Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.

Objective:To analyze the disease burden of colorectal cancer (CRC) among young and middle-aged people in China from 1990 to 2021, and to explore the influence of age, period and cohort on the incidence and mortality of CRC in young and middle-aged people of China.Methods:Data on CRC in patients aged 40-59 years in China from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021 (GBD 2021) database. Statistics such as incidence rate, mortality rate, disability-adjusted life years (DALY), and their corresponding age-standardized rates were calculated to analyze the CRC incidence and mortality in different age and sex groups of young and middle-aged Chinese young people from 1990 to 2021. The Joinpoint regression model was used to analyze the CRC incidence, the mortality and the DALY rate, as well as to calculate the annual percentage change (APC) and the average annual percentage change (AAPC). The effects of three independent factors, namely age, period and cohort, on the incidence and mortality of CRC in young and middle-aged people of China were analyzed and evaluated through the age-period-cohort model.Results:From 1990 to 2021, there was a remarkable upward trend in the incidence, mortality, and DALY of CRC among Chinese young and middle-aged adults. In 2021, the number of incidence cases of CRC among young and middle-aged people in China reached 181 000, and the number of deaths reached 57 900, which were 236.80% and 75.48% higher than those in 1990 (53 800 and 33 000, respectively). During the same period, DALY increased by 62.59%, with the 55-59 age group having the largest increase at 83.35%. From 1990 to 2021, the age-standardized incidence rate (ASIR) increased by 49.04%, rising from 25.51/100 000 to 38.02/100 000, and the age-standardized mortality rate (ASMR) declined by 28.75%, decreasing from 17.01/100 000 to 12.12/100 000, respectively. The increase in ASIR was the greatest among the 40-44 age group, reaching 57.31%, while the decline in ASMR was the most significant among the 50-54 age group, amounting to 30.18%. However, the DALY rate declined by 26.66%, from 673.52/100 000 to 493.94/100 000. The decline in DALY was the greatest among the 50-54 age group, reaching 28.26%. Joinpoint regression model analysis showed that, from 1990 to 2021, the incidence of CRC in Chinese young and middle-aged adults rose on average by 1.32% annually, and the increase was higher in men (1.87%) than that in women (0.36%). The mortality rate showed a downward trend, with an average annual decline of 1.10%, with a higher decline in women than in men (-2.14% vs. -0.50%). The DALY rate showed a downward trend, with an average annual decline of 1.00%, and more decline in women than in men (-2.06% vs. -0.41%). All of these trends were statistically significant (all P<0.001). The age-period-cohort model analysis showed that, the net drift of CRC incidence was 1.21% (1.02%-1.41%) per year among Chinese young and middle-aged adults between 1990 and 2021, while the net drift in mortality was -1.40% (-1.59%--1.21%) per year. The impact of age on CRC incidence and mortality intensified with advancing age. Incidence attributable to age rose from 12.66% (11.90%- 13.46%) in the 40-44 age group to 56.68% (54.37%-59.08%) in the 55-59 age group. Similarly, mortality attributable to age increased from 6.47% (6.12%-6.85%) in the 40-44 age group to 25.74% (24.58%-26.96%) in the 55-59 age group. In all age groups, the role of CRC incidence and mortality attributable to age was higher in men than in women. Period effects on the RR value of CRC incidence showed a declining trend followed by an upward trend, with the highest risk during 2015-2019 ( RR=1.36, 95% CI: 1.28-1.43), using 2000-2004 as the reference. For mortality, period effects exhibited a declining trend, with the highest risk during 1990-1994 ( RR=1.23, 95% CI: 1.15-1.32), using 2000-2004 as the reference. Cohort effects indicated that later birth cohorts had higher incidence risks, with the highest incidence observed in the 1973-1977 birth cohort ( RR=1.30, 95% CI: 1.16-1.45), using the 1953-1957 birth cohort as the reference. Conversely, later birth cohorts had lower mortality risks, with the lowest mortality in the 1973-1977 birth cohort ( RR=0.78, 95% CI: 0.69-0.88), using the 1953-1957 birth cohort as the reference. Conclusions:From 1990 to 2021, the changes in the disease burden of CRC among young and middle-aged people in China are manifested as an increase in standardized incidence rate and a decrease in standardized mortality rate. Meanwhile, there are gender differences in the trend of temporal changes. Age, period and cohort all have a significant impact on the incidence and mortality trends of colorectal cancer in young and middle-aged people. Research on the etiology of CRC should be strengthened, and targeted prevention and control strategies should be formulated.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Objective: To evaluate the effect of exercise prescription intervention among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for guiding appropriate physical activity and glycemic control in this population. Methods: In July 2023, T2DM patients managed by two community health service centers in Qingjiangpu District, Huai'an City, Jiangsu Province, were selected as the study participants and randomly assigned divided into a control group and an intervention group. The control group received routine chronic disease management under the basic public health services, while the intervention group, in addition to receiving the same routine chronic disease management, was provided with exercise prescription to guide their physical activity at baseline (T0), after 3 months of intervention (T1), and after 6 months of intervention (T2). Data on weight-related indicators, glycated hemoglobin (HbA1c), and blood lipid were collected through physical examinations and laboratory tests at T0 and after 12 months of intervention (T3). The differences in indicators between the two groups before and after the intervention were analyzed using generalized estimating equations. Results: The intervention group consisted of 197 patients, including 99 males, accounting for 50.25%. The median disease duration was 7.10 (interquartile range, 7.80) years, and 113 patients had suboptimal HbA1c levels, accounting for 57.36%. The control group included 196 patients, including 99 females, accounting for 50.51%. The median disease duration was 6.10 (interquartile range, 7.00) years, and 100 patients had suboptimal HbA1c levels, accounting for 51.02%. Before the intervention, no statistically significant differences were observed between the two groups in gender, educational level, disease duration, pharmacological treatment, smoking, alcohol consumption, and HbA1c levels (all P>0.05). In the intervention group, the proportion of participants engaging in aerobic exercise and strength training increased from 78.17% and 8.12% at T0 to 85.79% and 16.24% at T3, respectively (both P<0.05). The results of the generalized estimating equations revealed significant interactions between group and time for waist-to-hip ratio, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) following the intervention (all P<0.05). A statistically significant difference in waist-to-hip ratio was found between the two groups (P<0.05), with a greater reduction observed in the intervention group compared to the control group. Significant differences in TC and LDL-C levels were noted across different intervention time points (both P<0.05). Specifically, the intervention group demonstrated reductions of 0.35 mmol/L in TC and 0.42 mmol/L in LDL-C from baseline to follow-up (both P<0.05). Conclusion The 12-month exercise prescription intervention can effectively enhance exercise participation and reduce waist-to-hip ratio, TC, and LDL-C levels among patients with T2DM.

OBJECTIVES: Urinary calculi are characterized by a high recurrence rate, and patients' adherence to self-management after discharge directly affects health outcomes. Traditional offline follow-up models often face problems such as poor compliance and uneven allocation of medical resources, making it difficult to meet individualized health management needs. Remote follow-up provides a novel solution to optimize long-term management, improve health literacy, and enhance clinical outcomes. This study aims to evaluate the effect of remote follow-up under an intelligent medical collaborative model on quality of life and health-promoting lifestyle in patients with urinary calculi, and to assess its short-term impact on clinical outcomes. METHODS: A total of 118 patients with urinary calculi admitted to a tertiary hospital in Hunan Province between August and November 2024 were recruited and randomly assigned to a control group (n=59) or an intervention group (n=59). The control group received routine departmental follow-up, while the intervention group underwent remote follow-up based on an intelligent medical collaborative model for one month. Assessments were conducted before discharge (T0), 15 days after discharge (T1), and one month after discharge (T2), using the Wisconsin Stone Quality of Life Questionnaire and the Health-Promoting Lifestyle Profile. At T2, the incidence of forgotten ureteral stents (FUS), ureteral stent-related complications, unplanned readmissions, and patient satisfaction were evaluated. RESULTS: No significant differences were observed between groups at T0 in baseline characteristics or outcome measures (all P>0.05). At T1 and T2, the intervention group had significantly higher health-related quality of life scores than the control group (P<0.05). Generalized estimating equation (GEE) analysis showed significant between-group effects (Wald's χ²=22.961, P<0.001), time effects (Wald's χ²=23.065, P<0.001), and interaction effects (Wald's χ²=6.930, P<0.05). Similarly, at T1 and T2, the intervention group scored significantly higher on health-promoting lifestyle than the control group (P<0.05), with significant between-group effects (Wald's χ²=22.936, P<0.001), time effects (Wald's χ²=10.694, P<0.001), and interaction effects (Wald's χ²=18.921, P<0.05). No significant differences were found between groups in the incidence of FUS, ureteral stent-related complications, or unplanned readmissions (all P>0.05). Patient satisfaction was significantly higher in the intervention group (t=4.089, P<0.001). CONCLUSIONS Remote follow-up under an intelligent medical collaborative model helps improve quality of life, promote health-oriented lifestyles, and enhance patient satisfaction among individuals with urinary calculi.
Humans ; Quality of Life ; Male ; Female ; Urinary Calculi/therapy* ; Health Promotion/methods* ; Middle Aged ; Adult ; Follow-Up Studies ; Treatment Outcome

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

BACKGROUND:Our previous studies found that decreased expression of connexin 43 and its Ser368 phosphorylation after myocardial hypothermic ischemia-reperfusion was closely associated with decreased cardiac conduction velocity and reperfusion arrhythmia.OBJECTIVE:To observe the effect of changes in membrane-type matrix metalloproteinase 2,matrix metalloproteinase 2 and collagen type Ⅳ on the expression of connexin 43 and its Ser368 phosphorylation and electrical conduction in the myocardial extracellular matrix after hypothermic ischemia-reperfusion.METHODS:Sixteen Langendorff extracorporeal cardiac perfusion models were successfully established from SD rats and randomly divided into a control group(n=8)and a hypothermic ischemia-reperfusion group(n=8).The control group was balanced perfused with 37 ℃ Krebs-Henseleit solution for 15 minutes and then continued to be perfused with 37 ℃ Krebs-Henseleit solution for 90 minutes.The hypothermic ischemia-reperfusion group was balanced perfused with 37 ℃ Krebs-Henseleit solution for 15 minutes,and then the heart was arrested for 60 minutes by injection of 4 ℃ Thomas solution.During the cardiac arrest,the periphery was protected by 4 ℃ Krebs-Henseleit solution.Half-volume 4 ℃ Thomas solution was reperfused 30 minutes after the arrest.After stopping the arrest,the heart was reperfused with 37 ℃ Krebs-Henseleit solution for 30 minutes.The occurrence of arrhythmias,rebeating time,and the duration of arrhythmias were recorded from the immediate time point to the end of the reperfusion period.Conduction velocity,absolute inhomogeneity,and inhomogeneity index were measured using the Mapping Lab multi-channel electrophysiological mapping system at the time of balanced perfusion for 15 minutes(T1),reperfusion for 15 minutes/continuous perfusion for 90 minutes(T2),and reperfusion for 30 minutes/continuous perfusion for 105 minutes(T3).The relative expression levels of membrane-type matrix metalloproteinase 2,matrix metalloproteinase 2,collagen type Ⅳ,connexin 43,and its Ser368 phosphorylation in ventricular tissue were detected by western blot assay.RESULTS AND CONCLUSION:(1)No arrhythmia occurred in the control group.There were six cases of arrhythmia in the hypothermic ischemia-reperfusion group during reperfusion.Rebeating time and duration of arrhythmias were(25.38+12.02)and(158.67±67.68)seconds,respectively.(2)The conduction sochronal diagrams at T1,T2,and T3 in the control group were uniform and regular in direction,and the conduction velocity at T2 and T3 was not different from that at T1(P＞0.05).The conduction isochronal diagrams at T2 and T3 in the hypothermic ischemia-reperfusion group were uneven and irregular in direction,and the conduction velocity was slower than that at T1(P＜0.01).The conduction velocity at T2 and T3 in the hypothermic ischemia-reperfusion group was slower than that in the control group(P＜0.01).Conduction dispersion was greater in the hypothermic ischemia-reperfusion group than that in the control group at T2 and T3(P＜0.05).(3)Compared with the control group,the protein expressions of membrane-type matrix metalloproteinase 2 and matrix metalloproteinase 2 in the hypothermic ischemia-reperfusion group were increased(P＜0.05 or P＜0.01),and the protein expression levels of type Ⅳ collagen,connexin 43 and its Ser368 phosphorylation were decreased(P＜0.05 or P＜0.01).(4)The results indicate that after hypothermic ischemia-reperfusion,myocardial extracellular matrix remodeling may mediate the downregulation of myocardial connexin 43 and its Ser368 phosphorylation,slowed conduction velocity and increased conduction dispersion,thereby increasing the risk of arrhythmia.