This article systematically reviews the role and relationship of heme oxygenase （HO） in the pathogenesis of metabolic associated fatty liver disease （MAFLD） and discusses the biological function of HO， its expression in the liver， its association with lipid metabolism， and its regulatory role in inflammatory reaction and oxidative stress， in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

Objective To investigate the mechanism of action of macrophage-derived exosomes(Exo)in peripheral nerve injury(PNI).Methods Exo were extracted following the polarization of macrophages to either the M1 or M2 phenotype to determine their effects on Schwann cells(SCs),using cell proliferation,quantitative real-time polymerase chain reaction,flow cytometry,RNA sequencing,and Western blot.A sciatic nerve extrusion model was established in vivo.PBS,M1-exo and M2-exo treatment groups were injected with PBS,M1-exo,and M2-exo,respectively,and a separate normal group was set up.The sciatic nerve function index(SFI),wet weight ratio,and staining of neuromuscular tissue were evaluated on a weekly basis in each experimental group following surgical intervention.Results M1-exo facilitated SC migration and upregulated glial-derived nerve growth factor,whereas M2-exo promoted SC proliferation and migration and upregulated brain-derived nerve growth factor and nerve growth factor.The biomarkers,myelin protein zero,glial fibrillary acidic protein,nerve growth factor receptor(NGFR)and S100 calcium-binding protein B(S100)were also detected.In the in vivo experiments,the SFI,wet weight ratio,neuromuscular tissues,and fluorescent areas of nerve axons(marker NF200)and SCs(marker S100)were all significantly better in the M2-exo treatment group at week 4 compared with the PBS treatment group,while there were no significant differences between the M1-exo and PBS treatment groups.Both the in vivo and ex vivo experiments demonstrated that M2-exo facilitated the proliferation of SCs via phosphorylation of the serine/threonine kinase AKT,resulting in downregulation of the cell cycle protein WEE 1.Conclusions M2-exo has been demonstrated to promote up-regulation of genes associated with nerve regeneration by SCs and promote SC proliferation and migration,thereby facilitating nerve regeneration via the AKT-WEE1 pathway.

Objective Based on the concept of quality by design(QbD),to establish the design space of Zhihuang detumescence gel plaster extraction process.Methods With Zhihuang detumescence gel plaster as the model drug,geniposide content and extract yield as critical quality attributes(CQA),failure mode effects analysis(FMEA)combined with fishbone diagram was used to evaluate the risk of extraction process,and single factor experiment was used to determine the critical process parameters(CPPs).The mathematical model of CPPs and CQAs was established by Box-Behnken experimental design,and the design space was obtained and verified by Monte Carlo method.Results The ethanol volume fraction,solvent multiplication and extraction times were determined as CPPs,the mathematical model established by Box-Behnken experimental design was statistically significant at P＜0.05,and combined with the production experience,the resulting operable space was:ethanol volume fraction of 67％-70％,solvent multiplication of 7.5-9 times,and the number of times of extraction was 3 times,Extraction time 1 h.Conclusion The establishment of the extraction process design space of Zhihuang detumescence gel plaster is helpful to improve the quality stability and controllability of the traditional Chinese medicine compound preparation,lay an experimental foundation for the development of subsequent preparations,and provide a reference for the application of the design space method to the compound preparation of traditional Chinese medicine.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

This article systematically reviews the role and relationship of heme oxygenase(HO)in the pathogenesis of metabolic associated fatty liver disease(MAFLD)and discusses the biological function of HO,its expression in the liver,its association with lipid metabolism,and its regulatory role in inflammatory reaction and oxidative stress,in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

Objective To investigate the mechanism of action of macrophage-derived exosomes(Exo)in peripheral nerve injury(PNI).Methods Exo were extracted following the polarization of macrophages to either the M1 or M2 phenotype to determine their effects on Schwann cells(SCs),using cell proliferation,quantitative real-time polymerase chain reaction,flow cytometry,RNA sequencing,and Western blot.A sciatic nerve extrusion model was established in vivo.PBS,M1-exo and M2-exo treatment groups were injected with PBS,M1-exo,and M2-exo,respectively,and a separate normal group was set up.The sciatic nerve function index(SFI),wet weight ratio,and staining of neuromuscular tissue were evaluated on a weekly basis in each experimental group following surgical intervention.Results M1-exo facilitated SC migration and upregulated glial-derived nerve growth factor,whereas M2-exo promoted SC proliferation and migration and upregulated brain-derived nerve growth factor and nerve growth factor.The biomarkers,myelin protein zero,glial fibrillary acidic protein,nerve growth factor receptor(NGFR)and S100 calcium-binding protein B(S100)were also detected.In the in vivo experiments,the SFI,wet weight ratio,neuromuscular tissues,and fluorescent areas of nerve axons(marker NF200)and SCs(marker S100)were all significantly better in the M2-exo treatment group at week 4 compared with the PBS treatment group,while there were no significant differences between the M1-exo and PBS treatment groups.Both the in vivo and ex vivo experiments demonstrated that M2-exo facilitated the proliferation of SCs via phosphorylation of the serine/threonine kinase AKT,resulting in downregulation of the cell cycle protein WEE 1.Conclusions M2-exo has been demonstrated to promote up-regulation of genes associated with nerve regeneration by SCs and promote SC proliferation and migration,thereby facilitating nerve regeneration via the AKT-WEE1 pathway.

Objective Based on the concept of quality by design(QbD),to establish the design space of Zhihuang detumescence gel plaster extraction process.Methods With Zhihuang detumescence gel plaster as the model drug,geniposide content and extract yield as critical quality attributes(CQA),failure mode effects analysis(FMEA)combined with fishbone diagram was used to evaluate the risk of extraction process,and single factor experiment was used to determine the critical process parameters(CPPs).The mathematical model of CPPs and CQAs was established by Box-Behnken experimental design,and the design space was obtained and verified by Monte Carlo method.Results The ethanol volume fraction,solvent multiplication and extraction times were determined as CPPs,the mathematical model established by Box-Behnken experimental design was statistically significant at P＜0.05,and combined with the production experience,the resulting operable space was:ethanol volume fraction of 67％-70％,solvent multiplication of 7.5-9 times,and the number of times of extraction was 3 times,Extraction time 1 h.Conclusion The establishment of the extraction process design space of Zhihuang detumescence gel plaster is helpful to improve the quality stability and controllability of the traditional Chinese medicine compound preparation,lay an experimental foundation for the development of subsequent preparations,and provide a reference for the application of the design space method to the compound preparation of traditional Chinese medicine.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To investigate the effects of early percutaneous coronary intervention (PCI) on myocardial perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) after thrombolysis.Methods:A total of 108 patients with STEMI treated in the Second Hospital of Hebei Medical University from January 2020 to December 2022 were divided into early PCI following thrombolysis group ( n=65) and primary PCI (pPCI) group ( n=43). The general clinical data, and the parameters of routine echocardiography at 1 day after PCI and before discharge were compared between the two groups. Myocardial contrast echocardiography (MCE) was used to evaluate myocardial perfusion at 1 day after PCI and before discharge. Results:There were no significant differences in general clinical data between the early PCI following thrombolysis group and the pPCI group (all P>0.05). The left ventricular ejection fraction (LVEF) in the early PCI following thrombolysis group and pPCI group before discharge was significantly higher than that on the 1st day after PCI(both P<0.05). The difference of LVEF was significant between the early PCI following thrombolysis group and the pPCI group before discharge and 1 day after PCI ( P<0.05). Compared with 1 day after PCI, the global longitudinal strain (LVGLS) of left ventricle increased in early PCI following thrombolysis group and pPCI group before discharge(both P<0.05). The difference of LVGLS between early PCI following thrombolysis group and pPCI group before discharge and 1 day after discharge was statistically significant( P<0.05). There were no significant differences in left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial volume (LAV), ratio of mitral early diastolic velocity to late diastolic velocity (E/A), mean early diastolic velocity of mitral annulus (Em) and E/Em 1 day after PCI and before discharge between early PCI following thrombolysis group and pPCI group (all P>0.05). MCE showed that the MCE score index of early PCI following thrombolysis group and pPCI group before discharge was significantly lower than that of 1 day after PCI(both P<0.001). Compared to the 1 day after PCI, the early PCI following thrombolysis group showed a significant increase in the proportion of normal microvascular perfusion (nMVP) and a decrease in the proportion of delayed microvascular perfusion (dMVP) and microvascular obstruction (MVO) before discharge (all P<0.05). In contrast, the pPCI group demonstrated a significant decrease in the proportion of both nMVP and dMVP before discharge compared to the first day after PCI (all P<0.05). However, the decrease in the proportion of MVO was not statistically significant ( P>0.05). Conclusions:Early PCI following thrombolysis and pPCI can enhance left ventricular systolic function and myocardial perfusion in patients with acute ST-elevation myocardial infarction. Early PCI following thrombolysis may offer additional advantages in improving left ventricular systolic function and myocardial perfusion.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.