Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Purpose: To evaluate the effectiveness of advanced practice nurse–guided home-based rehabilitation exercise program (HREPro) among patients with lower limb spasticity post-stroke. Methods: This randomized controlled study recruited 121 patients with lower limb spasticity post-stroke. Intervention (n = 59) and control (n = 62) groups underwent 12-month HREPro and conventional rehabilitation, respectively, after discharge. The Fugl–Meyer assessment of spasticity measurement, modified Ashworth scale of motor function, 10-Meter Walk Test of walking ability, and Barthel index of activities of daily living (ADL) were evaluated at 0, 3, 6, and 12 months after discharge. Results: Significant differences were found in spasticity degree, motor function, walking ability, and ADL at 6 and 12 months after discharge between the control and intervention groups. Lower limb spasticity and ADL in the intervention group were significantly improved. Conclusion HREPro is effective for rehabilitation of patients with lower limb spasticity post-stroke and has favorable home application.

Purpose: To evaluate the effectiveness of advanced practice nurse–guided home-based rehabilitation exercise program (HREPro) among patients with lower limb spasticity post-stroke. Methods: This randomized controlled study recruited 121 patients with lower limb spasticity post-stroke. Intervention (n = 59) and control (n = 62) groups underwent 12-month HREPro and conventional rehabilitation, respectively, after discharge. The Fugl–Meyer assessment of spasticity measurement, modified Ashworth scale of motor function, 10-Meter Walk Test of walking ability, and Barthel index of activities of daily living (ADL) were evaluated at 0, 3, 6, and 12 months after discharge. Results: Significant differences were found in spasticity degree, motor function, walking ability, and ADL at 6 and 12 months after discharge between the control and intervention groups. Lower limb spasticity and ADL in the intervention group were significantly improved. Conclusion HREPro is effective for rehabilitation of patients with lower limb spasticity post-stroke and has favorable home application.

OBJECTIVE: To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins. METHODS: In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (β value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively. RESULTS: In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (P_FPG=2.42×10^-19, FDR_FPG<0.001; P_HbA1c=1.72×10^-19, FDR_HbA1c<0.001). CONCLUSION In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.
Adult ; Blood Glucose ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Fasting ; Female ; Glycated Hemoglobin A ; Humans ; Male ; Middle Aged ; Twins, Monozygotic

Objective To study the pollution and source apportionment differences of different periods PM2.5 in the residential community of suburb in Tianjin City during heating and non-heating periods. Methods From 2015 to 2016, daytime and nighttime PM2.5 samples were collected at a community in the suburb of Tianjin. The mass concentration of PM2.5 samples and major chemical components in PM2.5, including metal elements, polycyclic aromatic hydrocarbons (PAHs) and inorganic water-soluble ions were monitored. Positive matrix factorization (PMF) model was used to apportion potential sources of metal elements, PAHs and inorganic water-soluble ions in daytime and nighttime PM2.5. Results In the heating period, the concentrations of some metal elements of suburban residential community were higher in the daytime than in the nighttime. In the non-heating period, the concentrations of some PAHs and inorganic water-soluble ions of suburban residential community were higher in the nighttime than in the daytime. Meanwhile, the concentrations of some metal elements were greater in the daytime than in the nighttime. When in heating period, the main source of PM2.5 in the suburban residential community was coal combustion during daytime and its source contribution rate was 50.1% while secondary aerosol and fuel combustion emissions of gasoline and diesel vehicles were main sources during nighttime and their source contribution rates were 41.0% and 35.9%. The principal source of daytime PM2.5 in the suburban residential community was indoor activity emissions during non-heating period, and secondary aerosol was main source during nighttime and their source contribution rates were 29.8% and 31.1%. Conclusions The pollution status of PM2.5 in residential communities of suburban is serious, and the source apportionment of day and night PM2.5 samples has different in different heating periods.

Through indoor and field comparative experiments, the properties of membrane type leaf evaporation inhibitors and its effects on photosynthesis of and compatibility and synergistic of pesticide were studied. The evaporation inhibitors and were chosen to investigate the suppression of water evaporation and the compatibility with pesticides. The effect of evaporation inhibitors on photosynthesis of leaves was determined by the chlorophyll fluorescence imaging system. The results showed that water evaporation of leaves of different leaf age were evidently suppressed after treated with evaporation inhibitor. The inhibitor was well compatible with pesticide and effectively improved the pesticide efficacy，and had no significant effect on chlorophyll fluorescence parameters. It is concluded that the evaporation inhibitor has good compatibility with the pesticide, and has remarkable effect of restraining moisture evaporation, which make it can be used for reducing the dosage and improving the efficacy of the pesticide in the field of
Chlorophyll ; analysis ; Lycium ; drug effects ; physiology ; Pesticides ; chemistry ; Photosynthesis ; Plant Leaves ; drug effects ; physiology ; Plant Transpiration

This paper reviewed international documents of disability statistics. The results showed that all disability measurements had been adopted International Classification of Functioning, Disability and Health (ICF) terminology and approach. Disability statistics in US tailored to ICF framework and classification. Disability statistics in China had partially adopted ICF approach.

OBJECTIVE: To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population. METHODS: A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05. RESULTS: After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways. CONCLUSION There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.
Adult ; Blood Pressure ; Body Weight ; CpG Islands ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Twins, Monozygotic

BACKGROUND:Our preliminary findings have shown that stem cells have a certain effect on early formation of renal fibrosis and delay the occurrence of renal interstitial fibrosis.OBJECTIVE:To investigate the effect of exogenous adipose-derived stem cell transplantation on the formation of renal interstitial fibrosis in rats,and to explore the dose-effect relationship.METHODS:Fifty Sprague-Dawley rats were randomly divided into five groups.Rats in sham operation group were injected with PBS;and those in the other four groups were ligated to establish the model of renal fibrosis.After successful modeling,the model group was injected with PBS,while low dose group,middle dose group and high dose group were injected with 1 ×107/L,2x107/L,3x107/L adipose-derived stem cell suspension (0.1 mL),respectively.Rats were killed 14 days after injection.Hematoxylin-eosin staining and Masson staining were used to observe the degree of renal tubular interstitial injury and the relative area of the renal interstitium.Expression of alpha smooth muscle actin and transforming growth factor beta1 was detected by immunohistochemistry.RESULTS AND CONCLUSION:(1) Hematoxylin eosin staining:The model group showed typical glomerular and tubulointerstitial changes;the low,middle and high dose groups had a certain degree of glomerular and tubulointerstitial changes,but the severity of injury in these three groups,especially in the high dose group,was significantly milder than that in the model group.(2) Masson staining:In the model group,the renal interstitium was widened and the collagen fibers were deposited;in the low,middle and high dose groups,the degree of renal interstitial expansion was lower than that in the model group,and moreover,the degree of renal interstitial expansion in the middle and high dose groups was lower than that in the low dose group (P ＜ 0.05).(3) Immunohistochemical staining:Compared with the sham operation group,the expression of alpha smooth muscle actin and transforming growth factor beta1 in the model group was higher than that in the sham operation group (P ＜ 0.05).Compared with the model group,significantly decreased expression of alphasmooth muscle actin was found in the high dose group (P ＜ 0.05) and significantly reduced transforming growth factor beta1 expression was observed in the high,middle,and low dose groups (P ＜ 0.05),especially in the middle and high dose groups.To conclude,exogenous adipose-derived stem cell transplantation can delay the formation of early renal fibrosis in a dose-effect manner,which may be realized by changing the signal pathway state induced by transforming growth factor beta1.

To evaluate the neuroprotective effect of nerve growth factor ( NGF ) on acute angle-closure glaucoma patients after trabeculetomy.METHODS: Patients with viral keratitis who underwent trabeculectomy in treatment of acute angle - closure glaucoma in Xiamen Eye Center of Xiamen University from December 2011 to October 2013 were selected and completed the treatment, 61 eyes of 45 cases were followed up. The treatment group of 23 cases (32 eyes) with acute angle-closure glaucoma patients were treated by NGF gel for 3mo after trabeculetomy, while in the control group 22 cases (29 eyes) were treated by normal saline replaced NGF. All patients were followed up for at least 12mo, visual acuity, perimetry, retinal nerve fiber layer ( RNFL) thickness and cup/disc ratio of the patients were followed up during the treatment. The safety of topical use of NGF gel was also evaluated.RESULTS:ln all patients, the intraocular pressure ( lOP) was successfully controlled under 21mmHg and the visual acuity was markedly increased in the affected eye after trabeculectomy. Compared with control group, the postoperative lOP and visual acuity had no significant differences in treatment group (P>0. 05). The average light sensitivity of perimetry and mean defect were better than that in control group postoperative 6 and 12mo; The results of optical coherent tomography ( OCT ) and Heiderburg Retina Tomography ( HRT )-Ⅲ showed that RNFL thickness was significantly greater than that in control group, while cup/disc ratio significantly less than that in control group postoperative 6 and 12mo. Ocular surface damage, corneal endothelium to reduce and other eye complication were no observed in treatment group.CONCLUSlON:Acute angle-closure glaucoma treated by NGF gel after operation is effective and safe.