Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

BackgroundNon-suicidal self-injury （NSSI） behaviors have become a serious global public health issue.The detection rate of NSSI behaviors among college students in China ranges from 9.8% to 13.53%. Integrated theoretical models suggest that distal family risk factors influence NSSI behaviors through emotional regulation mechanisms. However， existing researches have predominantly focused on single family risks， leaving the relationship between cumulative family risks and NSSI behaviors， as well as the underlying pathways， remain unclear. ObjectiveTo explore the effects of cumulative family risk on NSSI behaviors among college students， analyze the chain mediating roles of emotional regulation difficulties and depression， and examine the moderating effect of gender， so as to provide references for targeted interventions for NSSI behaviors in college students. MethodsOn March 1， 2024， a cluster sampling method was employed to select 518 college students from two universities in Heilongjiang Province. Assessments were conducted using Chinese version of the Childhood Trauma Questionnaire （CTQ）， the Difficulties in Emotion Regulation Scale （DERS）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and the Adolescent Self-Injury Questionnaire. Logistic regression analysis was used to examine the impact of cumulative family risk factors on NSSI behaviors among college students. Model 6 in Process 4.1 was applied to test the chain mediating roles of emotional regulation difficulties and depression in the relationship between cumulative family risk and NSSI behaviors， while model 83 was utilized to analyze the moderating effects of gender on the path "cumulative family risk → emotion regulation difficulties". ResultsA total of 475 （91.70%） college students completed valid questionnaires. Logistic regression analysis revealed that childhood abuse （OR=2.561， 95% CI： 1.566-2.561）， non-parental family structure （OR=2.108， 95% CI：1.102-4.029） and left-behind experience （OR=2.356， 95% CI： 1.021-5.439） were risk factors for NSSI behaviors among college students. Cumulative family risk positively predicted NSSI behaviors （β=0.345，95% CI：1.059-4.286， P<0.01）， and this relationship was mediated by a chain pathway involving emotional regulation difficulties （β=0.136，95% CI： 0.882-4.681， P<0.05） and depression （β=0.160， 95% CI： 0.316-1.073， P<0.01）. Gender moderated the relationship between cumulative family risk and emotional regulation difficulties （β=0.103， 95% CI： 1.567-8.316， P<0.01）， with cumulative family risk significantly predicting emotional regulation difficulties in female students （β=0.374， 95% CI： 0.099-0.084， P<0.01）. ConclusionCumulative family risk can directly influence college students' NSSI behaviors， and may also indirectly affect NSSI behaviors through the mediating roles of emotional regulation difficulties and depression. The path "cumulative family risk → emotional regulation difficulties" in this mediating model is moderated by gender.［Funded by Heilongjiang Philosophy and Social Sciences Research Planning Project （number， 24SHB007）］

Objective To analyze the detection efficiency of p16INK4a protein combined with human papillomavirus and liquid-based cytology(LCT)in the screening of cervical precancerous lesions,and to provide a basis for cervical cancer preven-tion and treatment.Methods The results of p16INK4a staining of cervical epithelial cells,human papillomavirus testing and cer-vical cytology were analyzed in 139 inpatients at Guangzhou Women's and Children's Medical Center between January 2019 and December 2020.Of them,there were 111 patients with cervical intraepithelial neoplasia(CIN)and 28 cases of cervical inflam-matory disease.The efficacy of the three methods alone and in combination to screen for CIN lesions was compared.Results In the detection of CIN patients,the sensitivity of p16INK4a,microfluidic microarray and cervical cytology for detecting CIN and a-bove lesions was 91.89% ,94.59% and82.88% ,with specificity of 57.14% ,17.86% and46.43% ,and AUC of 0.75,0.56 and 0.65,respectively;while the sensitivity of"p16INK4a+LCT","p16INK4a+hrHPV","LCT+hrHPV"and their sen-sitivity were 96.40% ,97.30% ,94.59% and 99.10% ,their specificity was 85.71% ,92.86% ,89.29% and 92.86% ,and the AUC was 0.91,0.95,0.92 and 0.96,respectively.Conclusion The combined p16INK4a and hrHPV test helps to improve diagnostic accuracy and early detection,thus allowing for earlier intervention or treatment.This combined application allows for more accurate identification of low-grade and high-grade cervical intraepithelial neoplasia,providing more information for indi-vidualized patient management.

Objective To study mechanical properties of polyethylene terephthalate (PET)-based textile valves woven with nickel-titanium (NiTi) wires by finite element method, and combined with in vitro hemodynamic testing, to analyze the effect of wire quantity and woven position on hemodynamic performance of PET textile valve. Methods The three-dimensional (3D) geometric models of PET valves without wires and models of PET valves with wires by different numbers and distributions in radial direction were constructed using modeling software. Material properties of PET valves and wires were given based on the literature and experimental data. The transvalvular pressure difference curves of PET valves obtained from in vitro pulsatile flow experiments were used as boundary conditions. Stress distributions of the valve during peak systole and diastole were studied by finite element analysis software. Hydrodynamic performance of the valve with wires was evaluated by in vitro pulsatile flow experiments. ResultsThe finite element analysis results showed that the radially woven NiTi wires could enhance support for the PET textile valve, and support force and area of the valve in belly region of the valve leaflet with evenly distributed metal wires increased with the number of metal wires. The situation of support force was similar for silk distributions on both sides of the belly. The weaving of wires reduced stress concentration on the PET textile valve to a certain extent. The pulsatile flow experiment results showed that the stability of opening and closing shapes, effective opening area (EOA), regurgitation fraction (RF) and transvalvular pressure differences for two kinds of the PET valves with woven wires were better than those of the PET valves without wires. Conclusions Weaving metal wires in radial direction of the PET textile valve can effectively reduce stress concentrations on the PET textile valve during the cardiac cycle, and reduce tearing possibility of the valve leaflet. The woven metal wires can improve opening and closing stability of PET textile valve in in vitro hydrodynamic test, increase EOA and reduce RF and transvalvular pressure difference of the PET valve.

OBJECTIVE: To understand the current status and influencing factors of job burnout in rural preschool teachers. METHODS: A stratified cluster random sampling method was used to investigate the job burnout and social support of 756 rural preschool teachers in Sichuan Province using the Maslach Burnout Inventory, Educators Survey and Social Support Revalued Scale. RESULTS: The positive rate of job burnout was 22.1%(167/756), and the positive rates of emotional exhaustion, reduced personal achievement, and depersonalization were 13.1%, 10.7% and 1.2%, respectively. The results of unconditional logistic regression analysis showed that post status, daily working hours, subjective support and utilization of support were all related to job burnout(P<0.05). Among them, in-post and daily working hours >10 hours were risk factors of job burnout, high subjective support and utilization of support were the protective factors of job burnout. CONCLUSION: The situation of job burnout in rural preschool teachers in Sichuan Province is not serious, post status, daily work hours and social support can affect their job burnout.

Objective To investigate the application value of sperm nucleoprotein immaturity and sperm DNA damage detection in in vitro fertilization(IVF).Methods From Mar.2015 to Feb.2016,routine sperm analysis,sperm nucleoprotein immaturity and sperm DNA damage detection were performed in 102 patients with infertility,and the correlation between these parameters were analyzed.Results Sperm DNA fragmentation rate was negatively correlated with IVF optimal embryos rate and sperm viability(P<0.05),while was not correlated with IVF fertility rate(P>0.05).Sperm nucleoprotein immaturity rate was not correlated with IVF optimal embryos rate and fertility rate(P>0.05),while was negatively correlated with sperm concentration(P<0.05).Conclusion Sperm DNA fragmentation rate could be closely correlated with IVF optimal embryos rate,which might be with prediction value in IVF treatment.

[Objective]Research on treatment based on syndrome differentiation of palmar hyperhidrosis(PH), for the purpose of systematically and comprehensively understanding PH, and to improve clinical curative effect. [Methods]The pathological basis, clinical manifestation and therapeutic principle and methods are systematically summarized.[Result]PH is relevant to the cold, heat, deficiency and excess of taste, disorder of Qi and blood of heart, and the block of damp and hot. Exuberant heat in Yangming, deficiency cold of spleen and stomach, and food stagnation can lead to PH. Malnutrition of heart spirit and dysfunction of heart caused by insufficiency of heart yin also contribute to PH. Another factor is the block of damp-heart. The treatment for PH caused by exuberant heat in Yangming is Baihu Decoction or Chengqi Decoctions. PH caused by deficiency cold of spleen and stomach can be cured by Lizhong Decoction. The treatment for PH caused by food stagnation is Baohe Wan. Insufficiency of heart yin and disharmony between Ying and Wei need to nourish blood for tranquillization and harmonize Ying and Wei. The block of damp or damp-heat leading to PH need drug resolving dampness with aromatics or clearing heat and promoting diuresis for cure. [Conclusion]PH has a complex pathogenesis, which needs treatment based on syndrome differentiation.

Aim To investigate the protective effect of cinnamic aldehyde ( CA ) on hormone-induced osteo-clasts proliferation and bone resorption in vitro and its molecular mechanisms. Methods RAW264. 7 cells induced into osteoclast were treated with RANKL and M-CSF and then were divided into control group, dexa-methasone ( DEX ) group and different doses of CA (11. 6, 23. 2, 46. 4 μg·L-1 ) groups. OCs were ob-served after tartrate resistant acid phosphatase( TRAP) staining. The cell proliferation was determined by MTT assay at different time points. The expression levels of TRACP5 b in cell cultured supernatants were measured by ELISA. RT-PCR technique was applied to examine the transcriptional levels of RANK and NFATc1 . Re-sults In MTT assay, the proliferation of osteoclasts stimulated by dexamethasone was promoted seriously compared with negative control group ( P < 0. 05 ) . Meanwhile, DEX could strengthen the content of TRACP5 b and up-regulate the expressions of RANK and NFATc1 mRNA. After administration of CA, the proliferation was inhibited, while the enhanced expres-sion of TRAP5b was reversed,and the over-expressions of RANK and NFATc1 mRNA were obviously down-regulated in a time-and-dose-dependent manner ( P <0. 05 ) . Conclusion The results suggest that CA in-hibits proliferation and bone resorption of osteoclast in-duced by DEX, which may be mediated by down-regu-lation of RANK and NFATc1 mRNA.

Objective:To investigate the role of dendritic cells(DC) in unexplained recurrent spontaneous abortion(URSA) and to study the effect and molecular mechanism of Traditional Chinese Medicine Shou Tai Decoction ( STD ) on URSA treatment by regulating the function of DC.Methods:30 cases of normal pregnancy women and 30 cases of URSA patients were taken as control group and URSA group respectively.URSA patients were treated with Shou Tai Decoction.Peripheral blood mononuclear cells were taken from both control group and URSA group before and after STD administration.The proportion of CD11c+HLA-DR+cells,CD11c+CD80+cells and CD11c+CD86+cells in peripheral blood were measured by flow cytometry.Moreover,the mRNA expression of HLA-DR,CD80,CD86 and Indoleamine2,3-dioxygenase( IDO) in venous blood were detected by RT-PCR assay.The protein expression of IDO was detected by Western blot.Furthermore, the cytokines, including IL-12p70 and IL-6, in the blood serum were measured by ELISA.Results:Compared with normal pregnancy women,the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 of URSA patients in peripheral blood were both increased significantly(P<0.05), while the mRNA and protein expression of IDO were decreased markedly(P<0.05).Additionally,the level of IL-12p70 and IL-6 in serum of URSA women were significantly increased ( P<0.01 ) .When compared with URSA patients before STD administration, the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 decreased significantly after STD administration ( P<0.05 ) , while the mRNA and protein expression of IDO increased markedly after STD administration(P<0.05).Meanwhile,compared with before STD administration,serum protein level of IL-12p70 and IL-6 of URSA patients decreased significantly after STD treatment ( P<0.01 ) .Conclusion: The changes of proportion and function of DC were involved in URSA.The regulatory effect of STD on DC proportion and function contribute to the treatment of URSA.

Objective To investigate the physical and mental development of small and appropriate for gestational age preterm infants in their early life. Methods This study recruited 220 preterm infants, who were discharged from our hospital and visited preterm following-up clinic at regular intervals from February 2009 to December 2012. All of those infants were divided into two groups based on whether their birth weight below 10th percentile for their gestational ages or not. Weights, lengths and head circumferences were measured up to seventh month age adjusted by gestational age. Meanwhile, mental tests were conducted by the professional staffs working on the children developmental assessment at their adjusted months of 5th, 6th or 7th. All of physical and mental scores were compared between the two groups. Results The SGA group was statistically less than the AGA group on the Z-score of weights from the ifrst to sixth month adjusted by gestational age (P<0.05). The difference disappeared on the seventh adjusted month age (P>0.05). The SGA group was statistically less than the AGA group on the Z-score of lengths from the ifrst to iffth month adjusted by gestational age (P<0.05). The difference disappeared on the sixth and seventh adjusted month age (P>0.05). The SGA group was statistically less than the AGA group on the Z-score of head circumferences from the ifrst to seventh month adjusted by gestational age (P<0.05). The SGA babies scored statistically less than the AGA babies with a mean development quotient score of 96.7 and 102.9, respectively (P<0.05). The scores of movement, cognitive, language in the SGA group were statistically less than those in the AGA group(P<0.05). Conclusions Preterm SGA could achieve satisfactory weight catch-up gain, with a decreasing difference from preterm AGA while they were getting older. But the length catch-up growth of preterm SGA seemed unsatisfactory with a big differece from preterm AGA. There was the worst catch-up on head circumference in those preterm SGA, backward in mental development, particularly in their movement, cognitive and language capacity.