1.MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis.
Chao HOU ; Dong WANG ; Mingxia ZHAO ; Petek BALLAR ; Xinru ZHANG ; Qiong MEI ; Wei WANG ; Xiang LI ; Qiang SHENG ; Jun LIU ; Chuansheng WEI ; Yujun SHEN ; Yi YANG ; Peng WANG ; Juntang SHAO ; Sa XU ; Fuyan WANG ; Yang SUN ; Yuxian SHEN
Acta Pharmaceutica Sinica B 2023;13(10):4234-4252
The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.
2.Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis.
Ya WANG ; Meng Yue HOU ; Yao FU ; Kui MENG ; Hong Yan WU ; Jin CHEN ; Yue Mei XU ; Jiong SHI ; Xiang Shan FAN
Chinese Journal of Pathology 2023;52(4):358-363
Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
Humans
;
Kidney Neoplasms/pathology*
;
Carcinoma, Renal Cell/pathology*
;
Diagnosis, Differential
;
Angiomyolipoma/diagnosis*
;
Biomarkers, Tumor/metabolism*
;
Leukemia, Myeloid, Acute/diagnosis*
;
Membrane Glycoproteins
3.Development of a Recombinase-aided Amplification Combined With Lateral Flow Dipstick Assay for the Rapid Detection of the African Swine Fever Virus.
Jiang Shuai LI ; Yan Zhe HAO ; Mei Ling HOU ; Xuan ZHANG ; Xiao Guang ZHANG ; Yu Xi CAO ; Jin Ming LI ; Jing MA ; Zhi Xiang ZHOU
Biomedical and Environmental Sciences 2022;35(2):133-140
OBJECTIVE:
To establish a sensitive, simple and rapid detection method for African swine fever virus (ASFV) B646L gene.
METHODS:
A recombinase-aided amplification-lateral flow dipstick (RAA-LFD) assay was developed in this study. Recombinase-aided amplification (RAA) is used to amplify template DNA, and lateral flow dipstick (LFD) is used to interpret the results after the amplification is completed. The lower limits of detection and specificity of the RAA assay were verified using recombinant plasmid and pathogenic nucleic acid. In addition, 30 clinical samples were tested to evaluate the performance of the RAA assay.
RESULTS:
The RAA-LFD assay was completed within 15 min at 37 °C, including 10 min for nucleic acid amplification and 5 minutes for LFD reading results. The detection limit of this assay was found to be 200 copies per reaction. And there was no cross-reactivity with other swine viruses.
CONCLUSION
A highly sensitive, specific, and simple RAA-LFD method was developed for the rapid detection of the ASFV.
African Swine Fever/virology*
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African Swine Fever Virus/isolation & purification*
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Animals
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Nucleic Acid Amplification Techniques/methods*
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Recombinases/chemistry*
;
Sensitivity and Specificity
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Swine
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Viral Proteins/genetics*
4.Clinical application of serum Golgi protein 73 in patients with chronic liver diseases.
Yan Na LIU ; Ming Jie YAO ; Su Jun ZHENG ; Xiang Mei CHEN ; Xiang Yi LIU ; Peng HU ; Qi Shui OU ; Xiao Guang DOU ; Hong Song CHEN ; Zhong Ping DUAN ; Jin Lin HOU ; Yue Min NAN ; Zhi Liang GAO ; Xiao Yuan XU ; Hui ZHUANG ; Feng Min LU
Chinese Journal of Hepatology 2022;30(1):4-8
Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers
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Carcinoma, Hepatocellular
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Golgi Apparatus
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Humans
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Liver Cirrhosis
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Liver Neoplasms
5.Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis
Rui-hong ZHOU ; Xun-ya HOU ; Xiang-hui CHENG ; Jie PAN ; Ru-yi LAI ; Gui-mei CHEN ; Hui ZHANG ; Lan-jun WEI ; Lu ZHANG ; Jia-xin LIU
Chinese Journal of Schistosomiasis Control 2022;34(6):626-629
Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.
6.Establishment and internal validation of preoperative nomograms for predicting the possibility of testicular salvage in patients with testicular torsion.
Wan-Xiang ZHENG ; Guang-Dong HOU ; Wei ZHANG ; Di WEI ; Xue-Lin GAO ; Mei-Hong CHEN ; Lu-Guang HUANG ; Fei YAN ; Geng ZHANG ; Lei YU ; Fei LIU ; Bo ZHANG ; Jian-Lin YUAN
Asian Journal of Andrology 2021;23(1):97-102
This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration.
7.Investigation and Analysis of Traditional Chinese Medicine Syndromes with 144 Cases of COVID-19 Patients in Anhui Province
Jing ZHOU ; Jing-jing CHEN ; Nian-zhi ZHANG ; Xiao-xiao ZHU ; Jing LI ; Shi-qing WANG ; Yun-dong LI ; Ming-xiang HAN ; Wei CHEN ; Mei DONG ; Ling LIU ; Hao-bin HOU ; Zhen DING ; Xin-kuang LIU ; Li YAO
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(12):28-34
Objective:To analyze the general situation and traditional Chinese medicine (TCM) syndrome characteristics in patients with coronavirus disease-2019(COVID-19) in Anhui province, and to provide a basis for clinical diagnosis and treatment. Method:The 144 cases of COVID-19 patients in Anhui province were collected from designated hospitals by means of multi-center cross-sectional epidemiological survey. The TCM syndrome information collection table of patients with novel coronavirus pneumonia was created to collect the general data, etiology and pathogenesis, pulse and signs, syndrome type and frequency statistics of the patients, and then summarize and analyze the main symptoms and syndrome distribution characteristics of patients with novel coronavirus pneumonia. Result:The mean age of 144 patients with COVID-19 infection was (43.54±15.91) years old, and the number of males was larger than the number of females (9/7). The age distribution and gender difference of the patients were statistically significant (
8.A New Method for Ultra-sensitive P24 Antigen Assay Based on Near-infrared Fluorescent Microsphere Immunochromatography
Qi WANG ; Ling Mei HOU ; Peng Li LIU ; Jing MA ; Guang Xiao ZHANG ; Xiang Zhi ZHOU ; Xi Yu CAO
Biomedical and Environmental Sciences 2020;33(3):174-182
Objective To develop a rapid, highly sensitive quantitative method for detecting P24 antigen based on near-infrared fluorescent microsphere immunochromatography.Methods First, we prepared a lateral flow assay test strip, and labeled the detection antibody using a fluorescent microsphere. Second, we optimized the antibody labeling conditions. Third, we optimized the detection conditions. Fourth, we created a working curve. Fifth, we conducted a methodological assessment of the established fluorescent microsphere immunochromatography method. Sixty-six clinical samples were tested, and we compared the established fluorescent microsphere immunochromatography with the quantitative ELISA method. Results According to the working curve, the detection limit of the method is 3.4 pg/mL, and the detection range is 3.4 pg/mL to 10 ng/mL. The average intra-assay recovery was 99.6%, and the Coefficient of Variation (CV) was 5.4%–8.6%; the average inter-assay recovery was 97.3%, and the CV was 8.5%–11%. The detection rate of fluorescent microsphere immunochromatography was higher than ELISA method, and had a good correlation with ELISA. Conclusion The P24 antigen quantitative detection method based on near-infrared fluorescent microsphere immunochromatography has the advantages of rapid detection, high sensitivity, and wide detection range; thus, it is suitable for early clinical diagnosis and continuous monitoring of AIDS.
9.Cloning and expression of SmDXS2 gene in Swertia mussotii.
Wen-Jing LI ; Bei-Bei XIANG ; Yan-Xiang SUN ; Xiao-Qiang HOU ; Mei-Ling HAN ; Xiao-Xue LI ; Yong WANG ; Shuo GUO
China Journal of Chinese Materia Medica 2019;44(5):935-941
1-deoxy-D-xylulose-5-phosphate synthase2(DXS2) is the first key enzyme of the MEP pathway,which plays an important role in terpene biosynthesis of plants. According to the data of Swertia mussotii transcriptome, DXS2 gene(Gen Bank number MH535905) was cloned and named as Sm DXS2. The bioinformatics results showed that Sm DXS2 has no intron,with a 2 145 bp open reading frame encoding a polypeptide of 714 amino acids. They are belonging to 20 kinds of amino acids,and the most abundant amino acids include Ala,Gly and Trp. The predicted protein molecular weight was 76. 91 k Da and its theoretical isoelectric point(p I) was6. 5,which belonging to a hydrophilic protein. α-Helix and loop were the major motifs of predicted secondary structure of DXS2. The three function domains are TPP_superfamily,Transket_pyr_ superfamily and Transketolase_C superfamily,respectively. The Sm DXS2 protein shared high identity with other DXS2 proteins of plants. Phylogenetic analysis showed that Sm DXS2 protein is grouped with the gentian DXS2 protein. The recombinant protein of Sm DXS2 gene in Escherichia coli was approximately 92. 00 k Da(containing sumo-His tag protein 13 k Da),which was consistent with the anticipated size.This work will provide a foundation for further functional research of Sm DXS2 protein and increasing the product of iridoid compound by genetic engineering in S. mussotii.
Amino Acid Sequence
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Cloning, Molecular
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DNA, Complementary
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genetics
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Genes, Plant
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Iridoids
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Phylogeny
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Plant Proteins
;
genetics
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Swertia
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enzymology
;
genetics
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Transcriptome
;
Transferases
;
genetics
10.The study of salivary pepsin content and laryngopharyngeal reflux scale in 91 asymptomatic volunteers.
Mei Xiang CHEN ; Chen Jie HOU ; Ting CHEN ; Yan Ping LI ; Yan Ling ZENG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2018;32(6):415-419
OBJECTIVES:
To investigate the content of pepsin in salivary, and to assess the laryngophargeal lesions based on the reflux founding score (RFS) scale in asymptomatic volunteers, in order to provide a reference for the diagnosis of laryngopharyngeal reflux.
METHODS:
A total of 91 asymptomatic subjects were recruited in this study. Participants provided a fasting saliva specimen for pepsin measurement using enzyme-linked immunoadsorbent assay, completed the reflux symptom index (RSI) assessment and underwent laryngostroboscopic examination using a rigid endoscope. Their RFS were graded according to the laryngeal findings.
RESULTS:
The median concentration of pepsin in 91 asymptomatic volunteers was 55.5 μg/L (range 3.53-191.64 μg/L). The mean individuals RSI was 2.24±2.34, and the mean individuals RFS was 5.78±1.74.
CONCLUSIONS
Our data demonstrate that certain concentration of pepsin was detected and showed a higher RFS score in asymptomatic volunteers.
Humans
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Laryngopharyngeal Reflux
;
diagnosis
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Laryngoscopy
;
Pepsin A
;
analysis
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Saliva
;
chemistry
;
Volunteers

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