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.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.
6.Summary of best evidence for assessment and management of pain in perioperative patients with acute aortic dissection
Yi ZHANG ; Lin ZHANG ; Yueming OU ; Shanshan LU ; Qiu'e XU ; Xiaoxia TANG ; Jinhua GUO ; Jiaxi HUANG ; Lixia LIN ; Tiemei SHEN ; Hong CUI
Modern Clinical Nursing 2024;23(7):83-93
Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.
7.Novel mutations of AMHR2 in two families with persistent Müllerian duct syndrome
Lixia WANG ; Xiaoyu LI ; Yaru XU ; Jingzi WANG ; Haobo ZHU ; Jun DONG ; Yunfei GUO ; Yongji DENG
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):465-468
Persistent Müllerian duct syndrome(PMDS) is a rare disorder that arises from a lack of active anti-Müllerian hormone(AMH) or type Ⅱ AMH receptor(AMHR2) deficiency in males with a normal 46, XY chromosome karyotype.It presents that the external genitalia appears normally while the Müllerian duct structure(uterus, fallopian tubes, upper vagina) persists in the body.Common pathogenic factors are mutations in the AMH and AMHR2 genes, inherited in an autosomal recessive manner.This study reported two families with PMDS.The first patient was diagnosed with PMDS due to cryptorchidism in May 2019.Gene sequencing analysis revealed a new missense mutation(c.579G>T; p.W193C) and a splicing mutation(c.622-3C>A; splicing) in the AMHR2 gene.His father had the missense mutation(c.579G>T; p.W193C), and his mother had the splicing mutation(c.622-3C>A; splicing).The second patient was diagnosed with PMDS due to bilateral cryptorchidism, transverse testis ectopia in the right testicle in March 2023.Undegraded Müllerian tube derivatives were found between the two testicles, and serum AMH levels were very high(565.00 μg/L).Gene sequencing analysis reported that the AMHR2 gene had a new deletion mutation(c.835_837del; p.Leu279del).Both his father and mother had a deletion mutation(c.835_837del; p.Leu279del).This study reports two new AMHR2 gene mutations that expand the mutation sites of this rare disease.It is recommended to consider PMDS in the differential diagnosis of cryptorchidism, undergo surgery as early as possible, and treat Müllerian duct derivatives based on individual anatomical characteristics.
8.Proanthocyanidins promotes neurite outgrowth of dorsal root ganglion neurons in rat
Yingxiu CHEN ; Yingqi GUO ; Huimei ZHANG ; Qi ZHANG ; Jinkun WEN ; Li LUO ; Lixia LI
The Journal of Practical Medicine 2024;40(10):1357-1363
Objective To investigate the effect of proanthocyanidins(PC)on the neurite outgrowth of rat dorsal root ganglion(DRG)neurons.Methods In vitro,primary rat DRG neurons were cultured wtih a series of concenteation of PC to assess the effect of PC on the number and length of neurites as well as the morphology of growth cone.In vivo,the expression of growth associated protein 43(GAP43)in the early stage of injury was detected using the sciatic nerve crush model.Finally,the impact of PC on nerve growth factor(NGF)expression in DRG neurons was evaluated in vitro using immunofluorescence and ELISA.Results PC significantly increased the number and length of neurites and the number of pseudopodium in growth cones of DRG neurons.PC also promoted the expres-sion of GAP43 in the early stage of sciatic nerve injury in rats and enhanced the expression of NGF in DRG neurons.Conclusion PC may promote the neurite outgrowth by increasing the expression of NGF in DRG neurons.
9.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.
10.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.

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