Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Objective:To explore the current status of nutrition impact symptoms in patients with liver cirrhosis and to explore its influencing factors.Methods:Convenience sampling was used to select liver cirrhosis inpatients from three ClassⅢ Grade A hospitals in Fuyang City, Anhui Province, from November 2022 to November 2023 for the study. General Information Questionnaire, Eating Symptoms Questionnaire (ESQ), Perceived Social Support Scale (PSSS), and Simplified Coping Style Questionnaire (SCSQ) were used to investigate the participants. Binary Logistic regression was used to explore the factors that influence nutrition-impact symptoms in liver cirrhotic patients.Results:A total of 394 questionnaires were distributed, and 384 valid questionnaires were recovered, with an effective recovery rate of 97.5%. Of the 384 patients with liver cirrhosis, 274 patients (71.4%) had at least one nutrition impact symptom, and 166 patients (43.2%) had at least one moderate-to-severe nutrition impact symptom. Patients' most common nutrition impact symptoms include dry mouth, altered taste, and bloating. Binary Logistic regression analysis showed that age, liver cirrhosis stage, total bilirubin, coping styles, and social support were the influencing factors of nutrition impact symptoms in patients with liver cirrhosis, and the differences were statistically significant (all P<0.05) . Conclusions:The detection rate of nutrition impact symptoms in patients with liver cirrhosis is high. Healthcare professionals can alleviate moderate-to-severe nutrition impact symptoms by guiding patients to adopt positive coping styles and helping to improve social support.

Objective:To explore the feasibility of modifying hemerythrin molecules with natural cross-linker genipin,and evaluate its efficacy and safety.Methods:Hemerythrin was isolated and purified from sipunculid worms using tangential flow ultrafiltration.Subsequently,genipin cross-linked hemerythrin nanoparticles(GHrNPs)were constructed by adding 20％w/w genipin under mildly acidic conditions,and glutaraldehyde cross-linked hemerythrin nanoparticles(GAHrNPs)were constructed by adding 10％w/w glutaraldehyde under mildly alkaline conditions.The diameter,dispersity index,zeta potential,functional group structure,P50,and Hill coefficient of the two nanoparticle groups were measured.The two nanoparticle groups at different concentrations were co-cultured with vascular endothelial cells for 24 hours,then the cell viability and NO concentration in the culture medium were measured.Results:After glutaraldehyde/genipin molecular cross-linking,infrared spectra showed the continuous presence of amide bands Ⅰ and Ⅱ.The hydrated particle sizes of hemerythrin,GHrNP and GAHrNP were(93.14±2.11),(109.53±3.54),and(115.65±2.65)nm,dispersity indexes were 0.30±0.06,0.27±0.05,and 0.25±0.03,zeta potentials were(-24.00±1.54),(-19.52±1.31),and(-18.90±1.25)mV,P50 values were(9.28±0.22),(8.50±0.54),and(5.75±0.90)mmHg,and Hill coefficients were 1.61±0.14,1.58±0.17,and 1.41±0.22,respectively.The average hydrated particle size increased after cross-linking with hemerythrin,the negative value of the zeta potential decreased(both P＜0.05).The P50 value of GAHrNP was significantly decreased than that of hemerythrin and GHrNP(P＜0.05).The viability of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group at different mass concentrations(P＜0.05).The NO concentration in the culture medium of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group only at 2.0 mg/ml(P＜0.05).Conclusion:Hemerythrin molecules cross-linked by genipin can form stable nanoparticles with good oxygen-carrying activity and lower cytotoxicity compared to glutaraldehyde.

Objective:To explore the feasibility of modifying hemerythrin molecules with natural cross-linker genipin,and evaluate its efficacy and safety.Methods:Hemerythrin was isolated and purified from sipunculid worms using tangential flow ultrafiltration.Subsequently,genipin cross-linked hemerythrin nanoparticles(GHrNPs)were constructed by adding 20％w/w genipin under mildly acidic conditions,and glutaraldehyde cross-linked hemerythrin nanoparticles(GAHrNPs)were constructed by adding 10％w/w glutaraldehyde under mildly alkaline conditions.The diameter,dispersity index,zeta potential,functional group structure,P50,and Hill coefficient of the two nanoparticle groups were measured.The two nanoparticle groups at different concentrations were co-cultured with vascular endothelial cells for 24 hours,then the cell viability and NO concentration in the culture medium were measured.Results:After glutaraldehyde/genipin molecular cross-linking,infrared spectra showed the continuous presence of amide bands Ⅰ and Ⅱ.The hydrated particle sizes of hemerythrin,GHrNP and GAHrNP were(93.14±2.11),(109.53±3.54),and(115.65±2.65)nm,dispersity indexes were 0.30±0.06,0.27±0.05,and 0.25±0.03,zeta potentials were(-24.00±1.54),(-19.52±1.31),and(-18.90±1.25)mV,P50 values were(9.28±0.22),(8.50±0.54),and(5.75±0.90)mmHg,and Hill coefficients were 1.61±0.14,1.58±0.17,and 1.41±0.22,respectively.The average hydrated particle size increased after cross-linking with hemerythrin,the negative value of the zeta potential decreased(both P＜0.05).The P50 value of GAHrNP was significantly decreased than that of hemerythrin and GHrNP(P＜0.05).The viability of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group at different mass concentrations(P＜0.05).The NO concentration in the culture medium of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group only at 2.0 mg/ml(P＜0.05).Conclusion:Hemerythrin molecules cross-linked by genipin can form stable nanoparticles with good oxygen-carrying activity and lower cytotoxicity compared to glutaraldehyde.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/analysis* ; Software ; Medicine, Chinese Traditional ; Quality Control

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*