1.Exploratory Study on the Impact of Intestinal Fungi on the Progression of Heart Failure in Patients with Chronic Kidney Disease
Shuting LI ; Lili DONG ; Xinlei YANG ; Lin LYU ; Fukai LIU
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1236-1243
To investigate the role of intestinal fungi in the progression of heart failure (HF) associated with chronic kidney disease (CKD). This study consisted of two parts. The first part was a clinical study. Fecal samples from CKD patients (CKD group), CKD patients with HF (CKD+HF group), and healthy individuals (healthy control group) were subjected to 18S rRNA sequencing to compare differences in intestinal fungal microbiota among the three groups. The second part was an animal experiment. Male C57BL/6J mice were randomly divided into a control group (fed a standard diet), a CKD group (fed a 0.2% adenine diet), and a CKD+amphotericin B group (fed a 0.2% adenine diet+0.5 mg/L amphotericin B in drinking water), with 10 mice in each group. After successful modeling, cardiac function and histomorphological differences among the three groups were compared by assessing exercise tolerance, left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and histological examinations (HE staining and Masson staining) of cardiac tissue. The clinical study revealed that compared with the healthy control group ( Intestinal fungi may be associated with the progression of HF in CKD patients. Depletion of intestinal fungi could potentially ameliorate cardiac remodeling and delay the onset and progression of HF. Intestinal fungi may serve as a novel therapeutic target for HF in CKD patients.
2.Application of Photoplethysmography Combined with Deep Learning in Postoperative Monitoring of Flaps
Jing YANG ; Xinlei YANG ; Yuwei GAO ; Chunlei ZHANG ; Di WANG ; Tao SONG
Chinese Journal of Medical Instrumentation 2024;48(4):419-425
Objective Photoelectric volumetric tracing(PPG)exhibits high sensitivity and specificity in flap monitoring.Deep learning(DL)is capable of automatically and robustly extracting features from raw data.In this study,we propose combining PPG with 1D convolutional neural networks(1D-CNN)to preliminarily explore the method's ability to distinguish the degree of embolism and to localize the embolic site in skin flap arteries.Methods Data were collected under normal conditions and various embolic scenarios by creating vascular emboli in a dermatome artery model and a rabbit dermatome model.These datasets were then trained,validated,and tested using 1D-CNN.Results As the degree of arterial embolization increased,the PPG amplitude upstream of the embolization site progressively increased,while the downstream amplitude progressively decreased,and the gap between the upstream and downstream amplitudes at the embolization site progressively widened.1D-CNN was evaluated in the skin flap arterial model and rabbit skin flap model,achieving average accuracies of 98.36%and 95.90%,respectively.Conclusion The combined monitoring approach of DL and PPG can effectively identify the degree of embolism and locate the embolic site within the skin flap artery.
3.Gene expression profile in human cervical epithelial cells infected with Chlamydia trachomatis
Ru JIA ; Chenli SI ; Mingyang LI ; Jia YANG ; Xinlei WU ; Shanli ZHU
Chinese Journal of Microbiology and Immunology 2023;43(2):93-101
Objective:To compare gene expression profiles in normal human cervical epithelial cells (HcerEpic) before and after Chlamydia trachomatis ( Ct) infection. Methods:HcerEpic cells that were pretreated with DEAE-D were infected with Ct serotype E standard strain and then cultured for 44 h. Uninfected HcerEpic cells were used as the control group. Total RNA was extracted from the cells in each group and reverse transcribed to construct a cDNA library. Differences in gene expression profiles between the two groups were analyzed by high-throughput sequencing and the representative genes were selected for verification by qPCR. Results:A total of 23 997 genes were detected, including 125 differentially expressed genes. Among the 125 genes, 119 were up-regulated and six were down-regulated. GO analysis showed that the differentially expressed genes were enriched in several biological processes including defense response to virus, typeⅠinterferon signaling pathway and cellular responses to typeⅠinterferons. KEGG enrichment analysis showed the differentially expressed genes were mainly enriched in the pathways related to virus infections, such as influenza A virus, herpes simplex virus, EB virus and HPV, and NOD-like receptor pathway.Conclusions:There were significant differences in transcriptome profiles of HcerEpic cells before and after Ct infection. The differentially expressed genes were mainly enriched in the interferon pathway, which was closely related to the antiviral processes in cells. qPCR verified the differentially expressed genes and the genes closely related to the interferon pathway, such as ISG15, IFIT2, OASL and UBE2L6.
4.Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway.
Qiong LI ; Naya MA ; Xinlei LI ; Chao YANG ; Wei ZHANG ; Jingkang XIONG ; Lidan ZHU ; Jiali LI ; Qin WEN ; Lei GAO ; Cheng YANG ; Lingyi RAO ; Li GAO ; Xi ZHANG ; Jun RAO
Chinese Medical Journal 2023;136(12):1448-1458
BACKGROUND:
Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.
METHODS:
The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.
RESULTS:
We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .
CONCLUSION
Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans
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Animals
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Mice
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Rituximab/therapeutic use*
;
Hippo Signaling Pathway
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Lymphoma, Large B-Cell, Diffuse/pathology*
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Prognosis
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Semaphorins/therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Membrane Proteins/genetics*
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Nerve Tissue Proteins/genetics*
5.Preliminary Construction of Evaluation Index System for Traditional Chinese Medicine Medicated Diet based on Delphi Method and Analytic Hierarchy Process
Jixin LI ; Linjie QIU ; Yan REN ; Meijie LI ; Wenjie LI ; Xinlei DU ; Wenru WANG ; Kai YANG ; Jin ZHANG
Journal of Traditional Chinese Medicine 2023;64(23):2412-2418
ObjectiveTo build an evaluation index system for traditional Chinese medicine (TCM) medicated diet, promoting the scientific and standardized development of medicated diet in TCM. MethodsThe framework of the evaluation index system was constructed through literature review and Delphi expert consultation method. The analytic hierarchy process was used to construct a hierarchical structure model. Pairwise comparisons between the indicators were conducted using the Saaty 1-9 scale method, and the weight of each indicator was calculated using Yaahp 10.3. ResultsThe response rates for the two rounds of expert consultation were 93.33% and 100%, respectively. The Kendall's W coefficients for the first-level and second-level indicators in the second round were 0.270 and 0.281, respectively (both P<0.001). Finally, an evaluation index system for TCM medicated diet therapy was constructed, consisting of 6 primary indicators and 27 secondary indicators. The weightings of the primary indicators were as follows: sensory appearance (0.1843), health value (0.3569), ingredient compatibility (0.1271), packaging (0.0370), production and preparation (0.1005), and reliability (0.1940). ConclusionA comprehensive and universally applicable evaluation index system for TCM medicated diet has been developed, taking into conside-rations of color, taste, appearance, efficacy, preparation, quality and others. This system can provide valuable reference for the evaluation of the value of medicated diet as well as its development.
6.OShnscc: a novel user-friendly online survival analysis tool for head and neck squamous cell carcinoma based on RNA expression profiles and long-term survival information.
Guosen ZHANG ; Qiang WANG ; Xinlei QI ; Huimin YANG ; Xiaodong SU ; Manman YANG ; Chao JIANG ; Yang AN ; Hong ZHENG ; Lu ZHANG ; Wan ZHU ; Jiancheng GUO ; Xiangqian GUO
Journal of Zhejiang University. Science. B 2022;23(3):249-257
Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
Biomarkers, Tumor/genetics*
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Head and Neck Neoplasms/genetics*
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Humans
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Kaplan-Meier Estimate
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RNA
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Squamous Cell Carcinoma of Head and Neck
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Survival Analysis
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Survival Rate
7.Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes
Jie ZHUYE ; Chen CHEN ; Hao LILAN ; Li FEI ; Song LIJU ; Zhang XIAOWEI ; Zhu JIE ; Tian LIU ; Tong XIN ; Cai KAIYE ; Zhang ZHE ; Ju YANMEI ; Yu XINLEI ; Li YING ; Zhou HONGCHENG ; Lu HAORONG ; Qiu XUEMEI ; Li QIANG ; Liao YUNLI ; Zhou DONGSHENG ; Lian HENG ; Zuo YONG ; Chen XIAOMIN ; Rao WEIQIAO ; Ren YAN ; Wang YUAN ; Zi JIN ; Wang RONG ; Liu NA ; Wu JINGHUA ; Zhang WEI ; Liu XIAO ; Zong YANG ; Liu WEIBIN ; Xiao LIANG ; Hou YONG ; Xu XUN ; Yang HUANMING ; Wang JIAN ; Kristiansen KARSTEN ; Jia HUIJUE
Genomics, Proteomics & Bioinformatics 2022;20(2):304-321
The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
8.Simultaneous Determination of 7 Effective Components in Yao Medicine Yueli Yaomi Spray by QAMS
Jingzhi ZHANG ; Danqing ZHAO ; Zhengrong WANG ; Jinyan JIA ; Lin YANG ; Shengsheng ZHANG ; Xinlei LIU ; Qing WU ; Wei PAN
China Pharmacy 2020;31(9):1044-1049
OBJECTIVE:To establish QAMS method for simultaneou s determination of 7 effective components in Yao medicine Yueli yaomi spray ,such as α-cyperone,α-pinene,β-pinene,limonene,β-elemene,caryophyllene oxide and ligustilide , so as to provide method reference for the quality control of the preparation. METHODS :GC method was adopted. The determination was performed on DB- 1701P capillary column ,using nitrogen as carrier gas. The temperature of the hydrogen flame ion detector was 240 ℃. The temperature was programmed ,the inlet temperature was 240 ℃,the injection volume was 1 μL and the split ratio was 20 ∶ 1. Using limonene as internal reference ,the relative correction factors of other 6 components were calculated,the contents of them were calculated with relative correction factors ,and then compared with the results of internal standard method (using naphthalene as internal standard ). RESULTS :The mass concentration linear range of α-cyperone, α-pinene,β-pinene,limonene,β-elemene,caryophyllene oxide and ligustilide were 0.008 9-1.110 0,0.028 3-3.540 0,0.020 5- 2.560 0,0.023 0-2.880 0,0.016 3-2.035 0,0.013 1-1.640 0,0.008 3-1.040 0 mg/mL(all r>0.999 0);the limits of quantification were 0.005 6,0.013 1,0.011 4,0.018 6,0.010 8,0.008 9,0.004 5 mg/mL;the detection limits were 0.001 9,0.004 1,0.003 7, 0.006 2,0.003 5,0.002 9,0.001 5 mg/mL;RSDs for precision ,stability(24 h),and repeatability tests were all less than 2% (n=5 or n=6); the average recoveries were 98.48% , 014) 101.37%,97.96%,99.80%,102.79%,97.77%,102.14%, and RSDs were all lower than 2%(n=9),respectively. The average relative correction factors of α-cyperone,α-pinene, β-pinene,β-elemene,caryophyllene oxide and ligustilide were 1.045 8,0.621 0,0.488 5,0.382 9,0.708 9,0.956 9 respectively,and the RSDs were all lower than 2%(n=6). There wa s no statistical significance in contents of 7 components between QAMS method and internal standard method (P>0.05). CONCLUSIONS :The established QAMS method is simple , accurate,stable and reproducible ,and can be used for simultaneous determination for 7 components in Yueli yaomi spray.
9.Study on Metabolic Transformation of Total Glycosides of Cistanche deserticola in Artificial Gastric and Intestinal Juice
Xinlei WANG ; Bonan LIU ; Mengmeng ZHANG ; Guiyu LIU ; Yang HU ; Xiangming SUN ; Wenlan LI
China Pharmacy 2020;31(1):53-61
ABSTRACT OBJECTIVE:To study the metabolic transformation of total glycosides of Cistanche deserticola in artificial gastric and intestinal juice,and to speculate its metabolic transformation pathway in vivo. METHODS:UPLC/Q-TOF-MS was adopted. The determination was performed on ACQUITY UPLC BEH column with mobile phase consisted of 0.2% formic acid water-acetonitrile(gradient elution)at the flow rate of 0.2 mL/min. The detection wavelength was set at 330 nm,and column temperature was 25 ℃. The ion source was electrospray ion source,and mass to charge ratio(m/z)was 50→1 000. In the positive and negative ion mode,the metabolic components of the total glycosides of C. deserticola in artificial gastric and intestinal juice were identified analysis,and combined with the literature,the metabolic pathway of total glycosides of C. deserticola in artificial gastric and intestinal juice was speculated. RESULTS:After the total glycosides of C. deserticola were metabolized by artificial gastric juice,and a total of 69 components were estimated,including 14 prototype components (such as Mustard aldehyde glucoside,daucosstorol) and 55 metabolic components (such as Methyl-O-Kankanoside J,Methyl-O-Kankanoside E),it is speculated that its metabolic pathways were methylation,demethylation,hydroxylation,methoxylation,acetylation,sulfation,and glucuronidation. After the total glycosides of C. deserticola were metabolized by artificial intestinal juice,a total of 90 components were estimated,including 4 prototype components(such as Kankanoside M,Kankanoside L)and 86 metabolic components(such as Methyl-O-Kankanoside, Methyl-O-Kankanoside E). It was speculated that its metabolic pathways were methylation, demethylation,hydroxylation,dehydroxylation,methoxylation,acetylation,sulfation and glucuronidation. CONCLUSIONS:This study preliminarily speculates that the total glycosides of C. deserticola may be metabolized by methylation,demethylation, hydroxylation and other metabolic pathway in artificial gastrointestinal juice,which may provide reference for the in vivo metabolic transformation of total glycosides of C. deserticola.
10.PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells.
Gulnara TUGUZBAEVA ; Er YUE ; Xi CHEN ; Lina HE ; Xinlei LI ; Jiaming JU ; Ying QIN ; Valentin PAVLOV ; Yanjie LU ; Wenting JIA ; Yunlong BAI ; Yumei NIU ; Baofeng YANG
Acta Pharmaceutica Sinica B 2019;9(6):1163-1173
Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

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