ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.

Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.

Objective:To investigate the effect of single nucleotide polymorphism (SNP) of FCN gene on the susceptibility of pre-eclampsia (PE) in Han nationality pregnant women.Methods:A total of 274 PE pregnant women (PE group) and 154 healthy pregnant women (control group) admitted to Boai Hospital of Zhongshan, Affiliated Hospital to Southern Medical University from October 2020 to October 2022 were collected. The general information, medical history, reproductive history, blood pressure, body mass index and blood biochemical indicators before delivery were compared between the two groups. Twenty-three SNP loci of FCN gene family were genotyped by time-of-flight mass spectrometry, and the serum levels of ficolins (ficolin-1, -2 and -3) were detected by enzyme-linked immunosorbent assay.Results:(1) Compared with the control group, the body mass index, mean arterial pressure, gestational age at delivery, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, direct bilirubin, albumin, and C-reactive protein in the PE group were significantly higher than those in the control group (all P<0.05). The levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), placental growth factor (PlGF) and human soluble vascular endothelial growth factor receptor-1 (sFlt-1) were significantly different between the two groups (all P<0.05). (2) Among the 23 SNP loci in FCN gene family, 18 loci were in Hardy-Weinberg genetic equilibrium, including 5 loci in FCN1 gene, 10 loci in FCN2 gene, and 3 loci in FCN3 gene. Five loci that did not conform to Hardy-Weinberg genetic equilibrium were not included in the subsequent analysis. Compared with the control group, the genotype distribution of 3 loci of FCN2 gene (rs7872508, rs11103563, rs73664188) and 1 locus of FCN3 gene (rs3813800) in the PE group were significantly different (all P<0.05). After Bonferroni correction, only the genotype distribution of rs7872508 and rs73664188 in FCN2 gene were statistically different between the PE group and the control group (all P<0.05). Further analysis showed that for the rs7872508 locus of FCN2 gene, compared with GG genotype, genotype GT ( OR=3.025, 95% CI: 1.080-8.471) and TT ( OR=4.777, 95% CI: 1.758-12.979) both significantly increased the risk of PE (both P<0.05). For rs73664188 locus of FCN2 gene, compared with TT genotype, genotype TC ( OR=0.510, 95% CI: 0.334-0.778) significantly reduced the risk of PE ( P<0.05). (3) Compared with the control group, the serum levels of ficolin-1 and ficolin-2 in pregnant women in the PE group were significantly reduced (both P<0.05), while the level of ficolin-3 showed no significant change ( P=0.271). Correlation analysis showed that the serum levels of ficolin-2 in pregnant women in the PE group were significantly positively correlated with PlGF level ( r=0.321, P<0.001), and significantly negatively correlated with sFlt-1 level ( r=-0.187, P=0.002) and NT-proBNP level ( r=-0.392, P<0.001). Further analysis revealed that the serum levels of ficolin-2 in pregnant women of the PE group with GT and TT genotypes at rs7872508 locus of FCN2 gene were significantly reduced (both P<0.05), while the serum level of ficolin-2 in pregnant women of the PE group with TC genotype at the rs73664188 locus were significantly increased ( P<0.05). Conclusion:The SNP of FCN2 gene in FCN gene family might be related to the susceptibility to PE and have an effect on serum ficolin-2 level in PE pregnant women.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.