Scar formation is characterized by dynamic alterations in collagen secretion, which critically determine scar morphology and pathological progression. In fibroblasts, collagen secretion is initiated through the activation of cytokine- and integrin-mediated signaling pathways, which promote collagen gene transcription. The procollagen polypeptide α chains undergo extensive post-translational modifications, including hydroxylation and glycosylation, within the endoplasmic reticulum (ER), followed by folding and assembly into triple-helical procollagen. Subsequent intracellular trafficking involves the sequential transport of procollagen through the ER, Golgi apparatus, and plasma membrane, accompanied by further structural refinements prior to extracellular secretion. Once secreted, procollagen is enzymatically processed to form mature collagen fibrils, which drive scar tissue remodeling. Recent advances in elucidating regulation of collagen secretion have identified pivotal molecular targets, such as transforming growth factor-beta 1 (TGF-β1), prolyl 4-hydroxylase (P4H), heat shock protein 47 (HSP47), and transport and Golgi organization protein 1 (TANGO1), providing novel therapeutic strategies to mitigate pathological scar hyperplasia and improve regenerative outcomes. This review provides a comprehensive analysis of the molecular mechanisms governing collagen secretion during scar formation, with emphasis on signaling cascades, procollagen biosynthesis, intracellular transport dynamics, and post-translational modifications, thereby offering a framework for developing targeted anti-scar therapies.
Humans ; Collagen/metabolism* ; Cicatrix/pathology* ; Signal Transduction ; Transforming Growth Factor beta1/metabolism* ; Fibroblasts/metabolism* ; Animals

Objective To investigate the transition intensity and transition probabilities of fall states among middle-aged and older adults in China,and to assess the impact of potential risk factors on falls.Methods We utilized in the study data from the China Health and Retirement Longitudinal Study(CHARLS)and employed a multi-state Markov model(MSM)to analyze the transition intensity and probabilities between states of no falls or falls without treatment,falls requiring treatment,and death.Results A total of 14722 participants were enrolled,with a mean age of(59.4 years±9.7 years),and 47.9％were male.The median follow-up period was 9 years(interquartile range[IQR].7-9 years).At baseline,12381 participants(84.1％)reported no falls or falls without treatment,while 2341(15.9％)reported falls requiring treatment.Participants who experienced falls requiring treatment within one follow-up cycle had a 55.2％probability of not falling again or only falling without treatment in the subsequent two years,a 37.6％probability of continuing to experience falls requiring treatment,and a 7.2％probability of death.The risk of transitioning from a state of no falls or falls without treatment to falls requiring treatment increased by 8.6％for every 5-year increase in age.The risk was 35.1％higher for females compared to males.Rural residents had a 10.1％higher risk.Those who were divorced,separated,widowed,or never married had a 20.7％higher risk.Higher degrees of physical function impairment were associated with an increased risk.Depressive symptoms increased the risk by 31.6％.Having one chronic disease raised the risk by 9.6％,while multimorbidity led to a 28.8％increase in risk.Conclusion According to the findings of the study,falls are a dynamic process and emphasis should be given to fall prevention for older adults,individuals with a history of fall-related medical visits,those living alone,those with impaired physical function,and those with depressive symptoms.

Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9).Methods::From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005-1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168-2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions::RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9).Methods::From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005-1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168-2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions::RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Objective To investigate the correlation between iron metabolism index and intelligence development of Dongxiang and Han students in Dongxiang county and Lanzhou city of Gansu province.Methods A total of 396 students aged from 6 to 11 years old were randomly selected for venous blood collection from two primary schools with Dongxiang and Han children in Dongxiang county and Lanzhou city.Blood routine and serum iron metabolism indicators were detected and iron metabolism indicators from different ethnic groups were analyzed.Students diagnosed with iron deficiency anemia(IDA) named as IDA group,and students without IDA who had similar background were enrolled in the control group.The correlation between iron metabolism index and intelligence quotient was analyzed.Results The ferritin level of Dongxiang students (51.81 μg/L)was lower than that of Han students(65.73 μg/L),and total iron binding capacity of students in Dongxiang county [(65.04 ± 6.68) μ mol/L] was higher than that of students in Lanzhou city [(59.92 ±5.91) μmol/L].The transferrinsaturation of students in Dongxiang county [0.23 (0.19 ～ 0.30)] was lower than that of students in Lanzhou city[0.26(0.20 ～0.32)].The differences were statistically significant(P ＜0.05).Analysis of multiple linear regression showed that ferritin and serum iron were correlated to intelligence quotient score of the IDA students (P ＜ 0.05).Conclusion Ferritin and serum iron are associated with primary school students' intelligence quotient.Religious practice,regional economic and cultural level have a certain influence on iron metabolism of local primary school students.It is very important to strengthen the supplement of dietary iron in primary school students in Dongxiang County and reduce the prevalence of iron deficiency.

Objective:To study urine albumin excretion (UAE) and its related factors in patients with essential hyper‐tension (EH) .Methods :A total of 113 EH patients without significant target organ damage were enrolled as EH group ,while another 92 healthy subjects were regarded as healthy control group .Ratio of morning urinary albumin to creatinine was measured and regarded as UAE index .Plasma homocysteine (Hcy) ,serum uric acid ,creatinine , blood urea nitrogen ,blood glucose ,blood lipids etc .levels were measured ,and compared between two groups Re‐sults:Compared with healthy control group ,there were significant rise in UAE ,body mass index (BMI) ,waist hip ratio ,blood pressure ,pulse pressure ,heart rate ,plasma levels of triglyceride (TG) ,low density lipoprotein choles‐terol (LDL‐C) ,serum uric acid and Hcy (P<0.05 or <0.01) ,and significant reduction in level of high density lip‐oprotein cholesterol (HDL‐C) in EH group ( P=0.001) .Pearson correlation analysis indicated that lgUAE was pos‐itively correlated with lgTG (r=0.257 ,P=0.015) and estimated glomerular filtration rate (eGFR ,r=0.284 ,P=0.007) ,and inversely correlated with lg creatinine (r= -0.277 ,P=0.008) in healthy control group ,while in EH group ,lgUAE was positively correlated BMI (r=0.231 ,P=0.014) ,lgTG (r=0.200 ,P=0.034) and lgHcy (r=0.244 , P=0.009) .Muti-factor gradual regression analysis indicated that lg TG (β=0.265 ,P=0.001) and lg Hcy (β=0.170 , P=0.012) were independently positively correlated with lg UAE , R2 =0.112.Conclusion:UAE level significantly rises in EH patients ,and it′s significantly positively correlated with plasma levels of TG and Hcy .

Objectives To investigate the associations of the plasma homocysteine levels with the alterations in arterial stiffness in a commu-nity-based cohort. The gender differences in these associations were examined. Methods We evaluated the relationship between plasma homocysteine levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age:61.5 years;709 men, 971 women) from communities of Beijing, China. Results In univariate analysis, plasma homocysteine levels was positively related to the CF-PWV (r=0.211, P<0.0001) and CA-PWV (r=0.148, P<0.0001), whereas inversely associated with AI (r=?0.052, P=0.016). In multiple linear regression models adjusting for covariants, plasma homocysteine remained positively related to the CF-PWV (standardizedβ=0.065, P=0.007) in total cases. When the groups of men and women were examined separately, plasma homocysteine remained positively associated with the CF-PWV (standardizedβ=0.082, P=0.023) in men, whereas the relations between homocysteine and any of the arterial stiffness indices were not further present in women. Conclusions In Chinese population, plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women.

Objective To investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers. Methods A cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects. Results In both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85 ± 6.55 mmHg) than in the hypertensives (12.64 ± 6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP. Conclusion The central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

Objective To investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers. Methods A cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects. Results In both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85 ± 6.55 mmHg) than in the hypertensives (12.64 ± 6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP. Conclusion The central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

BACKGROUNDN-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury. However, it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.

METHODSIn a community based study, levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years. The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml. The association of hs-cTnT levels and NT-proBNP levels was analyzed.

RESULTSWhen the subjects with undetectable (<0.003 ng/ml), intermediate (0.003-0.014 ng/ml), and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r = 0.175, P < 0.001), a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β = -0.206, P < 0.001; β = -0.118, P < 0.001, respectively). In multivariable analyses, older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β = 0.341, P < 0.001; β = 0.143, P < 0.001, respectively), and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels. When the subjects with normal or elevated NT-proBNP were analyzed separately, the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group, whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β = 0.399, P < 0.01).

CONCLUSIONSIn this community based population, NT-proBNP elevation was common. In addition to female gender and older age, subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.

Biomarkers ; analysis ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Troponin T ; blood