,ERS is closely related to other cellular stress responses,such as autophagy and oxidative stress,which jointly affect the survival and death of hepatocytes.Regulation of ERS,especially interventions targeting the three UPR pathways,is considered as a po-tential therapeutic pathway for alleviating hepatic IRI.Pharmacological interventions,such as 4-phenylbutyric acid and taurocholic acid,and gene therapies,such as knocking out PERK or IRE1,have shown positive effects in protecting liver function while inhibiting ERS.This paper reviews the mechanism of action of ERS in hepatic IRI,focuses on the specific roles of the three UPR pathways and their potential as therapeutic targets,and explores the future of re-lated therapeutic strategies.

AIM:To investigate the effect of intrinsic specific transforming growth factor-β(TGF-β)signaling on regeneration and repair of myofibers in acute skeletal myositismice model induced by cardiotoxin(CTX).METHODS:One hundred and eighty-six wild C57BL/6 mice and one hundred and thirty-eight mice with conditional knockout of TGF-β receptor 2(TGF-βr2)in myofibers(SM TGF-βr2-/-mice)were selected.CTX injection to anterior tibial muscle(TA)in-duced acute myoinjury in mice.Some SM TGF-βr2-/-mice were given Smad signaling agonist SRI-011381(SRI)intramus-cular injection.All mice were mainly divided into the following groups:control group,SM TGF-βr2-/-group and SM TGF-βr2-/-+SRI group.Twenty-four mice were selected in each group.RT-qPCR and immunofluorescence staining were used to detect the relative mRNA level,protein expression of inflammatory cytokines and low-density lipoprotein receptor-related protein 1(LRP1),respectively,while the relative protein expression of myosin heavy chain 3(MHY3)and embryonic myosine heavy chain(eMHC)in damaged muscle was detected by Western blot and immunofluorescence staining.In vi-tro,after being extracted from neonatal mice,myogenic precursor cells(MPCs)were cultured in an pro-inflammatory mi-lieu and treated with SRI,recombinant mouse extracellular matrix protein 1(rmECM1)alone or in combination.Hereby,they were divided into the following seven groups:control-MPCs group,control-MPCs+LPS group,TGF-βr2-/--MPCs group,TGF-βr2-/--MPCs+LPS group,TGF-βr2-/--MPCs+LPS+SRI group,TGF-βr2-/--MPCs+LPS+rmECM1 group,and TGF-βr2-/--MPCs+LPS+SRI+rmECM1 group.Six mice were selected in each group.RT-qPCR and Western blot were used to detect the relative mRNA level,protein expression of major histocompatibility complex class I molecules(MHC-I/H-2Kb),major histocompatibility complex class II molecules(MHC-II/H2-Eα),Toll-like receptor 3(TLR3),and LRP1.And the relative protein expression of MoyD and myogenin in myotubes was detected by immunofluorescence staining.RE-SULTS:In vivo,compared with control group,SM TGF-βr2-/-group showed the significant upregulation of pro-inflamma-tory cytokines(P<0.05),and the opposite trend of anti-inflammatory cytokines,LRP1,MHY3,eMHC in the injured muscle(P<0.05),with delayed regeneration and repair of myofibers.In vitro,compared with control-MPCs+LPS group,LRP1,MoyD and myogenin significantly downregulated in TGF-βr2-/--MPCs+LPS group,but the downregulation trend was corrected after giving SRI treatment(P<0.05).In addition,compared with the TGF-βr2-/--MPCs+LPS group,the combi-nation of rmECM1 and SRI significantly upregulated the protein expression of MyoD and myogenin(P<0.05).CONCLU-SION:In a mouse model of acute skeletal myositis,intrinsic TGF-β signaling specifically in myofibers regulates local im-mune behavior.It promotes the expression of LRP1 in damaged muscle via Smad2/3 signaling,and LRP1 can then fully bind to ECM1,thereby facilitating muscle regeneration and repair,and improving the prognosis of acute skeletal myositis.

Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P＜0.05),and negatively correlated with the retromolar space(RMS,P＜0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P＜0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P＜0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.

AIM:To investigate the effect of intrinsic specific transforming growth factor-β(TGF-β)signaling on regeneration and repair of myofibers in acute skeletal myositismice model induced by cardiotoxin(CTX).METHODS:One hundred and eighty-six wild C57BL/6 mice and one hundred and thirty-eight mice with conditional knockout of TGF-β receptor 2(TGF-βr2)in myofibers(SM TGF-βr2-/-mice)were selected.CTX injection to anterior tibial muscle(TA)in-duced acute myoinjury in mice.Some SM TGF-βr2-/-mice were given Smad signaling agonist SRI-011381(SRI)intramus-cular injection.All mice were mainly divided into the following groups:control group,SM TGF-βr2-/-group and SM TGF-βr2-/-+SRI group.Twenty-four mice were selected in each group.RT-qPCR and immunofluorescence staining were used to detect the relative mRNA level,protein expression of inflammatory cytokines and low-density lipoprotein receptor-related protein 1(LRP1),respectively,while the relative protein expression of myosin heavy chain 3(MHY3)and embryonic myosine heavy chain(eMHC)in damaged muscle was detected by Western blot and immunofluorescence staining.In vi-tro,after being extracted from neonatal mice,myogenic precursor cells(MPCs)were cultured in an pro-inflammatory mi-lieu and treated with SRI,recombinant mouse extracellular matrix protein 1(rmECM1)alone or in combination.Hereby,they were divided into the following seven groups:control-MPCs group,control-MPCs+LPS group,TGF-βr2-/--MPCs group,TGF-βr2-/--MPCs+LPS group,TGF-βr2-/--MPCs+LPS+SRI group,TGF-βr2-/--MPCs+LPS+rmECM1 group,and TGF-βr2-/--MPCs+LPS+SRI+rmECM1 group.Six mice were selected in each group.RT-qPCR and Western blot were used to detect the relative mRNA level,protein expression of major histocompatibility complex class I molecules(MHC-I/H-2Kb),major histocompatibility complex class II molecules(MHC-II/H2-Eα),Toll-like receptor 3(TLR3),and LRP1.And the relative protein expression of MoyD and myogenin in myotubes was detected by immunofluorescence staining.RE-SULTS:In vivo,compared with control group,SM TGF-βr2-/-group showed the significant upregulation of pro-inflamma-tory cytokines(P<0.05),and the opposite trend of anti-inflammatory cytokines,LRP1,MHY3,eMHC in the injured muscle(P<0.05),with delayed regeneration and repair of myofibers.In vitro,compared with control-MPCs+LPS group,LRP1,MoyD and myogenin significantly downregulated in TGF-βr2-/--MPCs+LPS group,but the downregulation trend was corrected after giving SRI treatment(P<0.05).In addition,compared with the TGF-βr2-/--MPCs+LPS group,the combi-nation of rmECM1 and SRI significantly upregulated the protein expression of MyoD and myogenin(P<0.05).CONCLU-SION:In a mouse model of acute skeletal myositis,intrinsic TGF-β signaling specifically in myofibers regulates local im-mune behavior.It promotes the expression of LRP1 in damaged muscle via Smad2/3 signaling,and LRP1 can then fully bind to ECM1,thereby facilitating muscle regeneration and repair,and improving the prognosis of acute skeletal myositis.

Objective To explore the association between non-high density lipoprotein cholesterol(non-HDL-C)and total MRI burden in cerebral small vessel disease(CSVD)patients.Methods A total of 303 inpatients(≥60 years old)admitted in our department from January 2021 to July 2024 were recruited,and divided into 0-burden score group(108 cases),1-burden score group(61 cases),2-burden score group(66 cases),3-burden score group(35 cases),and≥4-burden score group(33 cases)according to the total CSVD burden.The association between non-HDL-C and to-tal MRI burden was analyzed by binary logistic regression analysis.Results The levels of TC and non-HDL-C were gradually increased with increment of 0-MRI burden score in the 0-,1-,2-,3-and ≥4-burden score groups in turn(P＜0.01).The non-HDL-C level was significantly higher in the 3-than the 0-burden score group(P=0.001),and in the 2-,3-and ≥4-than the 1-burden score group(P＜0.05).The total CSVD MRI burden was positively correlated with the non-HDL-C level(P=0.001).After adjustment of confounding factors such as age,gender,hypertension,dia-betes and hyperlipidemia,non-HDL-C was still an independent risk factor for CSVD(OR=2.869,95％CI:1.012-8.136,P=0.047).Conclusion Higher non-HDL-C is strongly associated with in-creased total CSVD MRI burden in the elderly,and it can serve as an early intervention indicator for CSVD.

Objective To explore the association between non-high density lipoprotein cholesterol(non-HDL-C)and total MRI burden in cerebral small vessel disease(CSVD)patients.Methods A total of 303 inpatients(≥60 years old)admitted in our department from January 2021 to July 2024 were recruited,and divided into 0-burden score group(108 cases),1-burden score group(61 cases),2-burden score group(66 cases),3-burden score group(35 cases),and≥4-burden score group(33 cases)according to the total CSVD burden.The association between non-HDL-C and to-tal MRI burden was analyzed by binary logistic regression analysis.Results The levels of TC and non-HDL-C were gradually increased with increment of 0-MRI burden score in the 0-,1-,2-,3-and ≥4-burden score groups in turn(P＜0.01).The non-HDL-C level was significantly higher in the 3-than the 0-burden score group(P=0.001),and in the 2-,3-and ≥4-than the 1-burden score group(P＜0.05).The total CSVD MRI burden was positively correlated with the non-HDL-C level(P=0.001).After adjustment of confounding factors such as age,gender,hypertension,dia-betes and hyperlipidemia,non-HDL-C was still an independent risk factor for CSVD(OR=2.869,95％CI:1.012-8.136,P=0.047).Conclusion Higher non-HDL-C is strongly associated with in-creased total CSVD MRI burden in the elderly,and it can serve as an early intervention indicator for CSVD.

Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P＜0.05),and negatively correlated with the retromolar space(RMS,P＜0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P＜0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P＜0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.

The Choledochal cyst is an extremely rare congenital anomaly of the bile duct. Early cyst resection and Roux-en-Y hepatojejunostomy are the primary surgical methods for treating choledochal cyst. With the emergence of enhanced recovery after surgery, laparoscopic surgery has effectively reduced the incidence of biliary complications and wound infections, but it still does not meet people's requirements for minimally invasive surgery. Robotic surgery system has the potential to enhance surgical precision and the maneuverability of surgeons due to clear surgical visualization and flexible mechanical arms. The authors review the relevant literatures and conduct a Meta-analysis to evaluate the efficacy of robot-assisted surgery and laparoscopic surgery for choledochal cyst.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.