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    20 October 2023, Volume 44 Issue 5
    Research progresses in  cerebral venous sinus thrombosis animal models
    Ma Wei, Zhou Yifan, Jiang Huimin, Wei Huimin, Zhou Chen, Ji Xunming
    2023, 44(5):  704-714.  doi:10.3969/j.issn.1006-7795.2023.05.002
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    Cerebral venous sinus thrombosis (CVST) is a special subtype for 0.5%-1% of all strokes,and it tends to occur in young adults and women. It is a difficult disease in neurology because of its complex pathology. The clinical diagnosis is difficult, with high rate of missed diagnosis and misdiagnosis, and severe mortality rate up to 30%. Beyond thrombosis, different CVST-related parenchymal injuries may occur and include edema, ischemic strokes, and intra-cerebral hemorrhage. There are many uncontrollable factors  involved during CVST development. In order to further explore the pathological evolution and molecular pathological characteristics of CVST, it is necessary to establish a suitable animal model of CVST to study the molecular pathological mechanisms of CVST thrombosis, brain tissue damage and related prevention and treatment programs. Importantly, animal models are useful to study new therapeutic approaches. In this review, we provide a mainly overview of CVST experimental animal models, focusing on their strengths, limits, and applications for relevant studies.
    Recent study advances and reviews in basic pharmacology and related fields
    Luo Dali, Qu Xianjun, Jiang Mengxi, Jin Zengliang, Fan Zheng, Xue Ming
    2023, 44(5):  715-723.  doi:10.3969/j.issn.1006-7795.2023.05.003
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    In recent years, the basic pharmacological research is shifting from the strategies of new drug development and rational drug use-oriented research to innovation-driven and multi-target and molecular action mechanism-oriented in-depth systematic research. In this article, we summarized and reviewed the research progress in some fields of basic pharmacology in China, and make a prospect to further development for the basic pharmacology research.
    Bioinformatics analysis of hippocalcin like 1 expression and clinical prognosis in primary central nervous system lymphoma
    Yu Jianyu, Zheng Yi, Li Wenbin
    2023, 44(5):  724-732.  doi:10.3969/j.issn.1006-7795.2023.05.004
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    Objective  To infer the role of HPCAL1 in primary central nervous system lymphoma (PCNSL) based on bioinformatics analysis of the expression level and clinical significance of hippocalcin like 1 (HPCAL1) in PCNSL. Methods  The expression data and clinical information of 7 PCNSL tissues and 7 normal brain tissues were downloaded from the GSE25297 dataset in the Gene Expression Omnibus (GEO) database to plot the receiver operating characteristic  (ROC) curve of diagnostic value of HPCAL1 expression level. The expression data and clinical information of 34 PCNSL patients were downloaded from the GSE34771 dataset, and divided into two groups with high and low expression according to the median HPCAL1 expression level, and the survival curves of the high and low expression groups, the multivariate prognostic analysis of HPCAL1 expression and clinical information, the volcano map and heat map of differentially expressed genes in the high-low expression group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes, and the protein interaction network (PPI) analysis of the first 20 up-regulated and down-regulated differentially expressed genes were mapped. Results  The expression of HPCAL1 is an independent prognostic factor and can be used as a basis for whether there is a disease or not. Compared with the HPCAL1 low-expression group, the high-expression group showed a longer overall survival. Through GO analysis, differential genes mainly focus on molecular functions such as maintaining cell homeostasis, promoting cell differentiation, inhibiting cell infinite proliferation and migration, and inhibiting transmission of nerve synapses. According to KEGG pathway analysis, differential genes were mainly concentrated in immune-related pathways such as cytokine-cytokine receptor interaction, lysosome, phagosome, and inflammation, and functional pathways such as Rap1 signaling pathway, extracellular matrix receptor interaction, and metabolic pathway. Conclusions  Compared with the HPCAL1 low-expression group, the high-expression group showed a better prognosis. According to the expression level of HPCAL1, PCNSL patients can be intervened, and it is necessary to use HPCAL1 gene as a candidate biomarker for PCNSL. 
    Construction and application of the human glioblastoma cell line Y1203
    Zheng Yi, Song Lairong, Xu Xiaoying, Wu Zhen, Li Xiaojie, Xie Lei, Chen Feng, Li Wenbin
    2023, 44(5):  733-740.  doi:10.3969/j.issn.1006-7795.2023.05.005
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    Objective  To establish a glioblastoma cell line, Y1203, with stem cell-like phenotypes for the study of tumor cell stemness maintenance and potential mechanisms of treatment resistance. Methods  Y1203 cells were derived from tumor tissue obtained by recurrent resection in a 49-year-old female glioblastoma patient. Y1203 cells were used to establish patient-derived tumor xenograft (PDX) models both orthotopically and subcutaneously. Flow cytometry was applied to analyze the cell cycle distribution of different passages of Y1203 cells. Real-time quantitative polymerase chain reaction was performed to assess the expression of stem cell markers, including transcription factor SOX-2 (SOX2) and cluster of differentiation-44 (CD44). RNA-Seq was conducted to compare the expression profiles between Y1203 and U87 cells. Results  The short tandem repeats (STR) analysis confirmed the homogeneity between Y1203 cells and the patient’s tumor tissue, and they were distinct from commonly used cell lines available in the ExPASy database. Genetic testing revealed isocitrate dehydrogenase 1 (IDH1) wild-type, telomerase reverse transcriptase (TERT) promoter mutation, B-Raf proto-oncogene (BRAF V600E) mutation, tumor protein p53 (TP53) mutation, and ATRX chromatin remodeler (ATRX) mutation. The human glioblastoma cell line Y1203 exhibited unlimited proliferation in vitro and thus orthotopic and subcutaneous glioblastoma models was successfully established. Compared to other glioma cell lines, Y1203 cells showed high expression of the tumor stem cell markers CD44 and SOX2, as well as significant enrichment of glioma stem cell-associated pathways. Conclusions  The human glioblastoma cell line Y1203 shows low differentiation, high malignancy, and strong resistance to radiotherapy and chemotherapy, and it possesses glioblastoma stem cell characteristics. The establishment of Y1203 cell line provides an experimental basis for preclinical studies of glioblastoma.
    Preliminary study on the effect of UNC0379 on the proliferation of glioma cells
    Liu Xiu, Li Wencai
    2023, 44(5):  741-746.  doi:10.3969/j.issn.1006-7795.2023.05.006
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    Objective To explore the effect and mechanism of UNC0379, an inhibitor of lysine methyltransferase 5A (KMT5A), on the proliferation of glioma cells. Methods LN229 cells were treated with UNC0379, then cell proliferation was detected by Cell counting kit-8 (CCK8), and cell apoptosis and cell cycle were measured by flow cytometry. Multi-drug combination response was also analyzed to evaluate the impact of UNC0379 on temozolomide efficacy in glioma cells. Results UNC0379 inhibited the proliferation of LN229 cells effectively (P<0.05). Although UNC0379 didn’t induce apoptosis in LN229 cells, the percentage of G2/M cells increased. UNC0379 also promoted the efficacy of temozolomide in LN229 cells. Conclusion UNC0379 could inhibit the proliferation of glioma cells by inducing cell cycle arrest and could also enhance temozolomide efficacy.
    Study of genes associated with aberrant methylation regulation in high-grade meningiomas
    Peng Yichen, Zheng Yi, Li Shenglan, Yu Jianyu, Lan Yanjie, Liu Xinrui, Chen Feng, Li Wenbin
    2023, 44(5):  747-752.  doi:10.3969/j.issn.1006-7795.2023.05.007
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    Objective To explore potential therapeutic targets with bioinformatics for the treatment of meningiomas, the most common primary central nervous system tumors. Methods A preliminary understanding of the genomic characteristics of high-grade meningiomas was obtained through analysis of public databases to assess the genes associated with aberrant methylation regulation. Results A total of 3 006 genes whose expression was regulated by aberrant methylation were identified, including 210 genes with high mutation frequency, and pathways associated with malignant tumor development and migration were mined. Conclusions Genes and related pathways potentially regulated by aberrant methylation in high-grade meningioma provides bio-markers and potential therapeutic targets for high-grade meningioma.
    Major tobacco carcinogen benzo(a)pyrene induces infiltration of M2 type macrophages by upregulating cyclooxygenase-2 expression in esophageal squamous carcinoma
    Xiao Zeru, Yan Rui, Liang Ziwei, Ge Yang, An Guangyu
    2023, 44(5):  753-761.  doi:10.3969/j.issn.1006-7795.2023.05.008
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    Objective  To investigate the potential mechanism of increased infiltration of M2 tumor-associated macrophages in the tumor microenvironment of esophageal squamous carcinoma patients with a history of smoking. Methods Differential expression of M2 tumor-associated macrophages in esophageal squamous carcinoma patients with/without a history of smoking was examined by immunohistochemistry and CIBERSORT database analysis. The expression of cyclooxygenase-2(COX2)involved in the regulation of macrophage recruitment and polarization was detected in tumor tissues of esophageal squamous cell carcinoma(ESCC)patients with a history of smoking by The Cancer Genome Atlas (TCGA)database. Esophageal squamous carcinoma cell lines were treated with benzo(a)pyrene, the major carcinogen in tobacco. Changes in the expression of COX2 of ESCC cell lines were detected by Western blotting and real time quantitative PCR (RT-qPCR). The effect on macrophage recruitment by tumor cell conditional medium was assessed by Transwell assay before and after benzo(a)pyrene stimulation. A co-culture system of tumor cell conditional medium and macrophage was established. Western blotting and RT-qPCR were used to evaluate the expression changes of M2 tumor associated macrophages (TAM)markers. Macrophage morphological changes were observed to assist in determining their polarization. Results  The infiltration of M2 macrophages was significantly increased in patients with a history of smoking. COX2 was significantly increased in esophageal squamous carcinoma cells stimulated by benzo(a)pyrene, the major carcinogen in tobacco. The recruitment of macrophages by tumor cell conditional medium was significantly increased after stimulation with benzo(a)pyrene. The treatment of macrophages with tumor cell conditional medium after stimulation with benzo(a)pyrene induced their polarization towards M2 macrophages. Conclusions  Stimulation of esophageal squamous carcinoma cell lines with benzo(a)pyrene induces macrophages to enter the tumor microenvironment and induces polarization towards M2 tumor-associated macrophages.
    The mechanism of miR-150 targeted regulation of IGF2BP2 on the malignant phenotype of liver cancer
    Tan Yubo, Suboyinuer Tuerhong, Huang Jing, Zhang Tingting, Liu Junjie, Shaya Mahati
    2023, 44(5):  762-767.  doi:10.3969/j.issn.1006-7795.2023.05.009
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    Objective  To elucidate the impacts and targets of miR-150 in hepatocellular carcinoma (HCC). Methods  Heatmap analysis was utilized for screening the differentially expressed miRNAs between six sets of HCC tissues and adjacent liver tissues downloaded from The Cancer Genome Atlas database. Quantitative real-time polymerase chain reaction was employed for assessing miR-150 expression in HCC tissues and cell lines. Then, cell counting Kit-8 assay and Transwell assay separately were conducted to evaluate the proliferation, invasion and migration potential of HCC cells. Besides, TargetScan software was utilized for predicting the potential targets of miR-150. Moreover, the relationship between miR-150 and its target genes were determined by Western blotting and luciferase reporter assay. Results  We identified 31 deregulated miRNAs (including the most significantly down-regulated miR-150) in HCC tissues. MiR-150 expression was significantly reduced in HCC tissues and cell lines. Highly expressed miR-150 significantly increased the 5-year survival rate of HCC patients. Meanwhile, miR-150 induced a significant reduction of the cell proliferation, migration, and invasion potentials of human hepatocarcinoma cells (SMMC-7721and HepG2). We found miR-150 directly target recombinant insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) and decrease human phosphorylation phosphotylinosital 3-kinase and protein kinase B signal (p-PI3K/Akt) pathway. Conclusions  These results suggested that miR-150 restrained proliferation, migration, and invasion of HCC cells by regulating IGF2BP2, providing a new therapeutic target for HCC.
    Progresses on the mutation of SWI/SNF complex and its impact on immune checkpoint inhibitor therapy response in hepatocellular carcinoma
    Yin Xue, Yu Minghang, Wang Xi, Chen Jinglong
    2023, 44(5):  768-774.  doi:10.3969/j.issn.1006-7795.2023.05.010
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    The SWI/SNF (SWItch/sucrose non-fermentable) complex is an ATP-dependent chromatin remodeling complex, and its subunits are frequently mutated or lost in hepatocellular carcinoma (HCC). These mutations or losses can lead to abnormal chromatin structure and function, thus affecting the biological behavior of HCC cells and influencing the response to immune checkpoint inhibitors(ICIs)therapy in HCC patients. This review primarily summarizes the research progresses on the subunit mutations of the SWI/SNF complex in HCC and their association with ICIs therapy response. It explores the relationship between subunit mutations, ICIs therapy response rate, drug resistance, and predictive biomarkers, as well as provides insights into future research directions and the clinical application prospects.
    Novel drug therapies promote the treatment progress of primary central nervous system lymphoma
    Yin Shuo, Chen Feng, Zheng Xiaohong, Zhang Weichunbai, Li Wenbin
    2023, 44(5):  775-781.  doi:10.3969/j.issn.1006-7795.2023.05.011
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    Primary central nervous system lymphoma is a rare and highly aggressive extranodal non-Hodgkin lymphoma. Up to date, there is no optimal treatment strategy. Currently, high-dose methotrexate-based chemotherapy serves as the first-line approach. Despite achieving some efficacy in disease control, its toxic side effects and limitations cannot be overlooked. With deeper molecular research in  this disease, the significant breakthroughs in novel drug therapies like targeted treatment and immunotherapy have achieved. The exploration of combinations between different drug therapies has expanded the horizons of related treatments, propelling advancements in the treatment of primary central nervous system lymphoma.
    Erythrocytic alpha-synuclein in early-onset Parkinsons disease and the clinical application
    Liu Genliang, Yu Zhenwei, Feng Tao
    2023, 44(5):  782-787.  doi:10.3969/j.issn.1006-7795.2023.05.012
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    Objective To investigate whether α-synuclein levels in peripheral erythrocytes are associated with early-onset Parkinson‘s disease(PD). Methods The subjects included 47 patients with early-onset PD and 52 healthy controls.The venous blood was obtained to separate erythrocyte.  The electrochemiluminescence assay was used to measure total and oligomeric α-synuclein levels. After 2 year  25 PD patients were re-examined with repeated blood collection and clinical assessments. Results Compared with control group total and oligomeric α-synuclein levels in erythrocyte  in early-onset PD groups were significantly increased[total α-synuclein: 1.28(0.94, 2.13) vs  0.57(0.41, 0.70), P<0.001; oligomer: 202.18(152.16, 244.22) vs 128.40(107.61, 157.02), P<0.001]. In the follow-up study over 2 years, motor and cognitive scores did not process after 2-year follow-up,   but erythrocytic oligomeric α-synuclein levels in early-onset PD  were significantly increased than that at baseline [211.66(159.71, 263.73) vs 170.12(139.31, 233.42), P=0.046]. Conclusion Our study suggests that total and oligomeric α-synuclein in erythrocyte were elevated in early-onset PD and could serve as a potential diagnostic biomarker for PD and could serve as a potential diagnostic biomarker for PD.
    Cognitive function and risk factors in patients with chronic kidney disease
    Feng Yiduo, Huang Qi, Zhou Yilun
    2023, 44(5):  788-794.  doi:10.3969/j.issn.1006-7795.2023.05.013
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    Objective  To evaluate cognitive function and potential risk factors in patients with chronic kidney disease (CKD). Methods  Totally 132 patients from Beijing Tiantan Hospital, Capital Medical University were included in this study, and they were divided into four groups according to CKD criteria and estimated glomerular filtration rate (eGFR) levels: healthy participants (n=25), mild CKD [(eGFR ≥ 60 mL·min-1·(1.73 m2)-1] group  (n=51), moderate to severe CKD [eGFR<60 mL·min-1·(1.73 m2)-1] group  (n=34), and CKD hemodialysis group (n=22).  The participants had a median eGFR of 94.0  mL·min-1·(1.73 m2)-1, with an average age of (55.3 ± 14.0) years. Clinical characteristics of the patients were compared between 4 groups. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA). Furthermore, sleep breathing monitoring was performed on the included participants, including sleep apnea Hypopnea index (AHI) and oxygen reduction index (ODI), The statistical analysis was done with morpheus ox software. Analysis of variance and Chi-squared test were used to compare differences between groups. The correlation and cognitive-related risk factors were determined by logistic regression analysis. Results  Compared with healthy control group, MoCA scores decreased with renal function deterioration, and the impairment of executive function was more severe (P<0.01). The multivariate logistic regression analysis results suggested that low hemoglobin (OR=0.97, 95% CI: 0.95-0.99) and age (OR=1.10, 95% CI: 1.05-1.15) might be risk factors for cognitive impairment in CKD patients. Conclusions  CKD patients might show cognitive impairment with a decrease of eGFR levels, and clinical symptoms could be more severe in these patients.  Low hemoglobin and age may be risk factors accounting for cognitive impairment in CKD patients.
    A clinical study on stroke prevention in patients with non-valvular atrial fibrillation at high bleeding risk by standalone left atrial appendage closure under total thoracoscopy
    Yang Yu, Ye Cong, Yang Chengzhi, Xu Dong
    2023, 44(5):  795-802.  doi:10.3969/j.issn.1006-7795.2023.05.014
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    Objective  To explore the efficacy and safety of standalone left atrial appendage closure under total thoracoscopy on stroke prevention in patients with non-valvular atrial fibrillation at high bleeding risks. Methods  A total of 66 patients with non-valvular atrial fibrillation at high risk of bleeding were enrolled, including 7 patients with paroxysmal atrial fibrillation, and 59 patients with persistent or permanent atrial fibrillation.  The efficacy of standalone left atrial appendage closure under total thoracoscopy was evaluated in patients with non-valvular atrial fibrillation at high bleeding risks. Furthermore, adverse events associated with operation were recorded to demonstrate the protective effect on stroke during follow-up. Results  The left atrial appendage were successfully closed in all the participants, with an average duration of (2.22±0.97) hours. About 90% of patients showed residual roots no more than 10 mm after surgery, and all patients had no internal leakage or displacement of the auricle clip. No significant differences in surgery time, postoperative drainage, and surgical success rate were observed between elderly patients and comparators. One should be noted that elderly patients showed a longer postoperative extubation time compared to other age groups, while all patients were successfully extubated. No unplanned secondary surgeries were performed, accompanied with no perioperative deaths based on safety parameters. Bleeding event was reported in one patient, which was attributed to the pull of the auricle tip during surgery. Bleeding event was efficiently ceased after releasing the auricle clip. An average follow-up lasted (17.3±0.7) months. Two patients developed new onset of ischemic stroke, with one presenting with new cerebral infarction and the other presenting with transient ischemic attack. Conclusions  The standalone left atrial appendage closure under total thoracoscopy serves as a novel treatment option for stroke prevention in patients with non-valvular atrial fibrillation at high bleeding risks. This procedure is characterized with high success rate, low incidence of leaks and fewer complications. Furthermore, similar efficacy and safety were observed in elderly patients undergoing surgery compared to the control group matched with other factors.
    Research progress on non-pharmacological therapy of freezing of gait in Parkinson’s disease
    Huo Yuan, Qu Yan, Li Xiaohong
    2023, 44(5):  803-810.  doi:10.3969/j.issn.1006-7795.2023.05.015
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    Parkinson's disease (PD) is a common neurodegenerative disease, in the late stage of which freezing of gait (FOG) is a kind of movement symptom in the late stage of PD that can cause disability, and seriously affects the quality of life of patients.The treatment of FOG mainly includes pharmacological therapy and non-pharmacological therapy.Currently,pharmacological therapy has limited efficacy for FOG.Therefore,  a variety of non-pharmacological therapy have been applied to treat FOG, including surgery,noninvasive neuromodulation,compensation therapy, and rehabilitation training,etc. This systematic review summarizes the research progress in non-pharmacological therapy of FOG in the recent years.
    Transcriptome sequencing and survival analysis of noncirrhotic hepatitis B viral(HBV)-related hepatocellular carcinoma
    Wan Yan, Liu Fang, Guo Shan, Wu Jian
    2023, 44(5):  811-820.  doi:10.3969/j.issn.1006-7795.2023.05.016
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    Objective  Transcriptome sequencing and bioinformatics analysis were used to explore the transcriptional characteristics and survival analysis of non-cirrhotic hepatitis B viral(HBV)-related hepatocellular carcinoma (HCC). Methods  The differentially expressed genes in non-cirrhotic HBV-related HCC were obtained by transcriptome sequencing. The biological functional processes and signaling pathways involved in the differentially expressed genes were obtained by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key genes were obtained by gene-gene function interaction network analysis, and the key genes were analyzed for survival prognosis using the cancer genome atlas (TCGA) database’s HCC cohort. Results  A total of 3 672 up-regulated differential genes and 2 715 down-regulated differential genes were identified. The GO functional enrichment analysis mainly involved cell differentiation, DNA replication, DNA repair, inflammation response, immune response, cell adhesion, etc, while the KEGG pathway enrichment mainly included cell cycle, oxidative phosphorylation, p53 signaling pathway,tumor necrosis factor(TNF) signaling pathway, and nuclear factor kappa-B(NF-κB) signaling pathway. Among them, high expression of mitogen-activated protein kinase 3(MAPK3), ras-related C3 cotulinum toxin substrate 1(RAC1),phospholipase C beta 1(PLCβ1), catenin beta 1(CTNNβ1), non-metastatic cells 1(NME1), and non-metastatic cells 6(NME6) was associated with poor prognosis in HCC patients (P<0.05), while low expression of FYN, cytochrome P450 2C8(CYP2C8), and cytochrome P450 2C9(CYP2C9) was associated with poor prognosis in HCC patients (P<0.05). Conclusions  Non-cirrhotic HBV-related HCC involves multiple biological processes and alterations in signaling pathways, and the key genes related to the survival and prognosis of HCC patients provide new clues for understanding the mechanism of HBV-related HCC in non-cirrhosis patients.
    The effect of lncRNA FAM95B1 on the pathogenesis of intrauterine adhesion by regulating insulin-like growth factor 2
    Wu Jianhong, Tian Yucui, Jiang Ziwen, Tang Shiqian, Liu Zhaohui, Dai Yinmei
    2023, 44(5):  821-827.  doi:10.3969/j.issn.1006-7795.2023.05.017
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    Objective To investigate the effect of long non-coding RNA (lncRNA) family with sequence similarity 95 member B1(FAM95B1) and insulin-like growth factor 2 (IGF2) on the pathogenesis of intrauterine adhesion. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression levels of lncRNA FAM95B1, Western blotting was used to determine the protein expression levels of IGF2, α-smooth muscle actin (α-SMA) and collagen type I alpha 1 chain protein (COL1A1) in samples of intrauterine adhesion (IUA) tissue. RT-qPCR was used to determine the mRNA expression levels of lncRNA FAM95B1, IGF2, fibrotic markers (α-SMA, COL1A1, Snail ) and epithelial marker E-cadherin in endometrial stromal cells (ESCs) that had been treated with transforming growth factor-β1 (TGF-β1). Then, lncRNA FAM95B1 and IGF2 genes were down-regulated respectively to verify the regulatory relationship between lncRNA FAM95B1 and IGF2; Co-immunoprecipitation assay was performed to measure the binding relationship between lncRNA FAM95B1 and IGF2. Next, ESCs were transfected with si-FAM95B1 and then were treated with TGF-β1 to investigate the effect of lncRNA FAM95B1 and IGF2 on the transdifferentiation of ESCs into myofibroblasts. Results The expression levels of lncRNA FAM95B1, IGF2, α-SMA and COL1A1 was upregulated in IUA tissues. The mRNA expression levels of lncRNA FAM95B1, IGF2, α-SMA, COL1A1 and Snail were upregulated and the mRNA level of E-cadherin was downregulated in ESCs that had been treated with TGF-β1. IGF2 was positively regulated by lncRNA FAM95B1. LncRNA FAM95B1 and IGF2 were directly bound in TGF-β1-treated ESCs. During the epithelial-to-mesenchymal transition(EMT) of ESCs transdifferentiating into myofibroblasts, si-FAM95B1 exerted antifibrotic effect by down-regulating IGF2. Conclusions si-FAM95B1 inhibits the pathogenesis of IUA by down-regulating IGF2. LncRNA FAM95B1/IGF2 axis may provide novel molecular target for the prevention and treatment of IUA.
    Association between dietary protein intake in the first trimester and the risk of gestational diabetes mellitus in pregnant women in Beijing
    Ma Kaiwen, Zheng Wei, Zhang Puyang, Xu Lili, Li Guanghui
    2023, 44(5):  828-835.  doi:10.3969/j.issn.1006-7795.2023.05.018
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    Objective  To evaluate the dietary protein intake of pregnant women in Beijing area and explore the relationship between the intake frequency of dietary protein in the first trimester and gestational diabetes mellitus (GDM). Methods  A retrospective study was conducted on the data involving 10 320 healthy singleton pregnant women from the Beijing Birth Cohort Study. All participants visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University within 6-16 weeks of gestation from September 2018 to December 2020. Food frequency questionnaire (FFQ) was used to collect their dietary protein intake information in the first trimester. The 75g oral glucose tolerance test (OGTT) was conducted at 24 to 28 weeks of gestation, and GDM was diagnosed according to the criteria of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG). The Chi-square test or ANOVA was used to analyze the relationship between general information and the incidence of GDM. Multivariable Logistic regression analysis was used to investigate the relationship between the intake frequency of dietary protein and GDM. Results  ①Totally 15.4% (1 585/10 320) women were diagnosed with GDM in this study. ②The univariate analysis showed that the intake frequencies of total dietary protein, animal protein and red meat were associated with the incidence of GDM (P<0.05), the higher intake frequencies of them, the higher incidence of GDM; However, the intake frequencies of plant protein and white meat did not (P>0.05). Among the red meat category, the higher intake frequencies of pork, the higher incidence of GDM (P<0.05). ③The multivariate Logistic regression analysis showed that after adjusting for confounding factors such as maternal age, level of education, parity, pre-pregnancy body mass index (BMI) and family history of diabetes, the increased intake frequencies of total dietary protein in the first pregnancy increased the risk of GDM (OR=1.504, 95% CI: 1.138-1.988, P <0.05). Among them, the intake frequencies of animal protein were associated with the incidence of GDM (OR=1.429. 95% CI: 1.122-1.984, P <0.05), whereas the intake frequencies of plant protein were not. Further, the increased intake frequencies of red meat increased the risk of GDM (OR=1.288, 95% CI:1.072-1.547, P<0.05), while no differences in the occurrence of GDM were noted between women with the different intake frequencies of white meat. Among the red meat category, the increased intake frequencies of pork increased the risk of GDM (OR=1.025, 95%CI: 1.007-1.044, P<0.05). Conclusions  The main source of dietary protein for Beijing pregnant women in the first trimester was animal protein, and the main source of meat was red meat. The increased intake frequencies of animal protein, especially for red meat and pork, were risk factors of GDM incidence, while the intake frequencies of white meat and plant protein were not associated with GDM incidence. Health education and guidance should be promoted early in pregnancy, even before pregnancy, for primary prevention of GDM incidence. 
    linical comparative study of robot-assisted and fluoroscopy-assisted free-hand cortical bone trajectory screw placement in the treatment of single-level degenerative lumbar diseases
    Zhang Xinuo, Liu Yuzeng, Li Yue, Su Qingjun, Li Dongyue, Guan Li, Hai yong
    2023, 44(5):  836-844.  doi:10.3969/j.issn.1006-7795.2023.05.019
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    Objective  To compare the safety and accuracy of robotic-assisted and free-hand cortical screw placement in spinal internal fixation. Methods  A total of 71 patients who underwent cortical bone trajectory screw (CBT) for single-level degenerative lumbar spine disease at our center from December 2019 to June 2021 were retrospectively analyzed. Patients receiving fluoroscopy-assisted free-hand CBT screw placement were assigned to the free-hand group (FG, n=35) and robot-assisted CBT screw placement was assigned to the robot-assisted group (RG, n=36). Screw placement accuracy and facet violation were assessed by three-dimensional reconstruction of postoperative computed  tomography(CT). The average screw placement time, intraoperative blood loss, and intraoperative radiation exposure of medical staff were compared between the two groups.Results  A total of 284 CBT screws were implanted in 71 patients, 140 of which were completed by the FG and 144 screws by the RG. Robot-assisted nailing was significantly more accurate than free-hand nailing (92.36% vs 82.86%, P=0.015). The incidence of facet joint violation was significantly lower in the RG than in the FG (22.22% vs 40.00%, P=0.022). However, the single screw placement time was significantly longer in the RG than in the FG [(501.92±70.08) s vs (382.54±63.21) s, P=0.000]. The radiation exposure time of medical staff during surgery was significantly lower in the RG than in the FG [(56.81±16.09) s vs (34.43±16.91) s, P=0.000].Conclusions  Robot-assisted CBT screw implantation can effectively improve the accuracy of screw placement and reduce the invasion rate of superior facet and radiation exposure of medical staff, but it will increase the screw placement time and operation time of screws. Our center achieved a smooth learning curve after approximately 12 procedures.
    Clinical efficacy analysis of picosecond laser combined with traditional Chinese medicine mask in the treatment of melasma
    Shang Shuai, Liang Surong, Zhang Wensi, Tan Ansheng, Mei Xueling
    2023, 44(5):  845-851.  doi:10.3969/j.issn.1006-7795.2023.05.020
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    Objective  To analyze the efficacy and safety of 755 nm picosecond laser combined with traditional Chinese medicine mask in the treatment of melasma.Methods  Adult female patients with melasma were recruited prospectively and randomly divided into observation group and control group. The observation group received one picosecond laser treatment every 4 weeks, three times at 0, 4 and 8 week, and applied the self-made Chinese medicine facial mask twice a week for 12 weeks. The control group received only three picosecond laser treatments. The score statistics of modified Melasma Area and Severity Index (mMASI) were performed before the first laser treatment (0 week), the second laser treatment (4 week), the last laser treatment (8 week), the fourth week after the last laser treatment (12 week), the eighth week after the last laser treatment (16 week), and the twelfth week after the last laser treatment (20 week). At 12 week, the Physician Global Assessment (PGA) score, effective rate and patient satisfaction were evaluated, and adverse reactions were recorded during treatment.Results  A total of 40 patients were included, including 20 patients in the observation group and 20 patients in the control group. Totally 17 patients in the observation group and 20 patients in the control group completed the whole treatment and follow-up. After treatment, melasma in the observation group and the control group improved to varying degrees. The mMASI scores in the observation group at 0, 4, 8, 12, 16 and 20 week were 6.14±1.97, 5.05±2.01, 4.44±1.79, 3.41±2.45, 2.66±1.94, 2.33±1.99 and in the control group were 7.33±2.85, 6.74±2.84, 5.96±2.39, 5.01±2.27, 4.48±2.39, 4.31±2.37. The results of two-way repeated-measures ANOVA showed that there was a statistically significant difference in mMASI scores between observation time points (P time<0.05). The mMASI scores at each observation time point were lower in the observation group than those in the control group, and the differences between groups were statistically significant (P group<0.05). There was no interaction between intervention measures and time (P>0.05). There was no statistically significant difference in the distribution of PGA scores or patient satisfaction between the two groups (P>0.05). There were no obvious side effects in both groups.Conclusions  755 nm picosecond laser combined with traditional Chinese medicine mask is safe and effective in the treatment of melasma, and patients have good treatment experience.
    Association between ApoE gene polymorphism and cardiovascular and cerebrovascular diseases in Hebei Han nationality
    He Sha, Yuan Mengwei, Gao Yan, Gou Dongyun, Li Yang, Qiu Huiqing
    2023, 44(5):  852-858.  doi:10.3969/j.issn.1006-7795.2023.05.021
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    Objective  To analyze the distribution and clinical characteristics of apolipoprotein E(ApoE) gene polymorphism in Hebei Han population. Methods  A total of 4 641 inpatients who visited the First Hospital of Hebei Medical University from June 2018 to October 2019 were taken as the research object. Polymerase chain reaction (PCR)- fluorescent probe technology was used to detect the ApoE gene in the peripheral whole blood genome of patients. According to the ApoE genotype (excluding ε2/ε4),we divided the patients into E2 groups(ε2/ε2+ε2/ε3), E3 group(ε3/ε3) and E4 group(ε3/ε4+ε4/ε4), retrospectively analyze the distribution characteristics of ApoE gene polymorphism among the three groups, and compare the differences among the three groups in age, sex, clinical diagnosis and complications, hematological and biochemical indicators, carotid artery color ultrasound, and brain magnetic resonance angiography. Results  The incidence of Alzheimer's disease, myocardial infarction,  hyperlipidemia in E4 group was significantly higher than that in E2 and E3 groups (P <0.05). The detection of some hematological biochemical indexes showed that the values of triglyceride, total cholesterol, low-density lipoprotein cholesterol and lipoprotein a in ApoE gene E4 group were significantly higher than those in E2 and E3 groups, and the difference was statistically significant (P<0.05). There was no significant difference in the values of high density lipoprotein, fasting blood glucose, creatine kinase, uric acid, homocysteine between E2 and E3 groups. Conclusions  Compared with the homozygote of ApoE ε3 allele, the carriers of ε4 allele were associated with Alzheimer's disease, myocardial infarction,  hyperlipidemia and elevated levels of triglyceride, total cholesterol, low density lipoprotein cholesterol and lipoprotein a.
    The effects of comprehensive psychological intervention on executive and social functioning in stable schizophrenic patients
    Zhang Ying, Wang Ruomei, Li Gang, Li Lusha
    2023, 44(5):  859-864.  doi:10.3969/j.issn.1006-7795.2023.05.022
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    Objective  To explore the effect of comprehensive psychological intervention on improving executive and social functioning in patients with stable schizophrenia. Methods  Eighty patients with stable schizophrenia were included and randomly divided into 2 groups. The experimental group received comprehensive psychological intervention. The control group received only general medication provided by the hospital and routine psychological-related knowledge education. Symptom severity, executive functioning, and social functioning were assessed at baseline, and at the end of the intervention (week 12). Results  After 12 weeks of intervention, the total score, negative scale, and general psychopathology scale scores of Positive and Negative Syndrome Scale(PANSS) in the experimental group were lower than those in the control group(P<0.05). The numbers of Rpe and nRpe in Wisconsin Card Sorting Test (WCST) were lower than that in the control group(P<0.05). The reaction times of TMT-A and B were lower than that of the control group(P<0.05). The time consumption, stroop interference effect(SIE) time consumption, and SIE accuracy of cards A, B, and C in Stroop Color Word Test (CWT) were lower than those in the control group(P<0.05), while the accuracy of cards A, B, and C were higher than that in the control group(P<0.05). The score of Personal and Social Performance Scale(PSP) was higher than that of the control group(P<0.05). Conclusions  Comprehensive psychological intervention can help reduce negative symptoms, improve executive functioning, and enhance social functioning in patients with stable schizophrenia.
    ffect of intraoperative oxygen concentration on postoperative neurological function and complications in patients undergoing cerebrovascular recanalization
    Hu Zhengfang, Wang Juan, Jian Minyu, Han Ruquan
    2023, 44(5):  865-871.  doi:10.3969/j.issn.1006-7795.2023.05.023
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    Objective  To investigate the safety and efficacy of intraoperative normobaric hyperoxia as an auxiliary neuroprotective strategy combined with endovascular recanalization in the treatment of patients with ischemic cerebrovascular disease (ICVD). Methods  This is a single-center retrospective cohort study, including patients aged 60 and older with ICVD and operation duration≥2 h in Beijing Tiantan Hospital, Capital Medical University from January 2016 to September 2021 and received endovascular recanalization under general anesthesia. A total of 351 patients were divided into H group (100% O2, 109 cases) and L group (50% O2, 242 cases) according to the intraoperative inhaled oxygen concentration. The National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the degree of neurological deficit in stroke patients. Modified Rankin Scale (mRS) score was applied to evaluated the recovery status of neurological function in patients after stroke. We also compared the differences of NIHSS score and mRS score after operation and discharge, and postoperative complications (pneumonia, re-stroke, cerebral hemorrhage) between the two groups. Spearman correlation analysis was used to explore the correlation factors with NIHSS score. Results  There was no significant difference in the postoperative and discharge NIHSS score, mRS score and postoperative complication rate between the two groups (P>0.05). Compared to H group, the hospital stay in L group was significantly shorter (P<0.05). The relevant factor for postoperative NIHSS score were oxygen concentration, emergency, preoperative stenosis rate, stenosis length, hyperlipidemia, preoperative NIHSS score and preoperative mRS score. Conclusion  Although normobaric hyperoxia has limited effect as an adjuvant neuroprotective strategy based on vascular recanalization in patients with ICVD, it has no significant effect on the recent neurological recovery of patients, but it does not increase the incidence of postoperative complications.
    Correlation between residual lipoprotein cholesterol and acute myocardial infarction
    Feng Dan, Li Na, Hou Dongyan
    2023, 44(5):  872-876.  doi:10.3969/j.issn.1006-7795.2023.05.024
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    Objective  To investigate the correlation between residual lipoprotein-cholesterol (RLP-C) and acute myocardial infarction (AMI) by analyzing the changes of blood lipid levels in different subgroups of patients with coronary heart disease.Methods  Patients with coronary heart disease who were admitted to the Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University from January 2020 to January 2021 were selected as the study objects. The total of 266 patients with AMI were selected as the case group (AMI group) and 267 patients with non-AMI were selected as the control group (non-AMI). The RLP-C index and  atherogenic index of plasma(AIP) were calculated based on the formula. The relationship between RLP-C level and AMI was analyzed by univariate analysis and multiple Logistic regression model.Results  The results of univariate analysis showed that the level of RLP-C in AMI group was significantly higher than that in non-AMI group, and the difference was statistically significant (P<0.05). Multivariate Logistic regression showed that after controlling the interference effect of other factors, RLP-C was still an independent risk factor for AMI (P<0.05). Patients with elevated levels of RLP-C had an increased risk of AMI, and among many influencing factors, RLP-C was most closely related to AMI (OR=3.093, 95% CI: 1.658-5.771).Conclusions  Serum RLP-C level is associated with AMI, and the risk of AMI increases in patients with elevated RLP-C level.
    Recent progress on immunotherapy for tumor microenvironment of triple negative breast cancer
    Xu Jingxing, Zhou Quan, Ying Jianming
    2023, 44(5):  882-888.  doi:10.3969/j.issn.1006-7795.2023.05.026
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    Triple negative breast cancer (TNBC) is associated with high invasiveness, high metastasis,high risk of recurrence and metastasis. Currently, there is still a lack of effective molecular therapeutic targets, and the median survival time for patients with advanced disease is only 1 year, which is the worst prognosis for a subtype of breast cancer. It has been identified that there are a variety of tumor-associated immune cells and stromal cells in the tumor microenvironment(TME), which play a key role in the development, invasion and metastasis of TNBC, now an increasing numbers of studies are  focusing on the value of immunotherapy in TNBC. TME hosts many potential targets for immunotherapy, and the thorough exploration of TME may provide new perspectives for immunotherapy in TNBC. This study provides a comprehensive review of the latest advances in understanding the components of the TME in TNBC,and their associated targeted therapeutic strategies.
    Katalin Karikó and Drew Weissman won the Nobel Prize in Physiology or Medicine owing to their achievements in the development of mRNA vaccine against severe acute respiratory syndrome coronavirus 2
    hou Yan, Wu Wei
    2023, 44(5):  889-894.  doi:10.3969/j.issn.1006-7795.2023.05.027
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    On October 2, 2023 by Beijing Time, the Karolinska Institute of Sweden in Stockholm announced that Hungarian American scientist Katalin Karikó and American scientist Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine, in recognition of their discovery of nucleoside base modifications, which in turn contributed to the development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Here we will introduce the two scientists’ backgrounds, major scientific contributions and the significance of the discoveries.
    Quantum dots: essential seeds of nanotechnology—the 2023 Nobel Prize in Chemistry
    Wang Yixuan, Du Songrui, Jia Yunshu, Liu Wenjing, Wang Yuji
    2023, 44(5):  895-902.  doi:10.3969/j.issn.1006-7795.2023.05.028
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    On October 4th 2023,at approximately 5:45 PM Beijing time, the Royal Swedish Academy of Sciences had decided to award the 2023 Nobel Prize in Chemistry to American scientists Moungi G. Bawendi,Louis E. Brus and Russian scientist Alexei I. Ekimov for their discovery and study of quantum dots.