Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

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 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.

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.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

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.

Organ transplantation is an effective treatment for end-stage organ failure, but postoperative infections and rejection reactions are key factors affecting the survival of the patients. Recently, the incidence of human parvovirus B19 (B19V) infection following transplantation has increased. B19V is a non-enveloped virus that primarily infects the upper respiratory tract and exhibits significant tropism for erythroid progenitor cells in the bone marrow, leading to the lysis of erythrocytes and hematological abnormalities. After B19V viremia, it may further infect other cells, triggering inflammatory responses and tissue damage. B19V infection may lead to chronic anemia in organ transplant patients, thereby affecting the success of the transplant and the survival of the patients. Therefore, it is essential to diagnose and monitor B19V infection post-transplantation. Due to the immunosuppressive therapy following transplantation, traditional serological detection methods, such as IgM and IgG antibody tests, are often unreliable. In contrast, molecular biological detection, especially real-time fluorescent quantitative PCR technology, provides more accurate results. However, the diversity of B19V genotypes may lead to the missed detection of some genotypes. Thus, it is necessary to use different detection techniques to improve the diagnostic accuracy of B19 virus infections. Additionally, there is a need to explore more precise diagnostic methods to enhance the early identification and management of B19V infection, further improving the survival and life quality of the patients.

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