1.Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/ Wee1 Pathway
Zhengyang PAN ; Guoxi XU ; Yan ZHANG ; Meiling WU ; Jiahui YU ; Xujun HE ; Wei ZHANG ; Junfeng HU
Journal of Gastric Cancer 2024;24(3):300-315
Purpose:
Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin.
Materials and Methods:
We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1.
Results:
Our study reveals Gal-1 expression was significantly associated with poor outcomes.Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/ Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects.
Conclusions
These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.
2.Influential factors of hypoalbuminemia in patients with preeclampsia and observation of pregnancy outcomes
Cui PENG ; Qin SHE ; Huiqin HE ; Zhi CHENG ; Mulan ZENG ; Xujun HUANG
Chinese Journal of Primary Medicine and Pharmacy 2023;30(4):546-551
Objective:To analyze the influential factors of hypoalbuminemia in patients with preeclampsia and observe the pregnancy outcomes.Methods:The clinical data of 237 pregnant women with preeclampsia who received treatment in The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital) from July 2018 to December 2020 were retrospectively collected and analyzed. These patients were divided into hypoproteinemia (observation group) and no hypoproteinemia (control group) groups according to whether they had hypoproteinemia. The general situation, clinical data, and adverse maternal and infant outcomes were statistically analyzed. Risk factors of hypoalbuminemia were analyzed using a logistic regression model. The predictive efficacy was evaluated using the receiver operating characteristic curve.Results:There were no significant differences in general data between the two groups (all P > 0.05). Multivariate analysis showed that D-dimer ( OR = 1.25, P = 0.004), 24-hour urinary protein ( OR = 1.29, P < 0.001), and total bile acid ( OR = 1.08, P = 0.010) were the independent risk factors for hypoproteinemia in preeclampsia. The predictive efficacy of these three indicators (area under the receiver operating characteristic curve = 0.855, P < 0.001) was greater than that of a single indicator. The incidences of adverse maternal and infant outcomes including placental abruption (9.4%, P = 0.019), liver and kidney dysfunction (34.4%, P < 0.001), pleural and ascitic fluid (28.1%, P = 0.001), fetal intrauterine growth restriction (50.0%, P = 0.001), fundus lesions (6.2%, P = 0.018), HELLP syndrome (9.4%, P = 0.019), mild neonatal asphyxia (15.6%, P = 0.022), severe asphyxia (6.2%, P = 0.049), metabolic acidosis (12.5%, P = 0.001), intrauterine infection (12.5%, P = 0.004), and neonatal hospitalization for more than 20 days (37.5%, P < 0.001) were greater in the observation group compared with the control group. There were no significant differences in postpartum hemorrhage, eclampsia, respiratory distress syndrome, fetal loss, and neonatal death between the two groups (all P > 0.05). Conclusion:D-dimer, 24-hour urinary protein, and total bile acid are independent risk factors for hypoproteinemia in preeclampsia. Patients with preeclampsia complicated by hypoproteinemia have a high risk of adverse maternal and infant outcomes.
3.SPTLC2 gene mutation leads to intermediate Charcot-Marries-Tooth disease: a family report
Jian MENG ; Jun FU ; Kang DU ; Xujun CHU ; Lingchao MENG ; He LYU ; Zhaoxia WANG ; Yun YUAN
Chinese Journal of Neurology 2022;55(12):1353-1358
Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.
4.Associations of white matter microstructural abnormalities with clinical symptoms, cognitive impairment and clinical outcomes in the early course of first-episode schizophrenia
Shenhong WENG ; Gaohua WANG ; Shunsheng XU ; Zhongchun LIU ; Qinran ZHANG ; Xiufen ZOU ; Changchun HE ; Xujun DUAN ; Maolin HU ; Xiaofen ZONG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(11):997-1004
Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.
5.The single-cell proteomics methods based on liquid chromatography tandem mass spectrometry promote tumor diagnosis research
Yi HE ; Xujun LIANG ; Pengfei ZHANG
Chinese Journal of Laboratory Medicine 2021;44(8):755-763
Single-cell proteome analysis can perform in-depth research on cell heterogeneity and further promote the development of precision medicine and tumor research. In recent years, mass spectrometry-based proteomics has made substantial progress, but proteomics analysis at the single-cell level still faces sensitivity challenges. At present, liquid chromatography tandem mass spectrometry has become the main analysis method of proteomics. Because of its high sensitivity, high throughput, and high stability, it has been widely used in the field of single cells. In recent years, the representative single-cell proteomics methods can be divided into three types: single-tube technology, microfluidic platform, and integrated processing platform according to different sample processing methods. Different kinds of data collection and analysis methods have their own advantages and disadvantages. If single-cell proteomics, still a laboratory study, can be applied in diagnostic practice as soon as possible, it will definitely promote the progress of precision medicine and oncology research.
6.Expression of tumor-associated vascular insulin receptor in colorectal cancer and its relationship with tumor pathological features.
Zeran YANG ; Xin ZHANG ; Jie MA ; Li JIN ; Xujun HE
Journal of Zhejiang University. Medical sciences 2020;49(6):725-731
OBJECTIVE:
To study the expression of tumor associated vascular insulin receptor (TVIR) in colorectal cancer with or without metabolic syndrome (MS) and its relationship with the pathological features of colorectal cancer.
METHODS:
The expression of TVIR in 220 colorectal cancer specimens was detected by tissue microarray and immunohistochemistry. The relationships between the expression of TVIR and the pathological features (pathological subtypes, histological grade, invasion depth, lymph node metastasis and TNM stage) of colorectal cancer with/without MS were analyzed.
RESULTS:
The insulin receptor expression was observed in colorectal cancer tissue or border area between cancer and normal tissue, but not in normal intestinal tissue. The high-expression rates of TVIR in MS group was remarkably lower than that of non-MS group (21.6%vs. 41.0%,
CONCLUSIONS
s: High-expression of TVIR is associated with aggressive pathological features such as invasion, lymph node metastasis and high TNM stage of colorectal cancer, especially for those patients without MS. TVIR could be a useful biological marker for prognosis of colorectal cancer.
Biomarkers, Tumor/genetics*
;
Colorectal Neoplasms/physiopathology*
;
Gene Expression Regulation, Neoplastic
;
Humans
;
Neoplasm Staging
;
Prognosis
;
Receptor, Insulin/genetics*
7.Advantages of Restoring miR-205-3p Expression for Better Prognosis of Gastric Cancer via Prevention of Epithelial-mesenchymal Transition
Zhen ZHANG ; Xujun HE ; Ji XU ; Genhua ZHANG ; Yue YANG ; Jie MA ; Yuanshui SUN ; Haibin NI ; Fengyong WANG
Journal of Gastric Cancer 2020;20(2):212-224
Purpose:
miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion.
Materials and Methods:
Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2).
Results:
We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2.
Conclusions
miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.
8.Acute effect of air pollutants (carbon monoxide and ozone) on myocardial infarction mortality in Ningbo
Xujun QIAN ; Guoxing LI ; Tianfeng HE ; Hui LI ; Jing HUANG ; Guozhang XU ; Xinbiao GUO ; Li LI
Chinese Journal of Epidemiology 2017;38(3):297-302
Objective To explore the effect of carbon monoxide (CO) and ozone (O3) in the air on the myocardial infarction mortality in Ningbo,Zhejiang province,from 2011 to 2015.Methods The data of daily air quality surveillance and the causes of deaths in Ningbo from January 1,2011 to December 31,2015 were collected and the time series study using a generalized additive model was conducted to evaluate the relationship between the mortality of myocardial infarction and the air pollutants after adjustment for the long-term trend of death,weather conditions,"days of the week" and other confounding factors.Results The daily average concentrations of CO and O3 in Ningbo during 2011-2015 were 0.90 (0.02-3.31) mg/m3 and 82.78 (4-236) μg/m3,respectively.A total of 5 388 myocardial infarction deaths occurred,with a daily average of 3 deaths.In single-pollutant model,an increase of 0.1 mg/m3 in average concentration of CO could increase the risk of myocardial infarction mortality by 1.06% (95% CI:0.29%-1.93%) in general population,and by 1.26% (95% CI:0.28%-2.24%) in aged people aged ≥65 years in lagged 6 days,but the influence was not significant in people aged <65 years.The influence had no significant difference in males,but it increased the risk of myocardial infarction mortality by 1.77% in females (95% CI:0.44%-3.13%).In multipollutant model,CO did remain robust after adjusting for other co-pollutants.Whereas the effect of O3 had no significant influence.Conclusion These findings suggested that the increased risk of daily myocardial infarction mortality was associated with the increase of CO concentration,but no such association was found for O3 in Ningbo.
9.Relationship between particulate matters and cardio-cerebrovascular mortality in Ningbo: a time-series study
Xujun QIAN ; Yueping SHEN ; Tianfeng HE ; Guozhang XU ; Shaohua GU
Chinese Journal of Epidemiology 2016;37(6):841-845
Objective To explore the short-term effect of particulate matters with an aerodynamic diameter of less than or equal to 10 μg (PM10) and aerodynamic diameter of less than or equal to 2.5 μg (PM2.5) on cardio-cerebrovascular mortality in Ningbo city.Methods Daily cardiocerebrovascular mortality data from 2011 to 2014 in Ningbo city were collected and the time series study using a semi-parametric generalized additive model were used to evaluate the relationship between the mortality of cardio-cerebrovascular disease and particulate matters after adjustment for the long-term trend of death,weather conditions,"days of the week" and other confounding factors.Results In single-pollutant model,the short-term effects of particulate matter on cardio-cerebrovascular mortality was strongest in lagged 2 days in Ningbo city,and an increase of 10 μg/m3 in moving average concentrations (lagged 2-3 days and lagged 2-4 days) of PM2.5 and PM10 could increase the cardio-cerebrovascular mortality by 0.55% (0.23%-0.87%) and 0.53% (0.28%-0.78%),respectively.In multi-pollutant models,PM10 did remain robust after being adjusted for PM2.5 with 0.58% (0.09%-1.07%) increase in cardio-cerebrovascular mortality.The effect of PM2.5 had no statistical significantce after being adjusted for other co-pollutants.Conclusion These findings suggested that the concentrations of ambient particulate matters were associated with an increased risk of daily cardio-cerebrovascular mortality in Ningbo city.
10.Expression of NEK-6 in gastric cancer and its clinical significance.
Ji XU ; Qiwen HE ; Xujun HE ; Qinshu SHAO ; Houquan TAO ; Zaiyuan YE
Chinese Journal of Gastrointestinal Surgery 2015;18(10):1036-1040
OBJECTIVETo explore the NEK-6 expression in gastric cancer tissue and its relationship with clinicopathological features.
METHODSFluorescent quantification PCR and Western blotting were used to examine the NEK-6 expression in 36 samples of fresh gastric cancer tissues and para-cancer gastric mucosal tissues, human gastric cancer cell lines(BGC-823, MKN-28, SGC-7901, MGC-803, HGC-27, AGS), and human normal gastric epithelial cell line (GES-1). Gastric cancer cell lines with the highest expression level were selected to perform the invasion and migration tests, and the effect of down-regulated NEK-6 expression by siRNA transfection on above invasion and migration tests were observed. Meanwhile NEK-6 expression in 94 paraffin samples of gastric cancer tissues was examined by immunohistochemistry and its positivity was compared among different clinicopathologic features.
RESULTSFluorescent quantification PCR revealed gastric cancer tissues had significantly higher NEK-6 expression than para-cancer tissues(0.002 80±0.001 36 vs. 0.001 91±0.001 48, P<0.05), NEK-6 expression was up-regulated in 31 gastric cancer tissues (86.1%), and human gastric cancer cell lines had significantly higher NEK-6 expression than GES-1 cells, among whom BGC-823 and AGS cell lines were the highest. Invasion and migration tests showed that as compared to negative siRNA control group, ability of invasion and migration in BGC-823 and AGS cells after siRNA transfection was obviously decreased. In 94 paraffin samples, positive expression rate of NEK-6 was 60.6%(57/94), and NEK-6 expression was significantly associated with gastric cancer distant metastasis, lymph nodes metastasis and TNM staging(all P<0.05).
CONCLUSIONSNEK-6 expression is up-regulated in gastric cancer tissues, which is significantly associated with distant metastasis, lymph nodes metastasis and TNM staging. Down-regulation of NEK-6 expression can inhibit the ability of invasion and migration in gastric cancer cells.

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