Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a variety of motor and non-motor symptoms. Many studies have shown that the transmembrane protein 175 (TMEM175) gene may be a potential target for the treatment of PD and other neurodegenerative disorders, but the specific pathogenic mechanism remains unclear. TMEM175 is a lysosomal protein-coding gene that encodes a lysosomal proton channel protein. This article reviews the research advances in the characterization of the TMEM175 gene and its encoded proteins, the clinical features of mutant PD, and related pathogenic mechanism. It is shown that the TMEM175 gene has an impact on the pathogenesis of PD, and patients with different mutation sites tend to have different ages of onset and clinical features. Compared with the patients without TMEM175 mutations, the patients with TMEM175 mutations tend to have an earlier age of onset, more severe motor symptoms, and more susceptibility to cognitive impairment and non-motor symptoms. This article systematically reviews the TMEM175 gene, in order to assist in the early diagnosis of PD and the discovery of new disease-modifying therapies and treatment strategies.
Parkinson Disease

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

AIM:To investigate the effects of the compound ANBP on wound healing in diabetic rats and ex-plore its mechanism of action.METHODS:Ninety male SD rats were randomly divided into blank,model,compound ANBP,Beifuxin,and nicotinamide mononucleotide(NMN)groups,with 16 rats in each group.Wound healing in each group was observed and samples were taken on days 3,7 and 14 to analyze the wound healing rate.Local histopathological changes were observed using HE and Masson staining.The expressions of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),citrate synthase(CS),isocitrate dehydrogenase(IDH1)and oxoglutarate dehydrogenase(OGDH)were de-tected through immunofluorescence and Western blot.The number and morphology of mitochondria in the wound tissue were observed using transmission electron microscopy.RESULTS:Histomorphological changes revealed significant im-provement in diabetic wound healing in the blank and compound ANBP groups compared to that of the model group.The wound healing rates of the blank,compound ANBP,Beifuxin,and NMN groups were significantly increased on days 3,7,and 14(P<0.01).Compared to the model group,granulation tissue generation was higher in the other groups,cover-ing the wound defect and producing abundant collagen fibers.At 3,7,and 14 days after intervention,the blank,com-pound ANBP,Beifuxin,and NMN groups showed significantly enhanced fluorescence intensities of TCA cycling-related enzymes PDHA1,CS,IDH1,and OGDH indicating increased expression of these enzymes.The levels of the TCA cy-cling-related enzymes were significantly increased(P<0.01)in the compound ANBP,Beifuxin and NMN groups but were significantly decreased(P<0.01)in the model group.An increase in the number and density of mitochondria and a de-crease in the cavitation rate of mitochondria with improved morphology(P<0.05)was observed in the group treated with compound ANBP.CONCLUSION:Compound ANBP may increase the number of mitochondria,improve mitochondrial morphology and function,upregulate the expression levels of PDHA1,CS,IDH1,and OGDH proteins,and accelerate the regeneration of wound granulation tissue,thus promoting the healing of diabetic wounds in rats.

Objective To investigate the value of interleukin(IL)-6 and kidney injury molecule(Kim)-1 in the early prediction of contrast-induced pnephropathy(CIN)after percutaneous coronary intervention(PCI)in patients with coronary heart disease.Methods A total of 730 patients with coronary heart disease who underwent PCI were retrospectively collected,divided into CIN group(n=46)and non-CIN group(n=684),and the medical records of the two groups were compared,and the relationship between Kim-1 and IL-6 of renal injury and CIN was analyzed by binary regression,and the receiver operating characteristic(ROC)curve was used to explore the predictive value of these two markers on CIN after PCI for coronary heart disease.Results There was no significant difference between two groups in terms of preoperative IL-6(P=0.467)and Kim-1(P=0.643),and 48h and 72h after PCI,IL-6 and Kim-1 in CIN group was higher than that in non-CIN group(P＜0.001),and IL-6 and Kim-1 in CIN group was higher than that in before surgery(P＜0.001).48h postoperative IL-6(OR=1.884,P=0.002),48h postoperative Kim-1(OR=1.409,P＜0.001)and 72h postoperative IL-6(OR=1.377,P＜0.001)and 72 hours postoperative Kim-1(OR=1.092,P=0.004)were independent risk factors for CIN.The ROC curve showed that when used as a diagnostic marker for CIN,the area under the curve(AUC)of IL-6(48h),IL-6(72h)were 0.837,0.782,AUC of 48h Kim-1 and 72h Kim-1 were 0.820 and 0.827,respectively.Conclusion IL-6 and Kim-1 are independent risk factors for CIN after PCI for coronary heart disease.IL-6 and Kim-1 were positively correlated with the occurrence of CIN after PCI for coronary heart disease.IL-6 and Kim-1 have good diagnostic sensitivity and specificity for CIN after PCI for coronary heart disease.