Basic & Clinical Medicine

Venous thromboembolism

Wang Chunmei

2024, 44(7): 905-905. doi:10.16352/j.issn.1001-6325.2024.07.0905

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Prevention strategies of venous thromboembolism in critically ill ICU patients

XIE Fangfei, LI Shuangling, WANG Chunmei

2024, 44(7): 906-911. doi:10.16352/j.issn.1001-6325.2024.07.0906

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Venous thromboembolism (VTE) includes deep venous thrombosis (DVT) and pulmonary embolism (PE). Patients in intensive care unit (ICU) are often at a high risk of VTE due to combining many risk factors. Prevention strategies of VTE in critically ill patients are crucial, including identification of risk factors, the risk assessment of thrombosis and bleeding, mechanical prophylaxis and drug prophylaxis, effect monitoring, and quality control. Since the risk of VTE in ICU patients is high, the risk of bleeding should not be ignored. It is a challenge for ICU physicians to comprehensively evaluate the risk of thrombosis and bleeding in critically ill patients and implement effective preventive and monitoring measures in time. This article reviews the relevant research progress on prevention strategies of VTE in critically ill patients in order to provide clinical evidence for the prophylaxis of VTE in critically ill patients.

Mechanism of Panax notoginseng saponins in the prevention of thrombosis

LI Peijuan, WANG Chunmei, ZHAO Qian

2024, 44(7): 912-915. doi:10.16352/j.issn.1001-6325.2024.07.0912

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Panax notoginseng saponins (PNSs) as the extracted bioactive components of Panax notoginseng, have a long history of application in prevention of thrombosis. PNSs down-regulate the expression of inflammatory factors, promoting endothelial cell growth, up-regulating the expression of anticoagulants and vasodilators, and regulating endothelial cell function; With multiple targets at which PNSs inhibit platelet adhesion, release, and aggregation; PNSs maintain the activity of the fibrinolytic system by regulating the dynamic balance of tissue type plasminogen activators and inhibitors; PNSs reduce blood viscosity, improve red blood cell indicators, and inhibit thrombosis through multiple pathways.

Prevention of venous thromboembolism in elderly patients

DING Mengxi, WANG Chunmei

2024, 44(7): 916-920. doi:10.16352/j.issn.1001-6325.2024.07.0916

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Venous thromboembolism (VTE) is a common disease with high morbidity and mortality. The incidence and mortality of VTE are higher in elderly patients and increased level of D-dimer, a thrombosis marker is positively related with age. Therefore, the diagnostic threshold needs to be adjusted to screen VTE with D-dimer level. Elderly patients may still have VTE after implementation of anticoagulant prevention, and increasing age is a high risk factor for bleeding after anticoagulant prevention. Whether elderly patients need to be monitored for anticoagulant prevention of VTE, and the relationship between age and VTE recurrence remains to be determined. In-depth research on the prevention of VTE in elderly patients and exploration of innovative VTE prevention strategies may orient future research.

Diagnosis and treatment of venous adventitial cystic disease

ZHANG Yanqi, YAN Bin, NING Yachan, YU Xueyuan, WANG Chunmei

2024, 44(7): 921-924. doi:10.16352/j.issn.1001-6325.2024.07.0921

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Venous adventitial cystic disease (VACD) is a rare vascular disease which often manifests as unilateral limb swelling, and so misdiagnosed as other diseases such as deep vein thrombosis. Color Doppler ultrasound, CT angiography and magnetic resonance imaging play a crucial role in the diagnosis of VACD. Surgical treatment is the main method for VACD, including cyst incision, cyst wall resection, cyst puncture, aspiration and cyst and vessel resection. The recurrence rate of VACD is relatively high, ranging from 20% to 83%. Enhancing the understanding of VACD, making accurate diagnoses and appropriate surgical operation are of great significance for improving treatment outcomes and reducing the recurrence rate.

Salidroside promotes proliferation and migration of human vascular endothelial cell line EA.hy926

CAO Qingwen, QI Lin, YU Bo, TIAN Chenchen, YUAN Haining, WANG Yue

2024, 44(7): 925-930. doi:10.16352/j.issn.1001-6325.2024.07.0925

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Objective To investigate the effect of salidroside (SAL) on the proliferation and migration of human vascular endothelial cell line EA.hy926. Methods The cells were divided into control group and test groups of 1,10 and 100 nmol/L SAL, 10 nmol/L SAL+2 μg/mL avastin (vascular endothelial growth factor(VEGF) blocker) group, 10 nmol/L SAL+2 μg/mL IgG (blocker negative control) group, 10 nmol/L SAL+8 μg/mL avastin group, 10 nmol/L SAL+8 μg/mL IgG group, 10 μmol/L YC-1[hypoxia inducible factor-1α(HIF-1α) blocker] group and 10 μmol/L YC-1+10 nmol/L SAL group. The proliferation and migration of EA.hy926 cells were detected by MTS assay and Transwell cell migration experiments. RT-qPCR and Western blot were used to measure the gene and protein level of HIF-1α and VEGF. The luciferase report gene experiment was used to find the effect of SAL on HIF-1α transcription activity of EA.hy926 cells.The guanylate cyclase activator (YC-1) was used as a HIF-1α blocker to verify potential effect of SAL on the expression of VEGF through HIF-1α. Results SAL significantly promoted proliferation of EA.hy926 cells (P＜0.05)and the proliferation promoting effect of SAL(10 nmol/L) was significantly reduced by the VEGF blocker bevacizumab avastin(2 μg/mL) (P＜0.05). SAL significantly promoted migration of EA.hy926 cells (P＜0.05), and this effect was significantly inhibited by avastin(8 μg/mL)(P＜0.05). SAL increased the expression of HIF-1α and VEGF gene and protein, and promoted the transcription of HIF-1α (P＜0.05).The level of HIF-1α and VEGF protein decreased by YC-1, a HIF-1α blocker(P＜0.05). Conclusions HIF-1α/VEGF pathway is potentially involved in SAL promoted proliferation and migration of EA.hy926 cells.

KAT8 promotes the proliferation of colorectal cancer cell lines by enhancing METTL3 expression

ZHANG Pengju, LI Jie, ZHANG Mengdi, SUN Shaoke, XU Yinzhe

2024, 44(7): 931-939. doi:10.16352/j.issn.1001-6325.2024.07.0931

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Objective To investigate the role and mechanism of lysine acetyltransferase 8(KAT8) on the proliferation of colorectal cancer cells. Methods The expression of KAT8 in cancerous tissues and adjacent tissues of colorectal cancer patients was analyzed by RNA-seq data of TCGA database. Cell proliferation was detected by colony-forming unit assays and CCK8. The GEO database was used to analyze the differential genes of KAT8 knockdown cells and control cells and perform functional pathway enrichment analysis. In the colorectal cancer database hosted on cBioPortal, that conducted an analysis examining the correlation between KAT8 and genes in the regulation of N6-methyladenosine(m6A) modification. Western blot technique was employed to assess the protein expression levels of KAT8 and METTL3. Results Compared to human normal colorectal tissue, KAT8 was highly expressed in colorectal cancer(P＜0.05). Knockdown or selective inactivation of KAT8 inhibited colorectal cancer cells proliferation (P＜0.05). In colorectal cancer cell lines, knocking down KAT8 reduced m6A modification levels (P＜0.05). Knocking down KAT8 inhibited METTL3 expression (P＜0.05). Over-expression of METTL3 reversed cell proliferation which was inhibited by knockdown KAT8(P＜0.05). Conclusions KAT8 facilitates the proliferation of colorectal cancer cell lines through regulation of METTL3-mediated m6A modifications.

Disodium malonate impairs human sperm motility by inhibiting succinate dehydrogenase activity

PENG Zhen, WEN Qin, LU Jing, TU Zeliang, CHENG Yimin

2024, 44(7): 940-946. doi:10.16352/j.issn.1001-6325.2024.07.0940

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Objective To investigate the impact of succinate dehydrogenase (SDH) on the modulation of human sperm functions. Methods The isolated human sperm were co-incubated with different concentrations (10, 20, 40 mmol/L) of SDH inhibitor disodium malonate for one or two hours. The activity of the SDH was measured by commercially available reagent kit, while the protein level of the SDH catalytic subunit SDHA was determined through Western blot analysis. Sperm functions were analyzed:1)The impact of disodium malonate on important motility parameters of un-capcitated sperm including progressive motility rate (PR), total motility (TM), average pathvelocity (VAP)and the ability of capacitated sperm to penetrate viscous media were be assessed using a computer aided semen analysis system. 2) Effect of disodium malonate on sperm survival rate was evaluated using the Eosin-Nigrosin microscopy. 3) The incidence of acrosome reaction in capacitated sperm was be detected by PSA-FITC staining assay following disodium malonate treatment. Results Disodium malonate had no effect on expression of SDH catalytic subunit SHDA protein in human sperm. However, it inhibited the catalytic activity of the SDH, sperm forward motility, total motility, and the ability of sperm to penetrate viscous media. These inhibitory effects were positively correlated with the concentration of disodium malonate. Furthermore, disodium malonate had no any influence on the occurrence of spontaneous acrosome reaction in capacitated sperm. Conclusions Disodium malonate impairs human sperm motility by inhibiting succinate dehydrogenase activity.

Purification and in vitro functional validation of exosomes from 293T cells with over-expressed membrane-localized IL-3

GAO Lu, CAI Menghua, XU Yi, HE Wei, CHEN Hui, ZHANG Jianmin

2024, 44(7): 947-953. doi:10.16352/j.issn.1001-6325.2024.07.0947

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Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro, so as to lay a foundation for in vivo function verification in animal models of Alzheimer′s disease. Methods Using the patented structure of the group, a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged. Stable cell strain over-expressing IL-3 was screened. The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence. Il-3-exosomes were purified by ultra filtration centrifugation, the exosmic morphology was observed by transmission electron microscope, the size distribution and concentration of exosomes were detected by nano-flow analysis, and the expression of IL-3 and exosome related marker proteins were detected by Western blot. The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluorescence. Results Through vector construction, virus infection, screening and verification of puromycin, 293T cell strain with stable over-expression membrane-anchored IL-3 was obtained. The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope. Western blot results proved the presence of CD63, ALIX, TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control, that suggested the successful purification of IL-3-exosomes. The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocytosis of Aβ amyloid by BV-2 cells in vitro. Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro, which promote the phagocytosis of microglia, there for provides a new idea for the clinical treatment of Alzheimer′s disease.

Phenotype of piebaldism resulted from heterozygous large fragment KIT deletion in one family

ZHANG Rui, TAN Yan, MA Donglai, WANG Rongrong, ZHANG Xue

2024, 44(7): 954-958. doi:10.16352/j.issn.1001-6325.2024.07.0954

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Objective To identify the pathogenic mutations in a family with piebaldism. Methods Clinical information and peripheral blood were collected from the patient with piebaldism and their parents. Whole exome sequencing was performed to identify the potential pathogenic mutations. QPCR was used to determine the deletion of the target gene, while gap-PCR and Sanger sequencing was used to determine the size and the specific deletion site. Results The proband had a heterozygous deletion mutation of approximately 1.74 Mb located at chromosome 4, including a full length of the pathogenic gene KIT for mottled disease and it was the smallest micro deletion causing isolated piebaldism due to the loss of the KIT. Conclusions The heterozygous deletion including the KIT is a potential cause of the piebaldism phenotype found in this family.

DDX60 promotes expression of type Ⅰ interferon in PBMCs from patients with systemic lupus erythematosus

YUAN Xun, WANG Yuyang, MENG Shu

2024, 44(7): 959-964. doi:10.16352/j.issn.1001-6325.2024.07.0959

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Objective To explore the role of DExD/H box helicase 60(DDX60) in the development of systemic lupus erythematosus (SLE) by regulating the dsDNA-cGAS-IFN-Ⅰ pathway. Methods Differences in DDX60 mRNA level in peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy people were examined by analyzing RNA sequencing data and verified by RT-qPCR. The correlation between DDX60 mRNA level in PBMCs and disease activity of SLE patients was analyzed. Whether DDX60 was an interferon-stimulated gene (ISG) was clarified by interferon-alpha (IFN-α) stimulation of human acute monocyte leukemia cell line THP-1. The mRNA level of interferon-beta1 (IFNB1) was detected by RT-qPCR after silencing and knockdown of DDX60 and followed by double-stranded DNA (dsDNA) poly (dA:dT) transfection. Results RNA sequencing data and RT-qPCR result found high expression of DDX60 in PBMCs of SLE patients. DDX60 mRNA level in PBMCs was positively correlated with disease activity of SLE patients. IFN-α induced THP-1 cells to express DDX60, suggesting that DDX60 was an ISG. Silencing DDX60 resulted in a decrease in poly (dA:dT)-induced IFNB1 mRNA level. Conclusions DDX60 is highly expressed in PBMCs of SLE patients and involved in the development of SLE through the positive feedback loop of IFN-Ⅰ-DDX60-dsDNA-cGAS-IFN-Ⅰ, which suggests that DDX60 may be a target for the clinical diagnosis and treatment of SLE. The result of this research may support diagnosis and prognosis evaluation of SLE patients.

Impact of MAFB on polarization and function of tumor associated macrophages

CHEN Xiaotian, CHEN Chong, LUO Yunping

2024, 44(7): 965-973. doi:10.16352/j.issn.1001-6325.2024.07.0965

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Objective To investigate the impact of the MAFB transcription factor on macrophage polarization phenotype and function. Methods Analysis of correlation of MAFB expression with survival period of patients of breast cancer and lung adenocarcinoma was performed by RNA-seq data from the Kaplan-Meier database. Flow cytometry was applied to detect MAFB expression in primary human monocytes. Expression of MAFB mRNA or protein of human acute monocytic leukaemia cell line(THP-1) was detected by RT-qPCR or Western blot. Detection of macrophages phenotypes was performed by macrophages polarization in vitro, co-culture, RT-qPCR and flow cytometry. Phagocytosis assay was used to assess changes in phagocytic ability of macrophages. In vitro killing assay to evaluate changes in tumor-killing ability of macrophages. Results Compared to the MAFB low-expression group, patients with high MAFB expression in breast cancer and lung adenocarcinoma exhibited a decreased survival period(P＜0.05). Protein interaction networks showed a correlation between MAFB protein and macrophage polarization proteins. Compared to other cell type, MAFB was specifically highly expressed in human monocyte-macrophage cells. Phorbol myristate ester(PMA) induced an increased MAFB expression in THP-1 cells (P＜0.05). Knockdown of MAFB inhibited the expression of M2-related genes (P＜0.05). Co-culture with tumor cells and knockdown of MAFB suppressed expression of polarization gene (P＜0.05). Knockdown of MAFB did not affect the phagocytic abilityP＞0.05) but enhanced tumor-killing ability of macrophages (P＜0.05). Conclusions This investigation proves potential function of MAFB transcription factor in regulation of macrophage M2 polarization and anti-tumor effect in solid tumors.

Decrease of lncRNA-RMRP expression inhibits proliferation and invasion of human lung cancer cell line A549

ZHENG Hong, CHEN Xiaoxia, HAN Lizhou, CHEN Miao, HUANGFU Juan

2024, 44(7): 974-978. doi:10.16352/j.issn.1001-6325.2024.07.0974

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Objective To investigate the effect of inhibiting the expression of RNA component of mitochondrial RNA processing endoribonuclease(RMRP) on the proliferation and invasion of human lung cancer cell line A549 in order to provide evidence to support the research on NSCLC mechanism. Methods A total of 122 cases of patients who underwent surgical treatment were selected in Jiaozuo People′s Hospital from March 2016 to March 2021. In the same period, 50 healthy people from physical examination center were selected as the control group. RT-qPCR was used to detect the expressions of RMRP in blood and tissues. Human lung cancer cell line A549 was cultured and divided into si-RMRP group, siRNA-NC group and blank group.RT-qPCR, CCK-8 and Transwell assays were used to detect the expression of RMRP, proliferation activity and cell counting of invasive cells. Results The relative expression level of RMRP in the blood of NSCLC patients was significantly higher than that of control group (P＜0.001). The relative expression level of RMRP in NSCLC tissues was significantly higher than the adjacent tissues (P＜0.001). The relative expression level of RMRP in blood and tissues of patients with poorly differentiated, lymph node metastasis and TNM stage Ⅲ compared with moderate to highly differentiated, no lymph node metastasis and TNM stage Ⅰ-Ⅱ were significantly increased (P＜0.05). The relative expression level of RMRP in the cells of the si-RMRP group was lower than that of blank and the siRNA-NC group (P＜0.001). Compared with the blank group and the siRNA-NC group, the absorbance (A) value of cells at 24, 48, 72 and 96 h in the si-RMRP group was decreased (P＜0.05). The number of invasion cells in the si-RMRP group was lower than that in the blank group and the siRNA-NC group (F=27.765, P＜0.001). Conclusions The relative expression levels of RMRP in blood and tissues of NSCLC patients are increased. Down-regulation of the expression of RMRP gene in A549 cells can inhibit cell proliferation and reduce cell invasion.

Antihypertensive drug-related gene polymorphisms in patients with primary hypertension in Guiyang region

ZOU Wenbing, WANG Anxian, CAO Zhengyuan

2024, 44(7): 979-983. doi:10.16352/j.issn.1001-6325.2024.07.0979

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Objective To analyze the distribution bio-relationship of loci related antihypertensive drug efficacy in patients with essential hypertension (EH) in Guiyang region to support the development of clinical guidance for individualized medication of hypertension patients in this region. Methods A total of 406 EH patients who visited the Cardiology Department of Guiyang Hospital from December 2020 to December 2021 were collected as the study subjects and ligase sequencing method was applied to detect 7 gene loci of antihypertensive drugs. The distribution of gene loci in EH patients of different genders and from different geographic regions was evaluated. Results The mutation frequencies of the seven genes, CYP2D6*10(c.100 C＞T),CYP2C9*3(c.1075 A＞C),ADRB1(c.1165 G＞C),AGTR1(c.1166 A＞C),ACE(I/D),NPPA(T2238C) and CYP3A5*3(A6986G) were 47.29%, 5.91%, 73.15%, 6.65%, 34.24%, 0.49%, and 69.70% respectively; There was no significant difference in distribution frequency of hypertension drug related gene polymorphisms among different genders. Conclusions The distribution frequency of alleles in 7 antihypertensive drug efficacy related loci is not related to gender of patients.EH patients in Guiyang region are more sensitive to β-blockers and calcium antagonists, but less sensitive to other types of antihypertensive drugs. Therefore, the dose administered should be adjusted appropriately when using β-blockers and calcium antagonists.

Increased exercise is associated with reduced insulin resistance and cardiovascular risk factors in individuals with newly diagnosed diabetes

QI Mengya, LI Yuxiu, YU Jie, ZHANG Huabing, XU Lingling, LI Wei, PING Fan

2024, 44(7): 984-988. doi:10.16352/j.issn.1001-6325.2024.07.0984

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Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status. Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research. Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance, insulin sensitivity, neck circumference (NC) and neck circumference height ratio (NHtR) in the subjects with different glucose metabolism status, the relationship between NC and insulin resistance and insulin sensitivity in different glucose metabolism groups. Results 171(62.9%) Subjects with diabetes were intervened by exercised every day. Spearman correlation analysis showed the correlation between exercise frequency and tri-glyceride triglyceride-glucose index (TyG index) (r=-0.120, P＜0.05) and NC (r=-0.168, P＜0.05) were negatively correlated. In subjects with diabetes, NC was positively correlated with triglycerides(TG) (r=-0.100, P＜0.05), homeostasis model assessment of insulin resistance(HOMA-R) (r=-0.163, P＜0.05), total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214, P＜0.05) and TyG index (r=-0.156, P＜0.05). Conclusions Increased frequency of exercise is associated with reduced NC, improved insulin resistance, and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes. Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

Recombinant human lactoferrin accelerates fracture healing in rats by promoting osteoblast proliferation

YE Junwu, ZHENG Xuzhou, FEI Lincong, LI Shuyang, YANG Tianfu

2024, 44(7): 989-996. doi:10.16352/j.issn.1001-6325.2024.07.0989

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Objective To investigate the effect of recombinant human lactoferrin (rhLF) on fracture healing in rat models with femur fracture and the proliferation of rat primary osteoblasts. Methods Male rats were randomly divided into 3 groups: simple fracture group (SF group), collagen film-treated group (CF group) and rhLF-compound collagen lamination film-treated group (CLF group). The fracture healing was observed by X-ray image and histological microscopy with HE and Masson staining. The newborn SD rats with osteoblasts were treated with different concentrations of rhLF, and osteoblast proliferation was detected by MTT method. Results The bone scabs in the CLF group were significantly larger than those in the SF and CF groups at 1, 2, and 3 weeks postoperatively (P＜0.05). There was no difference in the comparison between the groups at 4th week. The proliferation of cartilaginous and sclerotic bone scabs in the CLF group was more pronounced and showed the appearance of mature trabeculae and lamellar bone with a high degree of maturation of the bone scabs. The groups with 100 mg/L and 500 mg/L rhLF showed a significant decrease in A value for rat primary osteoblasts cultured in vitro as compared with the control group(P＜0.05). The A value increased significantly at the first day (P＜0.05). The concentration of rhLF increased at the fifth and tenth days. Conclusions rhLF has an accelerating effect on fracture healing which is manifested by fast scab formation, large volume and high maturity. The rhLF can promote the proliferation of osteoblasts cultured in vitro, and the effect is mainly manifested in the rapid proliferation stage of osteoblasts.

Early differential value of serum SAA4 and SOCS1 for spinal tuberculosis and pyogenic spondylitis

HU Chaoxing, LIANG Qiudong, WU Dapeng

2024, 44(7): 997-1001. doi:10.16352/j.issn.1001-6325.2024.07.0997

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Objective To investigate the value of serum amyloid A4 (SAA4) and suppressor of cytokine signaling 1 (SOCS1) in the early differential diagnosis of spinal tuberculosis (STB) and pyogenic spondylitis (PS). Methods The clinical information from STB patients (STB group, n=62) and PS patients (PS group, n=52) who visited the First Affiliated Hospital of Xinxiang Medical College from January 2019 to June 2021 were collected, and another 50 healthy individuals from examinations clinic in the same period were taken as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to measure the expression of serum SAA4 and SOCS1; Logistic regression was applied to analyze the influencing factors of identifying STB and PS; Receiver operating characteristic (ROC) curve was applied to analyze the differential value of serum SAA4 and SOCS1 for STB and PS. Results Compared with the control group, serum SAA4 level was increased and SOCS1 level decreased in patients from STB and PS groups (P＜0.05), while the level of SAA4 and SOCS1 in the STB group was higher than those in the PS group (P＜0.05); Logistic regression analysis showed that serum SAA4, and SOCS1 were predictive factors for distinguishing STB from PS (P＜0.05); ROC curve results showed that the area under the curve(AUC) of SAA4 and SOCS1 for distinguishing STB and PS separately was 0.833 and 0.872 with sensitivity of 75.8% and 75.8% and specificity as 65.1% and 66.9% respectively. The AUC of the combination of STB and PS was 0.947, with sensitivity and specificity of 88.7% and 78.0% respectively and the AUC identified by the combination of the two was obviously higher than that identified by SAA4 and SOCS1 alone (Z=2.683, 2.015, P＜0.05). Conclusions The serum levels of SAA4 and SOCS1 in STB patients are significantly higher than those in PS patients and both can be used as early differential indicators for STB and PS. Combined measurement can improve the effectiveness of differential diagnosis.

Repair effect of human amniotic mesenchymal stem cells on uterine scars in rats

SONG Jia, ZHAO Feng, ZHANG Ting, XU Jing, SUN Jingli, CHEN Zhenyu

2024, 44(7): 1002-1007. doi:10.16352/j.issn.1001-6325.2024.07.1002

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Objective To exploring the effect of human amniotic mesenchymal stem cells(hAMSCs) on the repair of rat uterine scars. Methods The hAMSCs were isolated and cultured,Female SPF grade SD rats were selected for full-thickness incision of uterine wall and then implanted with hAMSCs. On the 30th day after operation, the uterine incision was examined histologically.ImageJ image analysis software was used to analyze and to compare the thickness of uterine myometrium and the percentage of fibrotic area in each group.Immunohistochemical method was used for detecting the percentage of positive areas of α-SMA, TGF-β1, and Ki-67. Results Compared with the PBS group, the hAMSCs group showed significant thickening of the uterine muscle layer and fibrotic area was decreased, The positive expression of α-SMA, and Ki-67 significantly increased(P＜0.05), while the expression of TGF-β1 was significantly reduced(P＜0.05). Conclusions The hAMSCs may promote the repair of uterine incision scars by reducing the formation of scar fibrosis and promoting the proliferation of smooth muscle cells in uterine scars.

Clinical and gene variation characteristic of 75 cases of hepatolenticular degeneration in children

ZHANG Simin, WANG Wei, MA Mingsheng, QIU Zhengqing

2024, 44(7): 1008-1012. doi:10.16352/j.issn.1001-6325.2024.07.1008

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Objective To investigate the clinical characteristics of the hepatolenticular degeneration in children, and to clarify the significance of gene diagnosis in children with hepatolenticular degeneration. Methods A total of 75 patients with hepatolenticular degeneration were enrolled in the Department of Pediatrics, Peking Union Medical College Hospital from 2011 to 2018. All of them carried out a generation of gene sequencing for ATPase Cu²⁺ transporting beta polypeptide (ATP7B) gene and multiplex ligation-dependent probe amplification (MLPA) analysis. Results Among the 75 pediatric patients, 55 patients were asymptomatic and had elevated aminotransferases as the incidental findings. All the pediatric patients had decreased ceruloplasmin. Seventy-two of pediatric patients had 24-hour urinary copper＞40 μg/d. There were 16 cases that had Kayser-Fleischer(K-F) rings. Sixteen six out of 75(21.33%)cases were diagnosed clinically and 15 cases were＞7 years old. All the remaining patients needed genetic diagnosis. Sixty-six patients had two mutations and 9 patients had only one mutation, 1 had no mutation. Forty eight different mutations were found to be localized in ATP7B gene. These mutations included 32 missense mutations, 6 splice mutations, 5 deletion mutations, 2 repeated mutations, 2 insert mutations and 1 nonsense mutations. The most frequently three mutations were c.2333G＞T,p.R778L,c.2621C＞T, p.A874V,c.2975C＞T, p.P992L,whose allele frequencies were 30.49%,14.89%,9.92%. Conclusions The research showed that in young aged patients, the nervous system symptoms are not obvious and the positive rate of laboratory tests are lower than adults so is a challenge to clinical diagnosis. So Genetic testing is of great significance for the early diagnosis and early treatment of disease in pediatric patients.

Correlation between hip fracture and RDW as well as N-MID OC/β-CTX ratio in elderly women

LIU Xiaoli, ZOU Ming

2024, 44(7): 1013-1017. doi:10.16352/j.issn.1001-6325.2024.07.1013

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Objective To explore the correlation between erythrocyte distribution width (RDW), medium molecular fragment of osteocalcin N segment (N-MID OC)/ special sequence β carboxy-terminal peptide of collagen I (β-CTX) ratio and the risk of hip fracture in elderly women. Methods A total of 731 female patients over 60 years old who were hospitalized in Sichuan Orthopedics Hospital from January 2021 to December 2021 were selected. There were 375 cases with fracture and 358 cases without fracture. The clinical baseline data were collected. Binary logistic regression model was used to analyze the correlation between RDW-CV, N-MID OC/β-CTX ratio and hip fracture in elderly women. Results Logistic regression analysis showed that age, RDW-CV, N-MID OC/β-CTX, calcium (Ca) and phosphorus (P) levels were risk factors for hip fracture in elderly women. The values of RDW-CV and N-MID OC/β-CTX were divided into three levels in equal proportion after ordering from small to large, and the results showed that the higher the RDW-CV and the lower the N-MID OC/β-CTX ratio, the higher the risk of hip fracture in elderly women (P＜0.05). According to receiver operating characteristic curve (ROC), both single test and combined test may be used to diagnose fracture, but combined test may improve the diagnostic performance, with area under curve (AUC) of 0.729, sensitivity and specificity of 60.53% and 75.42%, respectively. Conclusions RDW-CV and N-MID OC/β-CTX ratio are associated with hip fracture in elderly women.

Comparison of adverse reactions and effects of IMRT combined with different chemotherapy regimens in patients with early stage esophageal squamous cell carcinoma

ZHANG Wei, ZHANG Zhen, LIU Dong, JIANG Houzhou, LIANG Wei

2024, 44(7): 1018-1022. doi:10.16352/j.issn.1001-6325.2024.07.1018

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Objective To investigate the adverse reactions, short-term and long-term effects of DP(docetaxel+cisplatin) regimen and PF(cisplatin+5-fluorouracil) regimen combined with intensity modulated radiation therapy(IMRT)in patients with distant metastatic esophageal squamous carcinoma. Methods From January 2021 to June 2022, 96 patients with non-metastatic esophageal squamous carcinoma were randomly divided into 48 cases in Taihe County People′s Hospital of Fuyang City, Anhui province and 48 cases in control group. Which was treated with DP plus IMRT. The observation group was treated with PF plus IMRT. The occurrence of adverse reactions and the effect of both groups were compared. Results Compared with control group, the difference in the incidence of adverse reaction was not significant. The total effective rate was higher in the observation group than in that in control group (83.3% vs 62.5%, P＜0.05). Overall survival, 1-year survival, 3-year survival in observation and in control group were 70.83% vs 50.00%, 79.36% vs 60.23% and 65.10% vs 35.52%. Long-term outcomes were observed and compared. The median survival time was 34.40 months in the observation group and 18.3 months in control group (P＜0.05). Conclusions DP regimen combined with IMRT is more effective than PF regimen combined with IMRT in the treatment of patients with distant metastatic esophageal squamous carcinoma.

Progress on the role of transketolase in occurrence and treatment of diabetes and its complications

WANG Zeying, LIU Zhi, TAI Yu, YANG Zhongbin, SU Yan

2024, 44(7): 1023-1028. doi:10.16352/j.issn.1001-6325.2024.07.1023

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Transketolase (TKT) is an important enzyme that catalyzes the non-oxidative phase group transfer reaction of pentose phosphate pathway (PPP), and is involved in the metabolism of various energy substances in the body, such as glucose, ribose, nucleotides and lipids. TKT can reduce oxidative stress, inflammation, atherosclerosis, endothelial dysfunction and Tau protein phosphorylation by inhibiting advanced glycated end-produces(AGEs) produced by non-enzymatic glycosylation (NEG) of proteins and lipids in a high-glucose environment improving blood glucose, glucose tolerance and β cell function so to prevent and treat diabetes and its complications. This article reviews research progress on the mechanism of TKT in the treatment of diabetes mellitus and its complications.

Mechanism of inducing microglial inflammatory response in patients with depression

ZHANG Hao, SUN Hao, LIAO Hong

2024, 44(7): 1029-1033. doi:10.16352/j.issn.1001-6325.2024.07.1029

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Microglial inflammatory response is a pathological process frequently found in patients with depression and in animal models, which is believed to be closely related to depression. The potential mechanisms of inducing microglial inflammatory response by depression includes the direct or indirect regulation of glucocorticoid level changes after activation of the hypothalamic-pituitary-adrenal (HPA) axis, the effect of intestinal microbial metabolites through immune and neural pathways in the brain-gut axis, and the direct activation of damage associated molecular patterns (DAMPs) in microglia.

Metabolic abnormalities in hyperoxia-induced lung diseases of neonates

HE Guangliang, WANG Tao, LIU Lei, ZHOU Jian, YE Min

2024, 44(7): 1034-1038. doi:10.16352/j.issn.1001-6325.2024.07.1034

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High oxygen(hyperoxia) concentration may damage multiple organs and systems in newborns, such as the lung, brain and intestines. Metabolic abnormalities are important early events in the pathogenesis of neonatal hyperoxia related pulmonary diseases. This article reviews the increased glucose and lipid metabolism as well as dys-regulation of amino acid metabolism after hyperoxia related bronchopulmonary dysplasia in newborns. The potential mechanism may be that the high oxygen concentration increases formation of mitochondrial reactive oxygen species (mtROS), and also change the mitochondrial dynamics of neonatal bronchopulmonary dysplasia, leading to reduction of mitochondrial fusion, enhances fission and autophagy. This study also finds that many metabolism-related enzymes and metabolites are changed during hyperoxia related diseases. However, clinical research has not yet been conducted. Future research should focus on combining metabolic profiles with multi omics data, including transcriptome sequencing, genomics and proteomics to identify potential biomarkers and therapeutic targets for hyperoxia related neonatal lung injury in order to develop new strategies for the treatment of metabolic abnormalities resulted from neonatal hyperoxia related pulmonary diseases.

Eukaryotic elongation factor 2 kinase is a potential new target for the treatment of tumors

LI Yang, ZHU Lei

2024, 44(7): 1039-1043. doi:10.16352/j.issn.1001-6325.2024.07.1039

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Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca²⁺/ CAM-dependent protein kinase, which inhibits the activity of substrate eEF2 by phosphorylating eEF2 to prevent protein synthesis, promote tumor cell proliferation, invasion, metastasis and to regulate tumor microenvironment. The eEF2K is “α-kinase” member of the atypical protein kinase family and has little sequence homology with typical protein kinases. Targeting eEF2K can avoid the toxic side effects caused by most kinases, so it is considered as a potential molecular target for tumor targeted therapy.

Factors associated with lymphangioleiomyomatosis progression and mortality

WANG Luyi, XU Kaifeng

2024, 44(7): 1044-1048. doi:10.16352/j.issn.1001-6325.2024.07.1044

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Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease characterized by diffuse cystic lesions that primarily affects women of reproductive ages and leads to respiratory failure at the end stage of the disease, and significantly impacts patients' quality of life. The clinical use of mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus) has moderated the rate of disease progression and significantly improved the survival in LAM patients. During the clinical diagnosis, treatment, and follow-up of LAM disease, the clinical characteristics and the course of the disease of different LAM patients are heterogeneous which might suggest differences in disease progression and long-term prognosis. The present review summarizes the progress of research on risk factors for LAM progression and mortality in order to optimize individualized intervention protocols in clinical practice and to improve long-term prognosis of patients.

Research progress on the role of FOXC1 in the development of digestive system cancer

JIN Qing, DING Youming

2024, 44(7): 1049-1053. doi:10.16352/j.issn.1001-6325.2024.07.1049

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forkhead box protein C1(FOXC1) is a cancer-related transcription factor that plays an important role in various signaling pathways related to cancer development.FOXC1 is involved in the regulation of cancer cells from many aspects, including proliferation, metastasis and recurrence.FOXC1 can promote cell cycle progression and cell proliferation by up-regulating the expression of oncogenes, such as cyclin D1.FOXC1 promotes epithelial-mesenchymal transition (EMT), in which cells change from polarized epithelial cells to cells with stromal characteristics, which contributes to tumor cell infiltration and migration.FOXC1 may play a role in tumor angiogenesis by regulating genes associated with angiogenesis.FOXCI can enhance cell migration and invasion by regulating reactive oxygen species and activating β-catenin expression.In summary, FOXC1 functions through a variety of mechanisms.

Application of TBL and workshop integrated teaching method in clinical training of gynecological oncology

TAN Shufen, HE Lipin, YANG Linlin, YANG Xielan, YANG Hongying, YAO Mingjiao, LI Shuqing

2024, 44(7): 1054-1057. doi:10.16352/j.issn.1001-6325.2024.07.1054

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Objective To develop a teaching strategy which is suitable for training talents and improving teaching quality in field of clinical gynecological oncology. Methods Seventy-eight clinical students of grade 2020 in a medical university were divided into control group (n=38) and research group (n=40). The “3+2” teaching mode of team-based learning (TBL) and workshop (WS) were adopted, and the learning outcome was evaluated at preview preparation, knowledge application and the questionnaire survey of students, so as to promote the cultivation of clinical reasoning of medical students. Results Compared with traditional teaching method, TBL+WS teaching group had better academic performance.The difference of before class tests and final exams was more significant [17.53±6.15 points and (76.81±5.10)points, respectively, P＜0.001].However, among the eight dimensions of the classroom teaching questionnaire, the teaching quality dimension was the highest (97.5%). More students think that this model had a positive effect on cultivating clinical thinking and developing new knowledge. Conclusions This integrated teaching strategy improves the quality of obstetrics and gynecology teaching and suppots students' capacity building on clinical reasoning .

Application of Peyton′s four-step teaching method in clinical internship teaching of urology

DONG Dexin, WANG Wenda

2024, 44(7): 1058-1060. doi:10.16352/j.issn.1001-6325.2024.07.1058

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Objective To assess the application effect of Peyton's four-step teaching method in clinical internship training of urology. Methods Ten clinical interns rotated in urology department of Peking Union Medical College Hospital from April 2023 to February 2024 were randomly divided into a study group and a control group with seven in each. The study group used Peyton′s four-step teaching method while the control group used classical method. After one month of rotating training, two groups of interns were evaluated by theoretical test and clinical skill assessments, and a survey by questionnaire was performed to evaluate the effectiveness of the training. Results The theoretical scores of the study group and the control group were 93.60±3.05 vs 91.80±2.39 and the clinical skills assessment scores were 92.00±1.87 vs 86.80±3.27,the difference was statistically significant (P＜0.05). In terms of clinical skills, there was a significant improvement in clinical performance. The results of questionnaire survey showed that the Peyton's teaching group is more comfortable by both trainees and trainers, as compared to that of control group. Conclusions The application of the Peyton's four-step teaching method significantly improves operational skills of the trainees. Both the faculty staff and students are satisfied with the Peyton′s four-step teaching method, which is suitable for clinical application in urology internship training.

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