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    Basic research
    Exploration of the relationship between nicotinamide metabolism-related genes and osteoarthritis
    DENG Qingsong, ZHANG Changqing, TAO Shicong
    2024, 44 (2):  145-160. 
    doi: 10.3969/j.issn.1674-8115.2024.02.001

    Abstract ( 206 )   HTML ( 28 )   PDF (5348KB) ( 198 )  

    Objective ·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis, and identify key genes with diagnostic value and therapeutic potential. Methods ·By using "Osteoarthritis" as a search term, GSE12021, GSE55235, and GSE55457 were obtained from the GEO database, with GSE55457 being used as the validation set. After removing batch effects from the GSE12021 and GSE55235 datasets, the standardized combined dataset was obtained and used as the training dataset. Differentially expressed genes (DEGs) were identified from the training dataset. All nicotinamide metabolism-related genes (NMRGs) were obtained from the GeneCards and MSigDB databases. The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes (NMRDEGs). Gene set enrichment analysis (GSEA) was performed on the training dataset, while gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on NMRDEGs. Key genes were selected by using least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the immune cell infiltration type. Interactions networks and drug molecule predictions were obtained for these key genes' mRNA with the DGIdb, ENCORI, and CHIPBase databases. siRNA was used to knock down the key genes in chondrocytes, and then real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of chondrogenesis-related genes. Results ·Seven NMRDEGs, including NAMPT, TIPARP, were discovered. GO and KEGG analysis enriched some signaling pathways, such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway. GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway. Key genes NPAS2, TIPARP, and NAMPT were identified through LASSO and SVM analysis, and used to construct an osteoarthritis diagnostic model. The validated results showed that the diagnostic model had high accuracy. Immune infiltration analysis results obtained by ssGSEA showed significant differences (all P<0.05) in 15 types of immune cells, including macrophages. Seven potential small molecules targeting key genes were identified, along with 19 miRNAs with the sum of upstream and downstream >10, 19 transcription factors with upstream and downstream >7, and 27 RNA binding proteins with clusterNum >19. The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes. Conclusion ·Through bioinformatics analysis, key genes related to nicotinamide metabolism, NPAS2, TIPARP, and NAMPT, are discovered, and an osteoarthritis diagnostic model is constructed.

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    Effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6
    LI Huxiao, LI Xiaotian, ZHAO Xuri, ZHANG Huanyu, ZHOU Wei, SONG Zhongchen
    2024, 44 (2):  161-168. 
    doi: 10.3969/j.issn.1674-8115.2024.02.002

    Abstract ( 96 )   HTML ( 18 )   PDF (3960KB) ( 87 )  

    Objective ·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6. Methods ·The HN6 cell line was selected, cultivated, and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis: control group, 3.125 μg/mL group, 6.25 μg/mL group, 12.5 μg/mL group, 25 μg/mL group, 50 μg/mL group, and 100 μg/mL group. After 24 and 48 h of cultivation, CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity. Subsequent experiments were divided into control group, 25 μg/mL group and 50 μg/mL group. Flow cytometry was used to examine the effects of gingipain extract on cell cycle. Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability. Real-time PCR (RT-PCR) and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells. Results ·Stimulated with gingipain extract for 24 h, the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL (P=0.025), 50 μg/mL (P=0.000), and 100 μg/mL (P=0.049) groups compared to the control group. After 48 h, proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024), 12.5 μg/mL (P=0.006), 25 μg/mL (P=0.000), 50 μg/mL (P=0.000), and 100 μg/mL (P=0.000) groups compared to the control group. Cell cycle analysis revealed that, after 24 h of gingipain stimulation, the proportion of HN6 cells in the G1 phase decreased, while the proportion in the S+G2 phase significantly increased compared to the control group (25 μg/mL group: P=0.024; 50 μg/mL group: P=0.001). Compared to the control group, the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased (P=0.001). Compared to the control group, the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased. RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased, the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased, while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group. Conclusion ·Gingipain extract could promote proliferation, migration, and invasion of oral squamous cell carcinoma HN6 cells.

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    Study on intercellular communication and key genes of smooth muscle cells in human coronary atherosclerosis based on single cell sequencing technology
    SI Chunying, WANG Jianru, LI Xiaohui, WANG Yongxia, GUAN Huaimin
    2024, 44 (2):  169-182. 
    doi: 10.3969/j.issn.1674-8115.2024.02.003

    Abstract ( 209 )   HTML ( 25 )   PDF (13112KB) ( 80 )  

    Objective ·To use single-cell RNA sequencing (scRNA-Seq) technology to interpret the cellular communication landscape of coronary atherosclerosis (CA), and to explore the dominant cell subsets and their key genes. Methods ·The GSE131778 data set was downloaded and preprocessed, and quality controlling, dimension reduction clustering and annotation were carried out. Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets. The FindAllMarker function was used to screen differentially expressed genes (DEGs) between the dominant cell subpopulation and other cell subpopulations, and its protein-protein interaction (PPI) network was constructed. The DEGs ranked in the top five of the Degree algorithm were taken as key genes. Then, the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs (L-R) and the signal pathways mediated by the key genes, and the results were visualized. At the same time, the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions. Results ·A total of 11 cell subsets were identified in CA lesions, including smooth muscle cells, endothelial cells, macrophages, monocytes, etc. Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets. Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication. The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets, among which ITGB2, PTPRC, CCL2, DCN and IGF1 were identified as key genes. The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway. ITGB2 formed receptor complexes withITGAM and ITGAX respectively, and then formed L-R with C3 to mediate the complement signal pathway, participating in the communication network among smooth muscle cells, macrophages and monocytes. The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis. Conclusion ·Smooth muscle cells are the dominant cells in the pathological process of CA, and have extensive communication networks with other cells. They can construct cellular communication networks with endothelial cells, macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1, C3-(ITGAM+ITGB2) and C3-(ITGAX+ITGB2).

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    Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway
    WANG Ying, PING Lifeng, LIU Tongtong, LIU Shanshan, LIU Lei
    2024, 44 (2):  183-195. 
    doi: 10.3969/j.issn.1674-8115.2024.02.004

    Abstract ( 107 )   HTML ( 18 )   PDF (5512KB) ( 82 )  

    Objective ·To investigate the effect of neferine (Nef) on renal tissues of diabetic nephropathy (DN) rats and its related mechanism. Methods ·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin, and the successfully constructed rats were randomly divided into DN group, Nef (low, medium and high) dose groups and Nef high-dose+pathway antagonist (AMD3100) group, with 10 rats in each group. At the same time, 10 common rats were selected as the normal group. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum glycosylated hemoglobin (HbA1c), serum creatinine (Scr), blood urea nitrogen (BUN) and renal index of rats in the six groups were measured. Hematoxylin-eosin (H-E) and Masson staining were used to observe the pathological changes of renal tissues. The content of malondialdehyde (MDA) in renal tissues was determined by thiobarbituric acid (TBA) method, and the activities of superoxide dismutase (SOD) and catalase (CAT) in renal tissues were determined by water soluble tetrazolium (WST-1) method and ammonium molybdate method, respectively. The mRNA and protein expressions of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in renal tissues were detected by quantitative real-time PCR (qPCR) and Western blotting, respectively. Rat renal tubular epithelium cells NRK-52E were induced by high glucose (30 mmol/L glucose) to establish DN cell model. The cells were divided into control group, high glucose (HG) group, HG+Nef (low, medium and high) dose (i.e.HG+Nef-L, M and H) group, and HG+Nef-H +AMD3100 group. SOD and CAT activities were detected by WST-1 method and ammonium molybdate method, respectively. MDA content was detected by TBA method. The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting, respectively. CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate, respecti-vely. Results ·Compared with the DN group, the levels of FBG, 24 h urinary protein, HbA1c, Scr, BUN, renal index and MDA content in Nef (low, medium and high) dose groups and Nef high-dose+AMD3100 group were decreased, the mRNA and protein expressions of SDF-1 and CXCR4 were increased, and the activities of SOD and CAT were increased (all P<0.05). The degree of pathological damage and fibrosis of renal tissues was reduced; all of the above changes were dose-dependent. AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats. Compared with the HG group, NRK-52E cell viability, SOD and CAT activities, and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L, M and H groups, while apoptosis rate and MDA content were decreased (all P<0.05). AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage. Conclusion ·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway, playing a renal protective role.

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    Clinical research
    Study on the relationship between comorbidities of chronic diseases, phase angle, and muscle mass decline related to sarcopenia in the elderly
    WANG Junlin, HAO Mingxiu, TANG Yinhan, WU Yunyun, JIN Yuhua, HU Yaomin
    2024, 44 (2):  196-203. 
    doi: 10.3969/j.issn.1674-8115.2024.02.005

    Abstract ( 75 )   HTML ( 21 )   PDF (2126KB) ( 41 )  

    Objective ·To explore the correlation between comorbidities of chronic non-communicable diseases (chronic diseases), phase angle (PhA), and muscle mass decline associated with sarcopenia in the elderly, and the predictive value of chronic disease comorbidities and PhA in muscle mass decline in the elderly. Methods ·By retrospectively screening inpatients aged ≥60 years who were admitted to the Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine from August 1, 2018 to July 31, 2019, basic information and medical history of the patients (gender, age, number of medications used, number of comorbidities, presence of osteoporosis, smoking history, etc.) were collected, as well as laboratory examination indicators (hemoglobin, albumin, serum creatinine, serum uric acid, ferritin, vitamin D, triacylglycerol, total cholesterol, high-density lipoprotein, low-density lipoprotein, etc.). The age-adjusted Charlson comorbidity index (aCCI) was calculated. The InBody S10 bioelectrical impedance body composition detector was used to test the body composition. Body mass index (BMI), skeletal muscle mass index (SMI), and PhA were collected. Some patients underwent measurement of grip strength. Muscle mass decline was diagnosed by using the SMI values recommended by the 2019 Asian Working Group for Sarcopenia (AWGS) (≤7.0 kg/m2 for males and ≤5.7 kg/m2 for females). According to the measured SMI values, patients were divided into a group with normal muscle mass and a group with muscle mass decline. Univariate and multivariate Logistic analyses were employed to investigate the risk factors associated with muscle mass decline related to sarcopenia in the elderly. Additionally, the receiver operator characteristic (ROC) curve and the area under the curve were utilized to predict the significance of these factors in muscle mass decline. Results ·A total of 359 chronic disease patients were enrolled, including 226 males and 133 females. There were 241 cases in the normal muscle mass group and 118 cases in the muscle mass decline group. The incidence of muscle mass decline related to sarcopenia in the elderly was 32.9%. The univariate Logistic regression analysis showed that age (OR=1.036, 95%CI 1.013?1.060), comorbidities (OR=1.117, 95%CI 1.025?1.217), aCCI (OR=1.123, 95%CI 1.031?1.222), and high-density lipoprotein (OR=3.688, 95%CI 2.065?6.622) were positively correlated with the risk of muscle mass decline in the elderly. BMI (OR=0.514, 95%CI 0.443?0.597), PhA (OR=0.195, 95%CI 0.126?0.303), hemoglobin (OR=0.984, 95%CI 0.972?0.996) and triacylglycerol (OR=0.606, 95%CI 0.424?0.866) were negatively correlated with the risk of muscle mass decline in the elderly. Multivariate Logistic regression model indicated that PhA (OR=0.338, 95%CI 0.119?0.959) and BMI (OR=0.634, 95%CI 0.476?0.844) were negatively correlated with the risk of muscle mass decline in elderly. The area under the ROC curve for predicting muscle mass decline related to sarcopenia in elderly by using BMI and PhA was 0.893 (95%CI 0.855?0.931) and 0.786 (95%CI 0.736?0.837), respectively. The sensitivity was 0.724 and 0.676, respectively. The specificity was 0.916 and 0.762, respectively. When BMI combined with PhA predicted muscle mass decline in the elderly, the area under the ROC curve was 0.917 (95%CI 0.883?0.951). The sensitivity was 0.867, and the specificity was 0.860. Conclusion ·aCCI is correlated with muscle mass decline associated with sarcopenia in the elderly. As BMI and PhA decrease, the risk of muscle mass decline in the elderly increases. The combination of BMI and PhA has a high predictive value in muscle mass decline in the elderly.No predictive value of chronic diseases comorbidities in muscle mass decline related to sarcopenia in the elderly is found.

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    Establishment and evaluation of nomogram for differential diagnosis of systemic lupus erythematosus based on laboratory indications
    YANG Jingyu, CHEN Liubao, WANG Kangtai, YANG Xingzhi, YU Haitao
    2024, 44 (2):  204-211. 
    doi: 10.3969/j.issn.1674-8115.2024.02.006

    Abstract ( 93 )   HTML ( 14 )   PDF (2558KB) ( 54 )  

    Objective ·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus (SLE) and other autoimmune diseases based on laboratory indications, and to evaluate its efficacy. Methods ·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group, and 535 patients with other autoimmune diseases during the same period were selected as control group. Basic information and laboratory test indicators of the SLE group and control group were collected and compared. The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3, respectively. LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE. The nomogram for differential diagnosis of early SLE (SLE nomogram) was established according to the selected main risk factors. Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram. The receiver operator characteristic curve (ROC curve) and decision curve analysis (DCA) were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram, respectively. The "DynNom" package of R language was used to convert the nomogram into an electronic calculator, and its consistency with SLE nomogram was verified by data from 3 groups of patients. Results ·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE, including antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, anti-ribonucleoprotein antibody/anti-Simth antibody (anti-nRNP/Sm), anti-ribosomal P protein (anti-P) antibody, anti-nucleosome antibody (ANuA) and urinary protein (PRO), which were used to construct the SLE nomogram. The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set, respectively, and its area under the curve (AUC) was 0.889 and 0.869, respectively. The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95, the model achieved more net benefit. The prediction results of the electronic calculator showed that when ANA (titer 1∶100) was positive in SLE patient No.1, the prevalence was 0.166; when both ANA (titer 1∶100) and ANuA (titer 1∶100) were positive in patient No.2, the prevalence was 0.676; when all of PRO, ANA (titer 1∶100), ANuA (titer 1∶100) and anti-P antibody (titer 1∶100) were positive in patient No.3, the prevalence was 0.990, which was consistent with the differential diagnosis results of the SLE nomogram. Conclusion ·The established SLE nomogram based on ANA, anti-dsDNA antibody, anti-nRNP/Sm, anti-P antibody, ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases, and have important clinical application value.

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    Study of metabolic association between elevated fasting blood glucose and cognitive deterioration
    WU Lirong, CHEN Ruihua, CHAO Xiaowen, GUO Yuhuai, SUN Tao, LI Mengci, CHEN Tianlu
    2024, 44 (2):  212-222. 
    doi: 10.3969/j.issn.1674-8115.2024.02.007

    Abstract ( 93 )   HTML ( 22 )   PDF (2309KB) ( 53 )  

    Objective ·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose (FBG) and the metabolic clues associated with changes in the risk of cognitive deterioration. Methods ·Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were downloaded, and the samples with FBG and follow-up data were selected from the database. Clinical information, including age, gender, body mass index, education years,apolipoprotein E4 (APOE4) genotype and race, and corresponding metabolic indicator data, including amino acids, fatty acids, proteins and others were obtained. Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease, the subjects were categorized into four groups: normal FBG without/with cognitive deterioration, and elevated FBG without/with cognitive deterioration. The univariate analysis method, the Cox proportional hazards model, orthogonal projections to latent structures discriminant analysis (OPLSDA), and Spearman correlation analysis were employed for data analysis. Results ·A total of 1 317 subjects were included, among which 1 153 had normal FBG level (>3.9 mmol/L and <6.1 mmol/L) and 164 had elevated FBG level (≥6.1 mmol/L). In the normal FBG group, 275 subjects showed cognitive deterioration, while in the elevated FBG group, 53 subjects showed cognitive deterioration. Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group, and significant differences in age, gender, and APOE4 genotype between the groups with and without cognitive deterioration (all P<0.05). Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity, elevated FBG, and increasing age in order (HR=2.22,HR=1.38,HR=1.02; all P<0.05). In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration, as well as metabolic indicators before and after cognitive deterioration at different FBG levels, the results of the analysis of variance revealed that in the cognitively deteriorated population, the ratio of phospholipids carried by high-density lipoproteins (HDL) to total lipids was significantly higher; low-density lipoprotein (LDL) particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration. Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau (pTau) level in the plasma in the cognitively deteriorated population. Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid (CSF). Conclusion ·Compared to the individuals with normal FBG level, those with high FBG level have a significantly higher risk of cognitive deterioration. Additionally, different metabolic indicators show significant differences between the groups without and with cognitive deterioration, as well as metabolic indicators before and after cognitive deterioration at different FBG levels. Overall, LDL and its lipid content, and HDL-carried phospholipids show an increasing trend during cognitive deterioration, and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma, suggesting that these metabolic markers may play an important role in cognitive deterioration.

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    Efficacy and safety of hypertonic dextrose prolotherapy for patients with post-herpetic neuralgia
    YIN Qin, CHEN Liping, XU Heng, YUAN Yan, LIANG Dong, SHEN Wen
    2024, 44 (2):  223-227. 
    doi: 10.3969/j.issn.1674-8115.2024.02.008

    Abstract ( 73 )   HTML ( 16 )   PDF (1327KB) ( 36 )  

    Objective ·To investigate the efficacy and safety of hypertonic dextrose prolotherapy (DPT) in the treatment of postherpetic neuralgia. Methods ·Seventy-eight patients with postherpetic neuralgia who visited the Department of Pain of The Affiliated Hospital of Xuzhou Medical University from June 2019 to December 2022 were selected. The patients were randomly assigned to a control group and a research group in a 1∶1 ratio, with 39 patients in each group. The control group was treated with traditional analgesic solution, while the research group was treated with traditional analgesic solution combined with DPT. Visual analog scale (VAS) was used to evaluate the patients' pain level before and after treatment, flow cytometry was used to measure the patients' T-cell subsets, and enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and IL-10 cytokines. The VAS scores were compared between the two groups of patients before and at 1, 2, 4, 8, and 12 weeks after treatment. CD4+/CD8+, CRP, IL-6, IL-10 levels, and the incidence of adverse reactions before and 2 weeks after treatment were compared between the two groups. Results ·There was no statistically significant difference in sex ratio, age, and disease duration between the two groups of patients. The VAS scores of the two groups of patients at 1, 2, 4, 8, and 12 weeks after treatment were significantly lower than those before treatment, and the differences were statistically significant (all P<0.05). The VAS scores of the research group at 1, 2, 4, 8, and 12 weeks after treatment were significantly lower than those of the control group (all P<0.05). There was no statistically significant difference in basal CD4+/CD8+, CRP, IL-6 and IL-10 levels between the two groups of patients. IL-6 and CRP levels in the research group were significantly lower after treatment than those in the control group, and the differences were statistically significant (all P=0.000). CD4+/CD8+ and IL-10 levels were significantly higher in the research group than those in the control group after treatment, and the difference was statistically significant (all P=0.000). No adverse reactions such as local nerve damage, epidural hematoma, infection, pneumothorax or allergy occurred in both groups of patients during the treatment. Conclusion ·DPT can significantly reduce the pain of PHN patients, improve patients' T lymphocyte subpopulations and cytokine expression, and can be safely applied to the clinic.

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    Application of continuous nursing based on EMS management mode in preschool children with wheezing diseases
    JIANG Yunli, LI Aiqiu, XIAO Yanshang, LI Tiantian, HU Yachen, ZHANG Xiaoxiao, WU Beirong
    2024, 44 (2):  228-236. 
    doi: 10.3969/j.issn.1674-8115.2024.02.009

    Abstract ( 84 )   HTML ( 17 )   PDF (1423KB) ( 61 )  

    Objective ·To explore the effect of continuous nursing based on EMS [environment management (E), medicine direction (M) and self monitoring (S)] management mode on the preschool children with asthmatic diseases. Methods ·A total of 67 children aged 0 to 6 years with asthmatic diseases admitted to the Department of Respiratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine from December 2019 to November 2020 were selected and divided into observation group (33 cases) and control group (34 cases) according to the random number table method, with 3 cases lost, and finally 32 cases in each group. The observation group received continuous nursing care based on EMS management mode, while the control group received routine care and discharge follow-up through the telephone. The children in the two groups were followed up at 1, 3, and 6 months after discharge to evaluate the results of Test for Respiratory and Asthma Control in Kids (TRACK) and wheezing recurrence; Medication Adherence Report Scale for Asthma (MARS-A) and Nursing Job Satisfaction Questionnaire were used to evaluate medication adherence and nursing job satisfaction 6 months after discharge. Results ·There was no significant difference in demographic characteristics and clinical baseline characteristics between the two groups. Repeated measures analysis of variance showed that effects of time, groups and the interaction of groups×time on the total score of TRACK were statistically significant. The total scores of TRACK in the observation group were significantly higher than those in the control group at 1, 3, and 6 months after discharge (P=0.000). The total scores of TRACK in the two groups gradually increased with time (P=0.000). The recurrence rates of wheezing in the observation group were 25.0%, 18.7%, and 9.4% at 1, 3, and 6 months after discharge, which were significantly lower than those in the control group (50.0%, 43.7%, and 31.3%, respectively, P<0.05). Generalized estimating equation analysis showed that there was a statistically significant difference between the two groups (P=0.013), and the intervention effect of the observation group was better than that of the control group (OR=0.292). The MARS-A score of the observation group was 4.519±0.395 at 6 months after discharge, which was significantly higher than that of the control group (3.994±0.739, P=0.001). The nursing job satisfaction of the observation group was significantly higher than that of the control group (P=0.000). There was a moderate positive correlation between the MARS-A score and the nursing job satisfaction (r=0.389, P=0.001). Conclusion ·Continuous nursing based on EMS management mode can significantly improve the medication compliance and wheezing control level of the preschool children with asthmatic diseases, significantly reduce the recurrence rate of wheezing, and improve the nursing satisfaction.

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    Evidence-based medicine
    Quality assessment of global obstructive sleep apnea guidelines
    GAO Yiqing, PENG Yu, XU Huajun, YI Hongliang, GUAN Jian, YIN Shankai
    2024, 44 (2):  237-249. 
    doi: 10.3969/j.issn.1674-8115.2024.02.010

    Abstract ( 95 )   HTML ( 20 )   PDF (1982KB) ( 59 )  

    Objective ·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea (OSA) published worldwide. Methods ·The guidelines of OSA were retrieved in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, SinoMed, MedSci, The Cochrane Library, and the websites such as Medlive, U. S. Preventive Services Task Force (USPSTF), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Scottish Intercollegiate Guidelines Network (SIGN), and Guidelines International Network (GIN) from establishment to December 2022. Two reviewers screened the literature and extracted the main information independently, using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) to evaluate the quality of the included OSA guidelines. Subgroup analysis was performed according to the publication regions of guidelines. The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient (ICC). All the included guidelines were read entirely and the clinical questions they raised were summarized. Results ·A total of 35 OSA guidelines were included. The ICC value of 0.975 showed a good inter-evaluator agreement. The results of AGREE Ⅱ showed that the average score of all guidelines was (63.60±16.45)%, with a minimum of 23.40% and a maximum of 91.67%. In the six domains, the scores of "Rigor of development" [(56.07±25.89)%] and "Applicability" [(53.57±15.52)%] were relative low. The average reporting rate of RIGHT of all the included guidelines was (67.84±20.03)%, with a minimum of 14.29% and a maximum of 94.29%, and the three domains with the lowest reporting rates were "Review and quality assurance" [(31.40±45.51)%], "Funding and conflict of interest declaration and management" [(56.43±33.95)%] and "Other aspects" [(56.19±36.85)%]. Subgroup analysis showed that guidelines in Asian had a lower score in "Rigor of development" and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe (both P<0.05), and the reporting rates in the domains of "Evidence" and "Other information" of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe (P<0.05). These guidelines focused on 42 clinical questions which were classified to 3 aspects, i.e. screening and diagnosis, treatment and long-term management of OSA. Conclusion ·The quality of current global OSA guidelines varies a lot, and they need to be strengthened in terms of rigor of development, applicability, review and quality assurance, funding and conflict of interest declaration and management, especially those in Asia.

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    Public health
    Association between body mass index and chronic metabolic diseases in Chinese aged population
    JIANG Ying, LI Qingyao, CHEN Zhiqi, WANG Jialu, LI Yun, XU Renying
    2024, 44 (2):  250-257. 
    doi: 10.3969/j.issn.1674-8115.2024.02.011

    Abstract ( 63 )   HTML ( 19 )   PDF (1681KB) ( 60 )  

    Objective ·To evaluate the relationship between body mass index (BMI) and chronic metabolic diseases. Methods ·The elderly (≥60 years old) who were underwent physical examination in the Physical Examination Center of Renji Hospital, Shanghai Jiao Tong University School of Medicine from 2014 to 2021 were studied. Their results of biochemical indicators were collected. Their height, body weight, and blood pressure were measured by trained nurses. The history of chronic metabolic diseases was collected by self-reported questionnaire. Systolic blood pressure ≥140 mmHg (1 mmHg=0.133 kPa), diastolic blood pressure ≥90 mmHg, or self-reported hypertension history was defined as hypertension. Fasting blood glucose ≥7.0 mmol/L or self-reported history of diabetes was defined as diabetes. Total cholesterol≥6.2 mmol/L, triglyceride≥2.3 mmol/L, or self-reported history of dyslipidemia was defined as dyslipidemia. The relationship between BMI and hypertension, diabetes, and dyslipidemia was evaluated by using receiver operator characteristic (ROC) curve analysis and binary logistic regression. Results ·Data of 59 083 subjects were collected [30 807 men and 28 276 women, average age: (67.9±6.3) years old]. The prevalence of hypertension, diabetes and dyslipidemia was 76.5% (45 219/59 083), 24.1% (14 225/59 083) and 50.0% (29 544/59 083), respectively. Compared to the elderly people aged 60?74 years, those aged 75 years and above had a higher proportion of hypertension and diabetes, and a lower proportion of dyslipidemia and no metabolic abnormalities. With ROC analysis, the BMI cut-off values for hypertension, diabetes, and dyslipidemia were 24.3, 23.9, and 23.9 kg/m2. The BMI cut-off values for hypertension and diabetes in elderly men were similar to those in elderly women (for hypertension: 24.3 kg/m2 in elderly men vs 24.2 kg/m2 in elderly women; for diabetes: 24.0 kg/m2 in elderly men vs 23.7 kg/m2 in elderly women); however, BMI cut-off value for dyslipidemia was obviously higher in elderly men than that in elderly women (24.0 kg/m2 in elderly men vs 22.5 kg/m2 in elderly women). The BMI cut-off value for chronic metabolic diseases was higher in the elderly people aged 60?74 years than that in the elderly people aged 75 years and above (24.2?24.7 kg/m2vs 22.9?23.8 kg/m2). Conclusion ·Elderly people aged 60?74 years should maintain the BMI below 24.0 kg/m2, while those aged 75 years and above should aim for the BMI below 23.0 kg/m2, so as to reduce the risk of chronic metabolic diseases.

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    Review
    Research progress of neuromodulation in the treatment of Parkinson's disease
    HU Canfang, ZHONG Chuanyu, CAO Li
    2024, 44 (2):  258-263. 
    doi: 10.3969/j.issn.1674-8115.2024.02.012

    Abstract ( 146 )   HTML ( 28 )   PDF (1216KB) ( 152 )  

    Parkinson's disease (PD) is a common degenerative neurological disorder, characterized by static tremor, bradykinesia, myotonia and postural abnormalities. Dopaminergic drugs are the main drugs in the treatment of PD, but long-term use will lead to drug efficacy loss, and even cause some adverse reactions such as dyskinesia and "on-off" phenomenon. Neuromodulation is a kind of biomedical engineering technology that can stimulate or inhibit the activity of brain neurons and regulate the changes of neuroplasticity by means of electric energy, magnetic field, ultrasound and other methods, so as to achieve treatment and improvement of diseases. In the non-drug treatment of PD, neuromodulation, as a new therapeutic means, has shown good efficacy, and has the advantages of small adverse reactions and easy tolerance. Based on this, this article reviews the research progress of several common neuromodulation in PD, including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation and transcranial focused ultrasound.

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    Research progress in targeted therapies of chronic lymphocytic leukemia
    DING Yanling, LI Jie, YUAN Jun, LI Yan
    2024, 44 (2):  264-270. 
    doi: 10.3969/j.issn.1674-8115.2024.02.013

    Abstract ( 131 )   HTML ( 24 )   PDF (1329KB) ( 65 )  

    Chronic lymphocytic leukemia (CLL) is one of small B-cell lymphomas and leukemias, characterized as a clonal disease of mature B cells. The disease is remarkably heterogeneous, with the majority of patients having an indolent course, yet they are currently incurable. Abnormal signaling pathways are indispensable in the pathogenesis of CLL. In CLL, the common abnormalities of signaling pathways include B-cell receptor (BCR) signaling, apoptosis, nuclear factor kappa B (NF-κB) signaling and Notch signaling. According to the target in signaling pathways, a series of targeted drugs, such as Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, zanubrutinib), phosphorylate phosphoinositide 3-kinase (PI3K) inhibitor (duvelisib) and B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax), which have significantly changed the prognosis of patients in clinic. Other targeted drugs, such as fenebrutinib, nemtabrutinib and umbralisib, as well as chimeric antigen receptor T-cell (CAR-T) therapy developed in the field of immuno-oncology and T cell engineering, are currently under trial, with more personalized treatment modalities being explored, which may become potential drug targets in the future. In this paper, relevant literature of CLL was reviewed, and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

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    Progress of research on m6A demethylases in gastric cancer
    JIANG Shuang, YU Jiwei
    2024, 44 (2):  271-277. 
    doi: 10.3969/j.issn.1674-8115.2024.02.014

    Abstract ( 55 )   HTML ( 23 )   PDF (1293KB) ( 34 )  

    Gastric cancer (GC) is one of the most common malignancies in the digestive system. Many patients are found in advanced stage and have a poor prognosis. Surgery and chemotherapy remain the main treatments for gastric cancer. N6-methyladenosine (m6A) is a hot topic in tumor research in recent years. As the most common form of RNA modification in eukaryotes, m6A can regulate various stages of the RNA cycle, including RNA splicing, processing, degradation, and translation, thereby regulating RNA expression and function, playing a critical role in various pathways such as cell differentiation, development, and metabolism. The m6A demethylase can remove methyl groups on RNA, ensuring that m6A methylation is a dynamic and reversible process. As a key enzyme in the m6A methylation process, the imbalance of m6A demethylases fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and ALKBH3 regulate the progression of gastric cancer through various mechanisms, which is closely related to the occurrence and development of gastric cancer. These m6A demethylases regulate the signaling pathway, alter the proliferation and invasion ability of gastric cancer cells, affect its resistance to chemotherapy drugs, participate in regulating the immune response and mitochondrial metabolism of gastric cancer, and affect the growth of gastric cancer cells. They are expected to become a novel therapeutic target. This article comprehensively summarizes the molecular mechanism of m6A demethylase involved in the occurrence and development of gastric cancer, and the relationship between its expression and function, and biological characteristics of m6A demethylase were reviewed, aiming to provide new research ideas for early diagnosis and targeted treatment of gastric cancer.

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    Case report
    Systemic lupus erythematosus complicated with pure red cell aplasia: a case report and literature review
    CHEN Qiong, FANG Jie, WEI Qianghua
    2024, 44 (2):  278-286. 
    doi: 10.3969/j.issn.1674-8115.2024.02.015

    Abstract ( 84 )   HTML ( 21 )   PDF (1933KB) ( 45 )  

    This article reports a single case of a patient with systemic lupus erythematosus (SLE) combined with pure red cell aplasia (PRCA), and reviews 51 additional cases of patients reported by domestic and overseas papers from 1974 to 2021. These 52 (51+1) cases were analyzed to summarize the epidemiological features, clinical features, laboratory inspections, treatments and prognosis of the patients. The results indicated that among all the 52 cases, cases of SLE combined with PRCA were mostly seen in Asian childbearing age women. The median ages of patients diagnosed with SLE and diagnosed with PRCA were 31.5 years and 36.0 years, respectively. The time interval between the initial diagnosis of SLE and subsequent diagnosis of PRCA was significantly longer than the interval for the initial diagnosis of PRCA, suggesting a delayed onset of SLE in these patients (P=0.042). Various clinical features of the 52 patients were reported, including mostly fatigue, joint pains, Raynaud phenomena and rashes, and SLE maybe combined with autoimmune hemolytic anemia (AIHA), thymoma, hypothyroidism and myasthenia gravis (MG). In these reported cases, laboratory indicators showed higher proportions of antinuclear antibody (ANA), anti double stranded DNA antibody (anti-dsDNA antibody), positive urinary protein and low complement levels. Among the 52 patients, 51 cases (98.08%) were treated with glucocorticoids, followed by blood transfusion, cyclosporin A, cyclophosphamide and high-dose intravenous immunoglobulin. Of the 50 patients whose prognoses were reported, 44 showed improvement, while 3 treatments were not effective and 3 resulted in death. This article aims to enhance the understanding of SLE combined with PRCA among doctors.

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    A case of chronic myelomonocytic leukemia complicated with immune thrombocytopenia
    LIU Jiayu, HUANG Fang, HAO Siguo
    2024, 44 (2):  287-290. 
    doi: 10.3969/j.issn.1674-8115.2024.02.016

    Abstract ( 57 )   HTML ( 14 )   PDF (1253KB) ( 39 )  

    Chronic myelomonocytic leukemia (CMML) complicated with immune thrombocytopenia (ITP) is rare. This article reports the clinical data of a patient with CMML complicated with ITP treated with a combination of venetoclax, ripertamab (an anti-CD20 monoclonal antibody), and hetrombopag. The coexistence mechanism of CMML and ITP needs to be further clarified. Venetoclax combined with anti-CD20 monoclonal antibody and thrombopoietin receptor agonist may be an effective strategy for the treatment of this complication.

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