1.LSS deficiency ameliorates MASLD by downregulating NPC1L1 and activating the CD36/TLR4/JNK pathway
Zihan WANG ; Hongmei BAI ; Qingya HE ; Wenjing ZHOU ; Jian ZHONG ; Xiaoli JIANG ; Sumei ZHANG ; Shengquan ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(5):812-818
ObjectiveTo investigate whether intestinal deficiency of lanosterol synthase (LSS), a key enzyme in cholesterol synthesis, influences the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal cholesterol absorption and immune response. MethodsLSS heterozygous knockout (LSS+/-) mice and wild-type (WT) controls were generated using CRISPR/Cas9 technology and fed either a high-fat diet (HFD) or regular chow (CHOW). The model was validated by genotyping. Hepatic steatosis was assessed by HE and oil red O staining. Immunohistochemistry was used to detect the localization and expression of NPC1L1 and CD36 proteins in the intestine. Western blot analysis was performed to measure JNK phosphorylation and TLR4 protein levels in intestinal tissues. Real-time quantitative polymerase chain reaction (qPCR) was employed to examine the mRNA expression of TLR4 and IL-6. ResultsLSS+/- mice were successfully validated by genotyping and reduced intestinal LSS protein expression. HE and oil red O staining of liver sections showed that, compared with WT mice fed a CHOW diet, WT mice fed a HFD exhibited a marked increase in hepatic lipid vacuoles. In contrast, compared with HFD-fed WT mice, HFD-fed LSS+/- mice displayed significantly attenuated hepatic lipid deposition and reduced serum ALT levels (P<0.05). Immunohistochemical analysis revealed that, compared with WT mice, the expression of the cholesterol absorption protein NPC1L1 in the intestinal villi of LSS+/- mice was downregulated under both CHOW and HFD conditions (PHFD<0.001). Conversely, the expression of the fatty acid transporter CD36 was upregulated in the intestines of LSS+/- mice (PCHOW<0.05, PHFD<0.01). Western blot analysis demonstrated that, compared with WT mice, TLR4 protein expression in the intestines of LSS+/- mice significantly increased under both CHOW and HFD conditions (both P<0.05). JNK phosphorylation level was significantly elevated in LSS+/- mice under CHOW condition (both P<0.05). Under HFD condition, total JNK protein expression increased, but its phosphorylation level showed no significant change. qPCR analysis showed that, compared with WT mice, the mRNA levels of TLR4 (PCHOW<0.01, PHFD<0.000 1) and IL-6 (PCHOW<0.001, PHFD<0.01) were significantly upregulated in the intestines of LSS+/-mice. ConclusionLSS deficiency counteracts hepatic lipid deposition by orchestrating a synergistic reprogramming involving restricted intestinal cholesterol absorption, enhanced fatty acid utilization, and activation of immune pathways, suggesting intestinal LSS as a potential therapeutic target of MASLD.
2.Opportunities and Challenges of Artificial Intelligence Assisted Blood Cell Morphology Examination
Xinrui FENG ; Weiru WU ; Xiaoli ZHANG ; Zhong YANG ; Qinghua BI
Journal of Modern Laboratory Medicine 2025;40(1):189-195
Blood cell morphology examination is the foundation and important means of diagnosing blood diseases. Artificial intelligence (AI) assisted blood cell morphology examination compensates for the shortcomings of artificial microscopy in the early detection and diagnosis of blood diseases,improves diagnostic efficiency,accuracy,and sensitivity,greatly reduces labor and time costs,significantly improves medical quality,and promotes personalized health care. Traditional manual microscopy is still the standard method in clinical practice in China. In order to encourage the improvement and development of intelligence-assisted blood cell morphology examination,this article discusses the current situation and characteristics of intelligence-assisted blood cell morphology examination. Considering the standardization,database,and ethical issues of automated blood cell morphology analysis,some challenges and limitations are summarized and analyzed,which can support the diagnosis of blood diseases and assist researchers and clinical doctors in the future.
3.Endoscopic ultrasound-guided coil combined with tissue glue embolization for the treatment of visceral artery pseudoaneurysm (with video)
Guanjun KOU ; Jingran SU ; Xiaoli JIA ; Ning ZHONG
Chinese Journal of Digestive Endoscopy 2025;42(7):569-572
To investigate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil combined with tissue glue embolization for visceral arterial pseudoaneurysms (VAPA), clinical data of 4 patients who underwent this procedure at the Endoscopy Center of Qilu Hospital, Shandong University between June 2024 and March 2025 were retrospectively analyzed. Parameters including technical success rate, procedure time, postoperative complications, costs, and postoperative hospital stay were recorded. The technical success rate was 100%, with embolization time ranging from 100 seconds to 260 seconds. No severe complication occurred in any patient. The procedure costs varied between 7.6 thousand yuan and 13.6 thousand yuan, with postoperative hospitalization lasting 2-3 days. During the follow-up period of 2.0-11.0 months, no VAPA recurrence was observed in any case. This preliminary study demonstrates that EUS-guided coil combined with tissue glue may represent a feasible and safe novel therapeutic approach for VAPA. It is worth clinical application for no radiation, minimal invasiveness, short procedure time and cost-effectiveness .
4.Latent profile analysis and its influencing factors of health promotion behavior of patients after PCI
Yuxin LI ; Jijun WU ; Xiaoli ZHONG ; Fangming ZHOU ; Ping DAI ; Yuting FAN ; Lin HE
Modern Clinical Nursing 2025;24(6):32-41
Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.
5.Latent profile analysis and its influencing factors of health promotion behavior of patients after PCI
Yuxin LI ; Jijun WU ; Xiaoli ZHONG ; Fangming ZHOU ; Ping DAI ; Yuting FAN ; Lin HE
Modern Clinical Nursing 2025;24(6):32-41
Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.
6.Effects of macrophage migration inhibitory factor on survival,proliferation,and differentiation of human embryonic stem cells
Ting HUANG ; Xiaohan ZHENG ; Yuanji ZHONG ; Yanzhao WEI ; Xufang WEI ; Xudong CAO ; Xiaoli FENG ; Zhenqiang ZHAO
Chinese Journal of Tissue Engineering Research 2025;29(7):1380-1387
BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.
7.Construction and feasibility of a full chain follow-up system for tumor patients at chemotherapy stage
Lin TAN ; Xiaoli ZHONG ; Jijun WU ; Furong JIANG ; Yao LIU ; Lin HE
Chinese Journal of Nursing 2025;60(2):177-184
Objective To establish a full-chain follow-up system for tumor patients during chemotherapy and to evaluate its application effect.Methods A full-chain follow-up system was built according to the actual needs of cancer patients during chemotherapy,including 5 modules:patient health records,follow-up plan,risk identification and abnormal reminder,online consultation,interaction between doctors and patients and data visualization analysis and intelligent statistical management.Convenience sampling method was used to select 96 patients with tumor at chemotherapy stage who were treated in a tertiary A hospital in Deyang City,Sichuan Province from February to June 2023 as a test group,and the full chain follow-up system for tumor patients at chemotherapy stage was applied for follow-up;93 patients with tumor at chemotherapy stage were treated from February to June 2022 as a control group for routine follow-up care.Indicators of self-management ability,quality of life and satisfaction with follow-up services were compared between the 2 groups before and after the application of the system.Results 94 cases in the test group and 92 cases in the control group completed the study.After the application of the system,the test group scored(169.44±11.96)on the Cancer Patients Self-Management Scale,higher than(150.76±13.44)in the control group.The score on the Cancer Patients Quality of Life Core Scale was(65.50±7.90),higher than(59.81±7.27)in the control group.The score on the Questionnaire of Satisfaction with the Follow-Up Service was(52.00±3.30),higher than(48.89±3.54)in the control group,and the difference between the 2 groups was statistically significant(P<0.001).Conclusion The application of the full-chain follow-up system can meet the diversified and multi-level follow-up needs of tumor patients during chemotherapy,achieve accurate,professional and intelligent nursing follow-up services,effectively improve patients'symptom self-management ability and quality of life,and improve patients'satisfaction with nursing services.
8.Opportunities and Challenges of Artificial Intelligence Assisted Blood Cell Morphology Examination
Xinrui FENG ; Weiru WU ; Xiaoli ZHANG ; Zhong YANG ; Qinghua BI
Journal of Modern Laboratory Medicine 2025;40(1):189-195
Blood cell morphology examination is the foundation and important means of diagnosing blood diseases. Artificial intelligence (AI) assisted blood cell morphology examination compensates for the shortcomings of artificial microscopy in the early detection and diagnosis of blood diseases,improves diagnostic efficiency,accuracy,and sensitivity,greatly reduces labor and time costs,significantly improves medical quality,and promotes personalized health care. Traditional manual microscopy is still the standard method in clinical practice in China. In order to encourage the improvement and development of intelligence-assisted blood cell morphology examination,this article discusses the current situation and characteristics of intelligence-assisted blood cell morphology examination. Considering the standardization,database,and ethical issues of automated blood cell morphology analysis,some challenges and limitations are summarized and analyzed,which can support the diagnosis of blood diseases and assist researchers and clinical doctors in the future.
9.Therapeutic efficacy and mechanism of artesunate for mouse model of polycystic ovary syndrome
Xueling WANG ; Peiling ZHONG ; Zhipeng ZHAO ; Fei CHEN ; Xin LIU ; Sijia LIU ; Lie YUAN ; Lu FANG ; Qianyi YAO ; Xiong YANG ; Chao LIU ; Jiakun CHENG ; Yongqing CAI ; Xiaoli LI ; Weihong LI
Journal of Army Medical University 2025;47(3):193-204
Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P<0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P<0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P<0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P<0.05),and reduced HOMA-IR,TC and TG levels(P<0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P<0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.
10.p300 promotes hepatic lipid accumulation in dyslipidemia by regulating SREBP-1c acetylation
Nyewneh Abdul-Rauf NUHU ; Xiaoli LI ; Lu FANG ; Yongqing CAI ; Fei CHEN ; Lie YUAN ; Xiong YANG ; Qingsong JIANG ; Yinbo LIU ; Chao LIU ; Peiling ZHONG ; Menghua ZENG
Journal of Army Medical University 2025;47(22):2735-2748
Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

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