BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Objective To analyze the adverse reaction reports （ADRs） of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use. Methods ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on. Results In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury （37.84%）. The age of drug-induced liver injury was mainly over 46 years, totaling 195 （75.28%）. Drugs were mainly distributed in cardiovascular system medicine （44.02%）, anti-infective medicine （23.94%）and anti-tumor medicine （11.58%）. Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases （46.49%）. The main anti-infectious drugs were cephalosporins （29.03%）, carbapenem （19.35%）， antifungal （17.74%）and quinolones （11.29%）. Adverse reactions occurred within 6 days （69.88%）, the duration of adverse reactions was 1-2 weeks （31.66%）, and most patients were improved （47.88%） or cured （37.07%）. Conclusion For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Objective:To explore the effects of smoking on peripheral regulatory T cells (Tregs), transforming growth factor beta1 (TGF-β 1) and interleukin-10 (IL-10) in elderly patients with non-small cell lung cancer (NSCLC). Methods:This was a cross-sectional study. A total of 43 elderly patients (≥60 years old) who were hospitalized in the Department of Geriatrics Medicine, Guangzhou First People′s Hospital from January 2018 to December 2024 and were newly diagnosed with NSCLC were recruited. According to smoking history, patients were divided into non-smoking group (15 cases), low smoking group (13 cases, smoking index<400) and high smoking group (15 cases, smoking index≥400). Venous blood samples were collected from participants, plasma and cells were separated. Flow cytometry was used to measure the proportions of Tregs and the expression of forkhead box P3 (Foxp3) in peripheral blood. Plasma levels of TGF-β 1 and IL-10 were measured by enzyme-linked immunosorbent assay. The effects of smoking on peripheral Tregs, TGF-β 1, and IL-10 in elderly patients with NSCLC were analyzed. Data were analyzed by one-way ANOVA, rank-sum test, and Fisher′s exact test. Results:The proportions of Tregs in non-smoking group, low smoking group and high smoking group were 2.50% (2.32%, 2.81%), 2.83% (2.48%, 3.72%), and 3.01% (2.37%, 3.73%), respectively, and there were no statistically significant differences among the three groups ( H=3.845, P>0.05). The proportions of Foxp3 +Tregs were (3.72±0.84)%, (4.64±1.10)%, and (4.68±1.27%), respectively. The mean fluorescence intensities (MFI) of Foxp3 were 123.0 (108.0, 128.0), 131.0 (123.5, 350.0), and 222.0 (141.0, 311.0), respectively. Both the proportions of Foxp3 +Tregs and the MFI of Foxp3 were higher in low smoking group and high smoking group than those in non-smoking group (all P<0.05). However, there were no significant differences between low smoking group and high smoking group (all P>0.05). The concentrations of IL-10 were 2.27 (1.42, 3.95), 3.42 (2.30, 5.08), and 3.26 (2.35, 6.28) ng/L, respectively. There were no statistically significant differences among the three groups ( H=2.930, P>0.05). The concentrations of TGF-β 1 were (10.72±9.37), (13.46±10.39), and (25.28±16.67) ng/ml, respectively. The concentration of TGF-β 1 in high smoking group was higher than that in non-smoking group and low smoking group (all P<0.05). However, there was no statistically significant difference between low smoking group and non-smoking group ( P>0.05). Conclusions:Smoking intensity may be correlated with the immunosuppressive function of Tregs in elderly patients with NSCLC. Higher smoking levels are associated with increased Foxp3 expression in Tregs and elevated plasma levels of TGF-β 1, potentially enhancing the immunosuppressive function of Tregs.

Objective:To assess the association between temperature and risk of animal injury, and identifying vulnerable populations.Methods:Based on a time-stratified case-crossover design, the number of animal injuries monitored in hospitals of Guangdong Provincial Injury Surveillance System in 2011 and 2015-2016 was included, and the daily meteorological data were derived from the fifth generation of European ReAnalysis-Land, which was produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression combined with a distributed lagged nonlinear model was applied to analyze the association of temperature and animal-specific injuries. We also conducted stratified analysis by region, sex, age, occupation, and location of injury occurrence.Results:There was an almost linear relationship between temperature and the occurrence of animal injury. The excess risk ( ER) of animal injury was 2.65% (95% CI: 2.27%-3.04%) for a 1 ℃ rise in temperature with much higher risk of occurrence ( ER=9.34%, 95% CI: 7.57%-11.13%) for non-mammalian injury than that for mammalian injuries ( ER=2.30%, 95% CI: 1.90%-2.70%). Stratified analysis revealed that the occurrence of animal injury was more susceptible to temperature influences in urban ( ER=2.78%, 95% CI: 2.35%-3.21%), female ( ER=2.71%, 95% CI: 2.16%-3.27%), the elderly aged 60 years and above ( ER=3.05%, 95% CI: 1.65%- 4.47%), farmer ( ER=4.66%, 95% CI: 3.03%-6.32%) and agricultural area ( ER=10.63%, 95% CI: 7.57%-13.79%) than their correspondents. In terms of mammalian injury, dog bites showed the highest risk ( ER=2.71%, 95% CI: 2.12%-3.30%). In terms of non-mammalian,snake injuries were highly influenced by temperature ( ER=16.74%, 95% CI: 11.33%-22.40%). Conclusions:The ambient temperature rises could increase the risk of animal injury with much higher risk for non-mammalian than that for mammalian injuries. Our findings suggest that global warming may increase the risk and disease burden from animal injuries.

Objective To explore the role in sleep staging from blood volume pulse(BVP)and triaxial acceleration(ACC)of body movement obtained by wristband.Methods The BVP and ACC obtained by Empatica E4 wristband were used from all 100 cases of sleep disorder subjects in the DREAMT public database.Two frequency domain characteristics(eS,LF/HF)and one time domain characteristic(vA)of the BVP baseline and the activity counts(CS)of the ACC were used for sleep-awakening classification based on random forest.Results The results of sleep-awakening classification of all 100 cases of sleep disorder subjects were obtained by leaving-one-out strategy.The accuracy is 79.8%and the Kappa coefficient is 0.56 by 4 features from BVP and ACC;the accuracy is 70.4%and the Kappa coefficient is 0.36 by 3 features of BVP;the accuracy is 75.1%and the Kappa coefficient is 0.47 based on activity counts.Conclusion The BVP and ACC obtained by the wristband can be used for the rough estimation of sleep and awakening for sleep disorder subjects,among which the importance of ACC is higher than that of BVP.