1.Role of amino acid metabolism in autoimmune hepatitis and related therapeutic targets
Peipei GUO ; Yang XU ; Jiaqi SHI ; Yang WU ; Lixia LU ; Bin LI ; Xiaohui YU
Journal of Clinical Hepatology 2025;41(3):547-551
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear, but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system, while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH, in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.
2.Therapeutic effect of oral Xuefu Zhuyu Pill combined with intravitreal injection of Aflibercept in the treatment of retinal vein occlusion
Ran SHEN ; Hongying JI ; Hongyu CUI ; Lequan YANG ; Lixia GUO
International Eye Science 2025;25(9):1532-1536
AIM: To explore the therapeutic effect of oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of retinal vein occlusion(RVO).METHODS: A total of 80 patients(80 eyes)with RVO admitted to our hospital from January 2021 to March 2024 were prospectively selected. According to the treatment method, they were divided into a control group of 40 patients treated with intravitreal injection of aflibercept, and an observation group of 40 patients treated with oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept. The efficacy, TCM syndrome score, retinal microcirculation parameters, macular edema(ME), and adverse reactions were compared between the two groups of patients in the treatment of RVO.RESULTS: All patients have completed follow-up. The clinical effective rate of the observation group after treatment was 95%, obviously higher than that of the control group(80%; χ2=4.114, P=0.043). After treatment for 3 mo, the traditional Chinese medicine syndrome scores, foveal avascular area(FAZ)area, FAZ circumference, macular central retinal thickness, and neovascularization leakage area of both groups decreased, the overall blood flow density of the superficial capillary plexus(SCP)and deep capillary plexuses(DCP)increased, and the observation group showed better results than the control group(all P<0.05). There was no statistically significant difference in the occurrence of adverse reactions between the two groups during the treatment period(P>0.05).CONCLUSION: Oral administration of Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of RVO can improve retinal microcirculation, enhance vision, restore ocular blood circulation, improve bleeding, promote ME absorption, and improve clinical efficacy.
3.Extracellular vesicles: Roles in oocytes and emerging therapeutic opportunities.
Zhongyu ZHAO ; Yinrui SUN ; Renhao GUO ; Junzhi LIANG ; Wanlin DAI ; Yutao JIANG ; Yafan YU ; Yuexin YU ; Lixia HE ; Da LI
Chinese Medical Journal 2025;138(9):1050-1060
The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans
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Extracellular Vesicles/physiology*
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Oocytes/cytology*
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Female
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Animals
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Cell Communication/physiology*
4.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
5.Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease
Yuwen ZHAO ; Lixia QIN ; Hongxu PAN ; Tingwei SONG ; Yige WANG ; Xiaoxia ZHOU ; Yaqin XIANG ; Jinchen LI ; Zhenhua LIU ; Qiying SUN ; Jifeng GUO ; Xinxiang YAN ; Beisha TANG ; Qian XU
Chinese Medical Journal 2024;137(4):450-456
Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.
6.Diagnostic values of anti-salivary gland protein-1 antibody combined with anti-parotid secretory protein antibody for Sj?gren's syndrome
Yushu YANG ; Xuan QI ; Meng DING ; Wei WANG ; Huifang GUO ; Lixia GAO
Journal of Peking University(Health Sciences) 2024;56(5):845-852
Objective:To assess the diagnostic value of anti-salivary gland protein-1(SP1)antibody combined with anti-parotid secretory protein(PSP)antibody for Sj?gren's syndrome(SS).Methods:A total of 60 patients with primary SS(pSS)who were treated in the outpatient and inpatient department of Department of Rheumatology and Immunology of the Second Hospital of Hebei Medical University from January 2020 to December 2022 were collected.Thirty patients with other autoimmune diseases accompa-nied by dry mouth and/or dry eyes were collected as disease control group.Thirty healthy subjects from the physical examination center were collected for healthy control group,serum samples were obtained from all of them.Their general features and clinical information including clinical manifestations,labora-tory examinations and other examinations were recorded.The 2016 American College of Rheumatology(ACR)/European League against Rheumatism(EULAR)classification criteria were adopted as the diag-nostic standard of pSS.Immunoglobulin G(IgG)subtype of anti-SP1 antibody and anti-PSP antibody were detected by chemiluminescence immunoassay.The receiver operating characteristic(ROC)curve was used to evaluate the accuracy of anti-SP1 antibody and anti-PSP antibody in diagnosing pSS.The cli-nical characteristics of anti-SP1 antibody and anti-PSP antibody positive patients and negative patients in pSS group were further compared.Independent samples t test,Mann-Whitney U test,variance analysis,Kruskal-Wallis test,Chi-square test or Fisher's exact test and Spearman correlation analysis were used for statistical analysis.Results:There was no significant difference in age(F=1.406,P=0.495)and gender(x2=2.105,P=0.349)among pSS group,disease control group and healthy control group.The expression levels of anti-SP1 antibody(H=16.73,P<0.001)and anti-PSP antibody(H=26.09,P<0.001)were statistically different among the three groups.An intergroup comparison of anti-SP1 antibody expression levels showed that there was a statistically significant difference between pSS and healthy con-trol group(P<0.001),but no statistically significant difference between the other groups.Comparison of anti-PSP antibody expression levels between the groups showed that there were statistically significant differences between pSS and healthy control group(P<0.001),and between disease control group and healthy control group(P=0.009),while no statistically significant differences between the other groups.The positive rate of anti-SP1 antibody in pSS group was significantly higher than that in disease control group and healthy control group(58.33%vs.40.00%vs.13.33%,P<0.001).The positive rate of anti-PSP antibody in pSS group was significantly higher than that in disease control group and healthy control group(75.00%vs.56.17%vs.16.67%,P<0.001).The area under the curve for anti-SP1 antibody was 0.688(P<0.001).The sensitivity and specificity of anti-SP1 antibody were 58.33%(35/60)and 70.00%(42/60)respectively,the positive predictive value was 66.04%(35/53)and the negative predictive value was 54.55%(42/77)of anti-SP1 antibody.The area under the curve of anti-PSP antibody was 0.720(P<0.001),with a sensitivity was 75.00%(45/60),and spe-cificity was 63.33%(38/60).The positive predictive value and negative predictive value of anti-PSP an-tibody were 67.16%(45/67)and 71.70%(38/53)respectively.All the 13 pSS patients were negative for anti-Sjogren's syndrome A(SSA,including SSA52 and SSA60)antibody and anti-Sjogren's syn-drome B(SSB)antibody.Among them,11 patients were positive for both anti-SP1 antibody and anti-PSP antibody,1 patient was positive for anti-SP1 antibody and 1 patient was positive for anti-PSP anti-body.The clinical features of anti-SP1 antibody and anti-PSP antibody positive and negative groups were compared in pSS patients.The duration of disease in anti-SP1 antibody positive group was shorter(Z=-2.277,P=0.023)when compared with the negative patients.The patients with positive anti-PSP an-tibody were younger than those in the negative group(t=2.598,P<0.05),the positive rate of rheuma-toid factor(P=0.002)and the serum level of IgG(t=3.806,P=0.003)in anti-PSP antibody positive group were higher than in the negative group.Analysis of the correlation between anti-SP1 antibody and anti-PSP antibody in the pSS patients showed that there was significant correlation between them(r=0.801,P<0.001).Conclusion:Both anti-SP1 antibody and anti-PSP antibody are valuable in the diag-nosis of SS,and anti-SP1 antibody is helpful for the early diagnosis of pSS.The combined detection of anti-SP1 antibody and anti-PSP antibody is helpful for the early diagnosis of pSS patients with negative anti-SSA antibody and anti-SSB antibody.
7.Application value verification of fecal SDC2 gene methylation detection in intestinal cancer screening
Lixia GUO ; Zhiqin ZHANG ; Min GONG ; Fanghua XU
Chongqing Medicine 2024;53(20):3095-3099
Objective To verify the diagnostic efficiency and application value of fecal syndecan 2(SDC2)gene methylation detection in intestinal tumor screening.Methods The clinical data of 1 456 patients with fecal SDC2 gene methylation detection in this hospital from November 2021 to December 2023 were ana-lyze retrospectively.The detection positive rate,colonoscopic compliance,sensitivity,specificity,positive pre-dictive rate and negative predictive rate were analyzed.The pathological diagnosis served as the gold standard.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to judge the diagnostic effect.Results In the results in 1 456 cases of fecal SDC2 gene methylation detection,90 cases were positive with a positive rate of 6.2%.The positive rate had no statistical difference between different sexes(P>0.05).The positive rate in the patients ≥50 years old was higher than that in the patients<50 year old(P<0.05).Among 90 cases of detection results positive,67 cases completed the enteroscopic examination and the enteroscopic compliance rate was 74.4%.The enteroscopic compliance rate had no statistical difference be-tween the different sexes and among different ages of patients(P>0.05).Among 67 cases of enteroscopic ex-amination completion,there were 6 cases(9.0%)of colorectal cancer,17 cases(25.4%)of progressive stage adenoma,15 cases(22.4%)of non-progressive stage adenoma,6 cases(9.0%)of non-adenomatous polyp and the lesion detection rate was 65.7%.Among 112 cases of fecal SDC2 gene methylation detection negative,there were 2 cases(1.8%)of progressive stage adenoma and 22 cases(19.6%)of non-progressive stage ade-noma.The sensitivity and specificity of this detection for colorectal cancer and progressive stage adenoma were 92.0%and 71.4%,respectively,which had obvious diagnostic significance for colorectal tumor(AUC=0.721,P<0.001).Conclusion The fecal SDC2 gene methylation detection has an important clinical value in the preliminary screening of colorectal cancer.
8.Analysis of the influencing factors of abnormal blood pressure and electrocardiogram in occupational motor vehicle drivers
Yimu ZHENG ; Shuqiang LI ; Zanmei ZHAO ; Lixia GUO ; Yahong LI ; Li GUAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):821-825
Objective:To explore the influencing factors of abnormal blood pressure and electrocardiogram (ECG) in occupational motor vehicle drivers.Methods:In January 2024, a cluster sampling method was used to study 606 occupational motor vehicle drivers from a transportation service enterprise in Beijing who completed occupational health examination in 2023 in Peking University Third Hospital as observation group and 596 non-occupational motor vehicle drivers as control group. The data of personal history, occupational history, blood pressure and ECG were collected, and the effects of occupational motor vehicle driving on hypertension and ECG were analyzed by multivariate logistic regression.Results:The age of workers in the observation group was (34.1±7.8) years old, and the length of service was (7.0±7.1) years. The age of the control group was (33.8±7.6) years old, and the working age was (7.7±6.5) years. There was no significant difference in age and length of service between the two groups ( t=0.62, -1.90, P=0.538, 0.057). Systolic blood pressure (133.0±14.7) mmHg, diastolic blood pressure (83.7±11.6) mmHg, hypertension detection rate of 33.0% (200/606), ECG abnormality detection rate of 39.9% (242/606). They were significantly higher than those in the control group [ (127.8±14.4) mmHg, (77.5±11.0) mmHg, 24.7% (147/596), 31.0% (185/596) ], and the differences were statistically significant ( P<0.05). Multivariate logistic regression analysis showed that occupational motor vehicle driving were risk factors for hypertension and abnormal ECG ( OR= 1.210, 1.578; 95% CI: 1.145-1.231, 1.237-2.012; P<0.001) . Conclusion:Occupational motor vehicle driving may increase the risk of hypertension and abnormal ECG in workers.
9.Analysis of the influencing factors of abnormal blood pressure and electrocardiogram in occupational motor vehicle drivers
Yimu ZHENG ; Shuqiang LI ; Zanmei ZHAO ; Lixia GUO ; Yahong LI ; Li GUAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):821-825
Objective:To explore the influencing factors of abnormal blood pressure and electrocardiogram (ECG) in occupational motor vehicle drivers.Methods:In January 2024, a cluster sampling method was used to study 606 occupational motor vehicle drivers from a transportation service enterprise in Beijing who completed occupational health examination in 2023 in Peking University Third Hospital as observation group and 596 non-occupational motor vehicle drivers as control group. The data of personal history, occupational history, blood pressure and ECG were collected, and the effects of occupational motor vehicle driving on hypertension and ECG were analyzed by multivariate logistic regression.Results:The age of workers in the observation group was (34.1±7.8) years old, and the length of service was (7.0±7.1) years. The age of the control group was (33.8±7.6) years old, and the working age was (7.7±6.5) years. There was no significant difference in age and length of service between the two groups ( t=0.62, -1.90, P=0.538, 0.057). Systolic blood pressure (133.0±14.7) mmHg, diastolic blood pressure (83.7±11.6) mmHg, hypertension detection rate of 33.0% (200/606), ECG abnormality detection rate of 39.9% (242/606). They were significantly higher than those in the control group [ (127.8±14.4) mmHg, (77.5±11.0) mmHg, 24.7% (147/596), 31.0% (185/596) ], and the differences were statistically significant ( P<0.05). Multivariate logistic regression analysis showed that occupational motor vehicle driving were risk factors for hypertension and abnormal ECG ( OR= 1.210, 1.578; 95% CI: 1.145-1.231, 1.237-2.012; P<0.001) . Conclusion:Occupational motor vehicle driving may increase the risk of hypertension and abnormal ECG in workers.
10.Association of intestinal microecology with the development and progression of autoimmune hepatitis
Yuyan XIA ; Qiongrong ZENG ; Fujian LI ; Fengyan LI ; Qi LI ; Lixia TANG ; Guo ZHANG
Journal of Clinical Hepatology 2024;40(2):374-379
Autoimmune hepatitis (AIH) is an autoimmune disease characterized by chronic liver inflammation, with a gradually increasing incidence rate, and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years, it has been believed that changes in intestinal microecology can cause changes in autoimmune state, microbial metabolites, and intestinal barrier, which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients, elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH, and briefly describes related treatment regimens from the perspective of intestinal microecology, so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis, diagnosis, and treatment of AIH.

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