ObjectiveTo investigate the mechanism of Guizhi Fulingwan （GFW） against hepatic fibrosis， focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA （mtDNA）/NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsForty-two male Sprague-Dawley （SD） rats were randomly allocated into six groups （n=7）： control， model， low/medium/high-dose （0.14， 0.28， 0.56 g·kg^-1·d^-1） GFW （GFW-L， GFW-M， GFW-H）， and Dahuang Zhechong pills （DZW， 1.8 g·kg^-1·d^-1）. The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin （HE） staining and Masson's trichrome staining. Transmission electron microscopy （TEM） was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential （MMP， ΔΨ_m） was detected by flow cytometry. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction （Real-time PCR）. The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group， the model group exhibited a decrease in body weight （P<0.01）， an increase in liver index （P<0.01）， elevations in serum ALT and AST levels （P<0.01）， and typical fibrotic features such as disorganized hepatocytes， inflammatory infiltration， and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration， mitochondrial swelling， endoplasmic reticulum expansion， and organelle efflux in the model group. In addition， the model group showed decreased ΔΨ_m （P<0.01）， up-regulated mRNA levels of mtDNA and NLRP3 （P<0.01） and protein levels of NLRP3， Caspase-1， and GSDMD （P<0.01） in the liver tissue， and increased serum levels of IL-1β and IL-18 （P<0.01）. Compared with that in the model group， the body weight increased in GFW-L， GFW-M， and DZW groups （P<0.05） and markedly increased in the GFW-H group （P<0.01）. The liver index decreased in the GFW groups and DZW group （P<0.01）. The serum ALT level declined in the GFW-L group （P<0.05）， and the serum ALT and AST levels decreased in the GFW-M， GFW-H， and DZW groups （P<0.01）. Histopathological damage and fibrosis were alleviated to varying degrees， and TEM revealed mitigated ultrastructural injuries including mitophagy， mitochondrial swelling， and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨ_m increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. The mRNA level of NLRP3 was down-regulated in GFW-M， GFW-H， and DZW groups （P<0.01）. Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group （P<0.01）. The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups （P<0.01）. The protein level of cleaved Caspase-1 was down-regulated in GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. In addition， the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups （P<0.01）. ConclusionGFW can suppress pyroptosis to ameliorate CCl₄-induced hepatic fibrosis， potentially through mitigating mitochondrial damage， inhibiting inflammasome assembly and activation， and blocking pro-inflammatory cytokine release.

Objective: To explore the experience of self growth among caregivers of adolescents with non suicidal self injury (NSSI), so as to provide practical reference for improving the family support system of adolescents with NSSI. Methods: From August to November 2023, a purposive sampling method was used to select 21 caregivers of adolescents with NSSI who were treated in a tertiary grade A psychiatric hospital in Xinxiang City, Henan Province for semi structured in depth interviews. The Colaizzi s seven step qualitative analysis method was applied to analyze the data and extract themes related to caregiver growth Results: A total of 5 themes and 12 sub themes of benefit finding were extracted from caregivers of adolescents with NSSI: personal growth (increased psychological resilience, enhanced awareness of independent learning, improved self reflection ability, better understanding and acceptance of NSSI behaviors in adolescents), improvement of family relationships (improved parent-child relationship, improved relationships among family members), perceived social support (more peer support, support from close friends), improvement of caregiving ability (creating a favorable rehabilitation environment, improved caregiving skills), and changes in life and education attitudes (adopting a healthier lifestyle, reasonably adjusting expectations for children). Conclusions During the process of caring for adolescents with NSSI, caregivers from positive experiences in multiple aspects such as personal growth, family relationships, social support, and life education attitudes. Improving the mental health level of caregivers and optimize the family rehabilitation environment, will help reduce the occurrence of NSSI behaviors among adolescents.

Objective To heterologously express and purify the small ubiquitin-like modifier(SUMO)tag fused organo-phosphorus hydrolase mutant H257Y/L303T(YT),namely SUMO-YT,and evaluate its hydrolytic capacity against ethyl paraoxon and soman.Methods The SUMO tag encoding gene was constructed at the N-terminus of the YT encoding gene with a linker sequence via enzyme digestion and ligation before SUMO-YT was expressed in Escherichia coli.SUMO-YT and YT were purified through ammonium sulfate precipitation and affinity chromatography to obtain high-purity target proteins.The activity and kinetic parameters of the recombinant enzymes were examined using ethyl paraoxon and soman as substrates.Results The system for expression and purification of recombinant enzymes was established,yielding SUMO-YT and YT,and the former exhibited more significantly enhanced hydrolytic efficiency than the latter,with catalytic rates 11-fold higher for paraoxon and 4.4-fold higher for soman.At 37 ℃ and pH 7.2,SUMO-YT reduced the inhibition rate of acetylcholinesterase(AChE)by soman from 100％to 45.7％within 3 minutes,whereas YT reduced it to no more than 80％.Conclusion The high-activity recombinant SUMO-YT is prepared.SUMO tag fusion can significantly enhance the hydrolytic capacity of YT against ethyl paraoxon and soman.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

Objective To calculate the nonlinear features of motion in patients with chronic vestibular syndrome(CVS)using the largest Lyapunov exponent(LLE),and to verify the classification model's validity through machine learning algorithms.Methods A three-dimensional(3D)motion capture system was used to capture the joint motion trajectories of the subjects,which were determined using the LLE.The features of the chaotic trajectories were calculated as the input,and seven classifiers,namely the ID3 decision tree,Adaboost,C45 decision tree,Bayesian classification,Naive Bayes,and support vector machine,were used for classification.Results A total of 17 sets of trajectories from 16 joints were in the chaotic state,and the average energy,enhanced wavelength,and kurtosis of the motion trajectories in the experimental group showed significant differences(P<0.05).The ID3 decision tree classifier showed optimal performance with 100%prediction accuracy,recall,and F1-score.Conclusions Chaotic features may contain high personality differences in patients with CVS and can improve the accuracy of machine learning algorithms for recognition.These findings provide a reference for early identification and motor rehabilitation of patients with CVS.

Objective:To analyze the association of pre-pregnancy body mass index (BMI) and gestational weight gain with macrosomia.Methods:In this retrospective cohort study, data of all puerperae and newborns in the Obstetrics Center of Peking Union Medical College Hospital from July 2020 to June 2021 were collected, including basic maternal information, pregnancy complications and neonatal conditions. A total of 2 422 pregnant women with full-term singleton live birth and their newborns were included in the analysis. The incidence of macrosomia (≥4 000 g) was calculated according to the birth weight of the newborns. Logistic regression and heat map were used to analyze the associations of pre-pregnancy BMI and gestational weight gain with macrosomia.Results:The incidence of macrosomia was 4.00% (97/2 422) in full-term singleton live birth newborns. Pre-pregnancy body weight, pre-pregnancy BMI, pre-pregnancy overweight/obesity rate, pre-delivery body weight, total weight gain during pregnancy, mean weekly weight gain during pregnancy, the proportion of excessive weight gain during pregnancy, duration of pregnancy, and the proportion of primiparity and education level of junior college or below were all significantly higher in the puerperae of the macrosomia group than those in the non-macrosomia group [(63.87±8.27) vs (58.14±7.86) kg, (23.33±2.97) vs (21.60±2.72) kg/m2, 35.1% vs 17.3%, (77.48±9.11) vs (70.02±8.79) kg, (13.61±4.56) vs (11.88±4.40) kg, (0.34±0.11) vs (0.30±0.11) kg, 58.8% vs 31.1%, (280.47±7.79) vs (276.14±7.83) d, 34.1% vs 23.7%, 18.6% vs 7.5%] (all P<0.05). Pre-pregnancy BMI ( OR=1.227, 95% CI: 1.145-1.314), mean weekly weight gain during the whole pregnancy ( OR=33.453, 95% CI: 5.172-217.947), duration of pregnancy ( OR=1.083, 95% CI: 1.055-1.112), primiparity ( OR=1.969, 95% CI: 1.232-3.101) and education level of junior college or below ( OR=2.525, 95% CI: 1.325-4.668) were all positively associated with occurrence of macrosomia (all P<0.05). The incidence of macrosomia increased with the pre-pregnancy body mass index and mean weekly weight gain during the whole pregnancy. Conclusions:High pre-pregnancy BMI and mean weekly weight gain during the whole pregnancy are associated with the increased risk of macrosomia. Appropriate weight management during pregnancy may help to reduce the incidence of adverse pregnancy outcomes.

Background: We systematically searched and summarized clinical studies on traditional Chinese medicine (TCM) for age-related macular degeneration (AMD) with the method of evidence map. We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future. Materials and methods: We searched PubMed, Web of Science, EMBASE, and Chinese databases including CNKI (Chinese National Knowledge Infrastructure), WanFang and VIP, ClinicalTrials.gov, and Chinese Clinical Trial Registry Center studies on the prevention or treatment of TCM for AMD from January 2000 to November 2022. We showed distribution features of these studies in the form of text description, graphs, and tables. Results: The final 258 articles included 245 clinical studies, 9 systematic reviews or meta-analyses, and 4 guidelines, expert consensus, or clinical pathway. After analyzing the articles with a focus on the stage of AMD, study type, sample size, intervention measures, outcome indicators, and the quality of evidence, we found that the studies were increasing, most of which were wet AMD, the main study type was randomized controlled trials, and the sample size was mostly fewer than 100 cases. Different interventions of TCM, such as Chinese medicine, Chinese patent medicine, or acupuncture, showed the potential benefits of improving vision, reducing fundus lesions, and alleviating some uncomfortable symptoms. However, the sample size of these studies was small. The outcome indicators were not unified, and the stage of AMD was unclear. The quality of articles was lower, and there were few studies on early AMD. The advantages of TCM for the prevention or treatment of AMD remained unclear. Conclusions: Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM, and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.