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10 January 2024, Volume 40 Issue 1
Symposiums
Progress of electromagnetic navigation bronchoscopy in diagnosis and treatment of pulmonary nodules
Xi′nan CHEN,Xudong. XU
2024, 40(1):  1-6.  doi:10.3969/j.issn.1006-5725.2024.01.001
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With the popularity of low?dose computed tomography (LDCT) in physical examination and the widespread concern of people about lung diseases after COVID?19 outbreak, the detection rate of pulmonary nodules in the population has increased year by year. The clinical cases of early lung cancer and multiple primary lung cancer are increasing, and the necessity of personalized treatment tailored to the diverse detection of pulmonary nodules is highlighted in the diagnosis and treatment process of pulmonary nodules. However, chest CT and traditional bronchoscopy not only have insufficient accuracy in preoperative localization of pulmonary nodules and the diagnosis of benign and malignant pulmonary nodules, but also have significant limitations in the diagnosis and treatment of patients who cannot undergo surgery. The emergence of electromagnetic navigation bronchoscopy (ENB) has greatly solved this problem and further improves the diagnosis and treatment process of pulmonary nodules. ENB is a new technology that relies on electromagnetic positioning technology to locate, biopsy, and minimally invasive treatment of pulmonary nodules through bronchoscopy. In this review, we mainly summarize the application and latest progress of ENB in the diagnosis and treatment of pulmonary nodules.

Feature Reports:Lung cancer
RNA sequencing⁃based research on the immune regulation mechanism of C⁃MET in lung cancer
Yue XU,Yanbin ZHANG,Shan. SU
2024, 40(1):  7-12.  doi:10.3969/j.issn.1006-5725.2024.01.002
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Objective To analyze the immune regulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology. Methods The C-MET expression of lung adenocarcinoma cell line (H1993) and lung squamous cell carcinoma cell line (EBC-1) with high C-MET expression was silenced using siRNA molecular interference technology. The differentially expressed genes (DEGs) before and after C-MET silencing were detected using transcriptome sequencing technology. The signal pathways and related genes of the immune microenvironment in which C-MET may participate in regulation were excavated through bioinformatics analysis. Finally, the co-culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on immune factors such as INF-γ, INF-β and CXCL-10. Results We detected 505 DEGs in total using transcriptome sequencing.There were 38 differentially expressed genes in the C-MET regulation group before and after H1993, 24 upregulated differentially expressed genes, and 14 downregulated differentially expressed genes, respectively. There are a total of 467 differentially expressed genes in the C-MET regulation group of EBC-1, 347 upregulated differentially expressed genes, and 121 downregulated differentially expressed genes, respectively. KEGG analysis of differential genes suggested that C-MET expression might participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway, white blood cell differentiation, cytokine receptor activity, cell cycle, cytokine receptor activity, and cytokine-cytokine receptor interaction. The effect of C-MET on immune factor secretion was verified using the co-culture technique of lung cancer cells and human immune cells, and the results of Rt-qPCR assay suggested,the mRNA transcriptional level of INF-γ in PBMC co-cultured with the C-MET high expression group was 77 times that of the low expression group, and the mRNA transcriptional level of CXCL-10 was 1.6 times that of the low expression group. The mRNA transcriptional level of INF--β was twice as high as that of the low expression group. Conclusion C-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway, leukocyte differentiation, and cytokine receptor activity pathway.

Role and potential mechanisms of p62/SQSTM1 on migration and metastasis of non⁃small cell lung cancer
Xue MA,Shihui. ZHOU
2024, 40(1):  13-18.  doi:10.3969/j.issn.1006-5725.2024.01.003
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Objective To investigate the effect and regulatory mechanism of autophagy related multifunctional protein p62/SQSTM1 on biological behavior in non?small cell lung cancer (NSCLC). Methods RT?qPCR was used to detect the expression of p62 in normal lung cells and NSCLC cells. CCK?8, wound?healing and Transwell assays were used to detect the effects of inhibition and promotion of p62 expression on the proliferation, migration and invasion in NSCLC cells. Western blotting was used to detect the effects of inhibition and promotion of p62 expression on the expression of apoptosis?related proteins (Bcl?2 and Bax) and autophagy?related proteins (ATG5 and Becline1) in NSCLC cells. A nude mouse transplantation tumor experiment was used to detect the effect of inhibiting p62 expression on the tumor volume and mass of NSCLC cells in vivo. Results Compared with that in normal lung cells, the expression level of p62 in A549 cells was the highest. Cell function experiments in vitro showed that inhibition of p62 expression reduced the abilities of proliferation, migration and invasion in A549 cells, and suppressed autophagy and induced apoptosis. Consistently, p62 overexpression has the opposite effects. In addition, animal experiments in vivo showed that inhibition of p62 expression decreased the tumor volume and mass of tumor?bearing mice. Conclusion p62 could promote the growth of NSCLC A549 cell in vivo and in vitro by modulating autophagy.

The mechanism of lipid metabolism disorders promoting progression of lung cancer based on the oxLDL/LOX⁃1 signaling pathway
Yang WU,Jian YAO,Jinliang. CHEN
2024, 40(1):  19-24.  doi:10.3969/j.issn.1006-5725.2024.01.004
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Objective To explore the mechanism of lipid metabolism disorder promoting the progress of lung cancer based on the oxidized low density lipoprotein (ox?LDL)/ human lectin?like oxidized low density lipoprotein receptor 1(LOX?1) signaling pathway. Methods Eighty?one identified lung adenocarcinoma tissues with paired adjacent non?cancerous tissues (at least 5 cm away from the tumor) were collected from our hospital, and the expression of LOX?1 was detected by immunohistochemistry. LOX?1 was overexpressed in lung adenocarcinoma cell lines (A549 and H1299 cells). Cell invasion ability was measured by Transwell. Cells were treated with different concentrations of oxLDL, and cellular LOX?1 expression was investigated. Results LOX?1 staining in the tumor was significantly stronger than that in the non?cancerous tissue samples (99.4 vs. 16.2 for median H score, P < 0.001). High LOX?1 expression was significantly correlated with low survival (P < 0.001). As compared with the patients without lymph node metastasis, those with lymph node metastasis had higher LOX?1 level (83.2 vs. 121.1 for median H score, P < 0.01). Overexpression of LOX?1 in lung cancer cells significantly promoted the number of invasive and metastatic cells (P < 0.01). In addition, LOX?1 was an essential functional target for oxLDL?induced metastasis of lung cancer cells. Itatinib inhibited the metastasis of LOX?1 overexpressed A549 in vitro. Conclusions With an increase in oxLDL level, the expression of LOX?1 increases. Up?regulation of LOX?1 promotes metastasis of lung cancer, and its mechanism may be related to activation of the JAK1/STAT6 signaling pathway.

Effect of the KLF14⁃mediated JAK⁃STAT signaling pathway on prognosis of lung cancer
Peng WANG,Sumei YAO,Xuedong LV,Jinliang. CHEN
2024, 40(1):  25-31.  doi:10.3969/j.issn.1006-5725.2024.01.005
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Objective To investigate the influence of the Janus kinase?signal transducer and transcription activator (JAK?STAT) signaling pathway mediated by Kruppel?like factor 14 (KLF14) on the prognosis of non?small cell lung cancer (NSCLC). Methods From January 2018 to September 2019, NSCLC tissues from 80 patients and malignancy?free paracancerous tissues from 25 patients were collected. Medical follow?up ended in April 2023. Immunohistochemistry was used to detect the expression of KLF14 in tissues, and the patients were divided into a high?expression group and a low?expression group according to the median level of KLF14 expression. Over?expression or knock?down of KLF14 and JAK1 was achieved by transfection of KLF14 and JAK1 overexpression plasmid in A549 cells and transfection of KLF14 and JAK1 specific short hairpin RNA (shKLF14 and shJAK1) in HCC827 cells. The proliferation activity of cells was analyzed by cell clone formation test. Transwell analyzed the migration and invasion of cells. Results As compared with the normal paracancerous tissues, the expression of KLF14 in NSCLC tissue decreased (P < 0.001). The low expression of KLF14 was significantly correlated with tumor diameter of > 3 cm, lymph node metastasis and clinical stage Ⅲ (P < 0.05). There was a significant difference in the overall survival rate between the high KLF14 expression group and the low KLF14 expression group, and the patients with low KLF14 expression had poor prognosis (P = 0.039). After overexpression of KLF14, the proliferation ability of A549 cells and the number of migration and invasion of these cells decreased significantly (P < 0.05); while after knock?down of KLF14, the proliferation ability of HCC827 cells and the number of migration, and invasion of these cells increased significantly (P < 0.05). As compared with Vector + KLF14 group, the number of colonies, migration and invasion of A549 cells in JAK1 + KLF14 group increased significantly (P < 0.05). As compared with shNC + shKLF14 group, the number of colonies, migration and invasion of HCC827 cells in shJAK1 + shKLF14 group decreased significantly (P < 0.05). Conclusions Low expression of KLF14 is associated with poor overall survival in NSCLC patients. Up?regulation of KLF14 significantly inhibits the proliferation and metastasis of lung cancer cells in vitro, and its mechanism may be related to inhibition of the JAK?STAT signaling pathway.

Clinical efficacy of CalliSpheres drug⁃loaded microspheres versus blank microspheres in the treatment of advanced non⁃small cell lung cancer by transarterial chemoembolization
Ruiwen CHENG,Ruobing HAO,Ping LI,Kun ZHANG,Liping DENG,Yaheng CAO,Lin SU,Hongrong. SHEN
2024, 40(1):  32-37.  doi:10.3969/j.issn.1006-5725.2024.01.006
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Objective To analyze and compare the clinical efficacy of CalliSpheres drug-eluting microspheres and blank microspheres in the treatment of advanced non-small cell lung cancer by bronchial arterial chemoembolization. Methods Fifty patients with advanced non-small cell lung cancer who had failed or relapsed after radiotherapy, chemotherapy, targeting and immunotherapy were collected and treated with super-selective bronchial artery chemoembolization. A retrospective analysis was conducted to compare the tumor response rate and survival between CalliSpheres drug-eluting and blank microspheres. Results The PR, ORR and DCR in the drug-eluted microsphere group were higher than those in the blank microsphere group, and there was a statistical difference in DCR between the two groups 1 month after surgery (χ2 = 4.08, P = 0.04). PD in the drug-eluted microsphere group was lower than that in the blank microsphere group. The CEA, CYF and SCC in the drug-eluted microsphere group after surgery were lower than those in the blank microsphere group, and the CEA, CYF and SCC in the two groups after surgery were lower than those before surgery, and there were statistical differences in CEA and CYF 1 month after surgery between the two groups. The PFS and OS in drug-eluted microsphere group were higher than those in blank microsphere group. Conclusion CalliSpheres drug-eluting microspheres could improve the effective rate of tumor treatment and prolong the survival time more effectively than the blank microspheres via arterial chemoembolization, providing reliable clinical practice basis for the treatment of advanced non-small cell lung cancer.

Analysis of common driver gene mutations in 661 cases of non⁃small cell lung cancer in eastern region of Henan Province
Yan WANG,Yajing HE,Lina HUANG,Yuwen. ZHANG
2024, 40(1):  38-42.  doi:10.3969/j.issn.1006-5725.2024.01.007
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Objective To analyze the mutation of common driver genes in patients with non?small cell lung cancer (NSCLC) in eastern Henan Province. Methods A retrospective analysis was performed on 661 patients with NSCLC admitted to the First People's Hospital of Shangqiu city from March 2022 to July 2023. Five kinds of gene mutation detection kits (fluorescent PCR) were used for gene detection in all enrolled patients. The relationship between the clinical features and the status of each driver gene was analyzed by statistical methods. Results In the 661 patients with NSCLC, the mutation rates of EGFR, KRAS, ALK, ROS1, PIK3CA, BRAF, HER2, RET, MET14 and NRAS were 47.35%, 9.68%, 5.45%, 1.82%, 2.87%, 1.82%, 1.21%, 0.91%, 0.61% and 0%. Mutations in EGFR, ROS1 and HER2 were more likely to occur in women (P < 0.05), while KRAS mutations were more common in men (P < 0.05). The mutation rates of EGFR, KRAS and ALK in adenocarcinoma was significantly higher than that in squamous cell carcinoma and NSCLC. NOS (P < 0.05), and the mutation rate of PIK3CA in NSCLC.NOS was the highest. The mutation rate of KRAS gene in stage Ⅰ+Ⅱ was significantly higher than that in stage Ⅲ+Ⅳ (P < 0.05), and there was no significant correlation between other genes and clinical stage. Compared with smokers, the mutation rate of total driver gene was significantly higher in non?smokers (P < 0.05). EGFR, ALK, PIK3CA, ROS1, BRAF and HER2 were more common in non?smokers (P < 0.05), while KRAS gene was more common in smokers (P < 0.05). The mutation rate of 10 driver genes in sediment cell block samples was 78.67%, and the detection rate was significantly higher than that in other types of samples (P < 0.05). Conclusion Common driver genes such as EGFR, KRAS and ALK are correlated with gender, pathological type, clinical stage and smoking. Qualified samples of sediment cells have obvious advantages for gene detection and could be widely promoted in patients. ARMS?PCR combined detection of 10 genes could be used as the preferred gene detection method for newly diagnosed and treated NSCLC patients.

An analysis on clinical characteristics in patients with lung adenocarcinomas tested positive for EGFR mutation in pleural effusion
Ying LIU,Yun LIU,Jiahui LIU,Lu WANG,Wenrui HOU,Xiaoli LI,Junxin XIANG,Dianming. LI
2024, 40(1):  43-47.  doi:10.3969/j.issn.1006-5725.2024.01.008
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Objective To analyze the clinical characteristics of lung adenocarcinoma patients with positive EGFR mutations detected in pleural effusion. Methods We retrospectively analyzed the clinical characteristics including gender, age, smoking history, presence of other underlying diseases (such as COPD, cardiovascular disease, and diabetes), site of pleural fluid, feature of pleural fluid, and TNM stage in patients with lung adenocarcinoma who had been admitted to the first Affiliated Hospital of Bengbu Medical College from 2020.01 to 2022.12 for the first time by the detection of EGFR mutation positive in pleural effusion. The data were statistically analyzed using the SPSS 26.0 software. Results A total of 126 patients were screened for enrollment, including 61 patients (48.41%) with EGFR exon 19 deletion mutation (19del), 56 patients (44.44%) with exon 21 L858R mutation (21L858R), and 9 patients (7.14%) with non?classical mutations. Univariate analysis showed that the three mutation subtypes were statistically significant in terms of gender, age, smoking history, and presence of COPD (P < 0.05 for all comparisons), but not in terms of pleural fluid site, feature of pleural fluid, tumor size, and presence of cardiovascular disease, diabetes mellitus, presence of distant metastases, and mediastinal lymph node metastases (P > 0.05 for all comparisons); Multivariate analysis showed that 21 L858R mutation was more likely to be found in male, older age, non?smoking, and presence of COPD than 19del mutation; non?classical mutation was more likely to be found in male than 19del mutation. Conclusions There are significant differences among the three mutation subtypes in sex, age, smoking history, and presence of COPD, but not in pleural fluid location, feature of pleural fluid, tumor size, presence of cardiovascular disease or diabetes mellitus, presence of distant metastases, or mediastinal lymph node metastases; Among lung adenocarcinoma patients with positive EGFR mutations in pleural fluid, 21 L858R mutation mostly occurs in male, older age, non?smokers, and those complicated with COPD, while non?classical mutation mainly develops in male. However, more case studies are needed to confirm the above conclusions.

Clinical significance of detection of EGFR mutation in alveolar lavage fluid exosome of patients with advanced non⁃small cell lung cancer
Changheng YANG,Ying CHEN,Zhongyuan ZHANG,Qingqing. MA
2024, 40(1):  48-52.  doi:10.3969/j.issn.1006-5725.2024.01.009
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Objective To compare and analyze the gene mutation of EGFR of bronchoalveolar lavage fluid (BALF) exosome, serum and lung cancer tissue specimens of patients with advanced non?small cell lung cancer (NSCLC) and assess whether the BALF exosome specimens are suitable for screening before clinical targeted therapy, to provide new ideas and screening methods for early individualized treatment of advanced NSCLC patients. Methods BALF exosomes, serum and lung cancer tissue specimens EGFR gene mutations of 78 cases with advanced NSCLC were detected by using amplification refractory mutation system(ARMS) method in Department of Respiratory and Critical Care Medicine in our hospital from May 2021 to May 2023, and the results were retrospectively analyzed. A comparative analysis of the specimens was conducted using lung cancer tissue specimens as benchmarks. Results A total of 33, 25 and 38 cases of EGFR gene mutation and 42, 53 and 40 cases of EGFR wild type were detected in BALF exosomes, serum and lung cancer tissues specimens respectively. The mutation rate of EGFR gene was 42.3%(33/78, 32.1 %(25/78)and 48.7%(38/78)in BALF exosomes, serum and lung cancer tissues specimens respectively. EGFR detection showed no results in 3 cases and the false?negative rate was 6.4% (5/78) in BALF specimen, and false?negative rate was 16.7% (13/78) in serum. The detection coincidence rate of EGFR mutation was 86.8% (33/38) in BALF exosomes specimen, and 65.8% (25/38) in serum. Conclusions EGFR gene mutation rate in BALF exosome specimen is consistent with that in serum and lung cancer tissue samples, showing no statistical significance (P > 0.05). It is superior to serum specimen and suitable for patient screening before targeted therapy and provides new ideas and screening methods for early individualized treatment decisions of advanced NSCLC patients.

Clinical Advances
Application and research progress of nanotechnology in atherosclerosis
Tingting WANG,Lili YU,Xiangli SHEN,Junmeng ZHENG,Yushan CHEN,Shasha SHANG,Jianru. WANG
2024, 40(1):  53-58.  doi:10.3969/j.issn.1006-5725.2024.01.010
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Atherosclerosis (AS) is a common cardiovascular disease, and its treatment and prevention have been the focus of medical research. AS an emerging technology, nanotechnology has unique advantages and plays an important role in the prevention, diagnosis and treatment of AS. This paper reviews the latest research on the application of nanotechnology in AS diseases, systematically discusses the role of nanotechnology in the diagnosis and treatment of AS, and comprehensively analyzes the effects of nano-drug carriers based on different surface trimmers, loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment. The aim is to provide new thought for the clinical treatment of AS.

Basic Research
The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study
Tian GU,Chunhong LIU,Fei ZHANG,Wei QIAN,Yanqiu ZHU,Mingliang CHU,Jiemin. LIU
2024, 40(1):  59-64.  doi:10.3969/j.issn.1006-5725.2024.01.011
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Objective To explore the possible mechanism of emodin in inhibiting proliferation, migration, and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1. Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin. CCK8 test, scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells. TCGA database was applied to analyze expressions of HK2, YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues. Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells. Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1. Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells (P < 0.05). CCK8 proliferation test, scratch test, and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS (P < 0.05 for comparisons). Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues (P < 0.05 for comparisons). Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1 (P < 0.05 for comparisons). With supplement of exogenous glycolytic metabolite pyruvate, the protein expressions of oncogenes YAP1 and FOXD1 significantly increased (P < 0.05 for comparisons). Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells, markedly suppressing their biological phenotype. Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism, but also the protein expressions of oncogenes YAP1 and FOXD1. With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway, the protein expressions of oncogenes YAP1 and FOXD1 significantly increased. The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism. Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

Expression of allograft inflammatory factor⁃1 in the testicular model of diabetes mellitus rats
Dechao LI,Mingjin ZHANG,Yibi LAN,Chunlei MA,Weijin. FU
2024, 40(1):  65-71.  doi:10.3969/j.issn.1006-5725.2024.01.012
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Objective To investigate the expression of allograft inflammatory factor-1 (AIF-1) in the testicular model of diabetes mellitus(DM) rats as well as its significance. Methods The rat model of DM testis (DMT) was established, which were randomly divided into the DM testis 4-week group (DMT4W), DM testis s 8-week group (DMT8W) and the DM testis 12-week group (DMT12W). The normal control group (NC group) was randomly divided into three subgroups: NC 4-week (NC4W), NC 8-week (NC8W) and NC 12-week (NC12W). The morphologic changes of testis in the different groups was detected by histopathology. The expression of AIF-1 protein was detected by immunohistochemistry. The expression of AIF-1 and NF-κB p65 protein was observed by immunofluorescence. Results The histopathological results suggested that the numbers of spermatogenic cells, sertoli cells, interstitial cells and sperms in the DMT group were significantly decreased, as compared with the NC group. The immunohistochemistry results showed that the expression of AIF-1 protein was significantly increased in the DMT group, as compared with the NC group (P < 0.05). The intensity of AIF-1 and NF-κB p65 in the DMT group was significantly increased by immunofluorescence, as compared with the NC group. Conclusion The over expression of AIF-1 protein in DMT tissue suggests that it may play an important role in the pathological process of DMT and may become a new therapeutic target and diagnostic marker in the future.

Clinical Research
The association between C⁃reactive protein/albumin ratio and the risk of cardiovascular events in maintenance hemodialysis patients
Yuanmei MU,Jiayuan ZHAO,Ying. ZHANG
2024, 40(1):  72-78.  doi:10.3969/j.issn.1006-5725.2024.01.013
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Objective To explore the association between C-reactive protein/albumin ratio (CAR) and the risk of cardiovascular events in maintenance hemodialysis(MHD)patients. Methods This study enrolled MHD patients who were treated in the blood purification center of the Second Affiliated Hospital of Guangzhou Medical University between August 2016 to December 2019, and the follow-up deadline was March 31, 2021. Collected the clinical data of patients who conform to the inclusion criteria, including demographic, complications, primary basic disease, biochemical indicators of the patients who underwent 3 months regular dialysis treatment and the occurrence of cardiovascular events during the follow-up period. The Kaplan-Meier method was used to estimate the probability of cardiovascular incidents in MHD patients. The Cox proportional hazards model based on generalized propensity score weighting (GPSW) was used to estimate the relationship between CAR and cardiovascular events in MHD patients. Results A total of 170 eligible objects were included in this study, 64 patients with cardiovascular events (37.6%). The Cox proportional hazards model which based on GPSW(HRCAR = 2.087, 95%CI: 1.085 ~ 4.015, P = 0.028), indicated that the hazard ratio of cardiovascular events was 2.087 when the CAR each additional a unit in MHD patients. Conclusion CAR and the risk of cardiovascular events in MHD patients have a significant positive correlation,which can help clinical workers recognize the MHD patients who have high risk of cardiovascular events and intervene in time.

Changes in serum autophagy markers in infants with retinopathy of prematurity and the clinical value
Tao WU,Suming DING,Chang ZHAN,Wenwen CUI,Weihua. TANG
2024, 40(1):  79-84.  doi:10.3969/j.issn.1006-5725.2024.01.014
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Objective To study the changes in serum autophagy markers in children with retinopathy of prematurity (ROP) and its clinical value. Methods Premature infants who were screened for ROP in our hospital from January 2020 to December 2022 were selected as the study subjects. Those screened out with ROP at 4?6 weeks of birth were assigned to the ROP group and those without ROP to the control group. The levels of serum autophagy markers LC3?Ⅱ, Beclin?1 and P62 were detected at the 3rd day, 1st, 2nd and 3rd weeks of birth. The two groups were compared in terms of serum autophagy markers. The diagnostic efficacy of serum autophagy markers on ROP was analyzed. Results There was no significant difference in serum LC3?Ⅱ, Beclin?1 and P62 levels between the ROP group and control group at the 3rd day of birth (P > 0.05). At the first, second and third weeks of birth, however, the ROP group showed significantly lower levels of serum LC3?Ⅱ and Beclin?1 but higher level of P62 compared to the control group (both P < 0.05). The levels of serum LC3?Ⅱ, Beclin?1 and P62 at the first, second and third weeks of birth had diagnostic value for ROP. The children in the ROP group who did not receive mechanical ventilation and oxygen inhalation, and did not develop with sepsis and bronchopulmonary dysplasia showed lower serum LC3?Ⅱ and Beclin?1 levels and higher P62 levels at the first, second and third weeks of birth compared to those without the above?mentioned treatment as well as those complications (all P < 0.05). In the ROP group, those with severe ROP showed lower serum LC3?Ⅱ and Beclin?1 levels and higher P62 levels at the 3rd day, and 1st, 2nd and 3rd week of birth (all P < 0.05). Conclusion The levels of serum autophagy markers in children with ROP show significant changes since the first week of birth, so they have diagnostic efficacy for the diseases.

Effectiveness of high voltage long duration pulsed radiofrequency versus low temperature plasma radiofrequence ablation in the treatment of cervicogenic headache
Xiaojing ZHAO,Hui LIANG,Yuna GUO,Baishan. WU
2024, 40(1):  85-90.  doi:10.3969/j.issn.1006-5725.2024.01.015
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Objective To compare the short?term efficacy and safety of low temperature plasma radiofrequence ablation (LA) vs. high voltage long duration pulsed radiofrequency (HL?PRF) in the treatment of cervicogenic headache (CEH). Methods Eighty patients with cervicogenic headache were divided two groups: one treated with low temperature plasma radiofrequence ablation group as group L (n = 50) and the other treated with high voltage long duration pulsed radiofrequency group as group H (n = 30). The two groups were compared in terms of the score by the Visual Analog Scale, score by the Range of Motion Scale, postoperative pain relief rate, postoperative complication incidence, 1, 4, 12, and 24 weeks after the operation, as well as the therapeutic effectiveness and safety. Results Both groups showed significantly lower VAS and ROM scores after operation (P < 0.05). Compared with group L, group H had significantly lower VAS (all P < 0.05) but insignificantly lower ROM scores (all P > 0.05) at each time point. At T4, group H had significantly higher therapeutic effectiveness rate (P < 0.05) and higher incidence of scalp numbness at T3, as compared to group L (P < 0.05). Conclusion The low temperature plasma radiofrequency ablation and high voltage long duration pulsed radiofrequency both are effective and safe in the treatment of CEH, the latter approach can achieve better therapeutic effectiveness 24 weeks after the operation than the former.

Study on the mutation characteristics of streptomycin genes of Multidrug-Resistant Mycobacterium Tuberculosis in Jiangxi Province
Shengming YU,Lianghua XIA,Jiahuan ZHAN,Siqi LIU,Wei WANG,Liang YAN,Kaisen. CHEN
2024, 40(1):  91-96.  doi:10.3969/j.issn.1006-5725.2024.01.016
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Objective To understand the molecular characteristics of Streptomycin (SM) resistance in multidrug-resistanttuberculosis(MDR-TB) in Jiangxi Province, and to explore the relationship between SM resistant genes (rpsL, rrs and gidB) mutations and SM resistant phenotypes in Beijing genotype TB. Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021, and tested for drug-resistance phenotypes, whether they were Beijing genotype or not and the characteristics of rpsL, rrs and gidB gene mutations. Chi-square test was performed to determine whether rpsL, rrs and gidB mutations were related to genotypes and drug-resistance phenotypes. Results Among 106 cases of MDR-TB, 76 cases were resistant to SM. A total of 58 cases had rpsL 43A > G mutation, 8 cases had 88A > G mutation, 5 cases had rrs mutation, and 3 cases had gidB mutation. Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%, and the specificity and sensitivity were 86.7% and 90.8%, respectively. The isolated rate of Beijing genotype TB was 88.7%, and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs, while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB; in addition, Beijing genotype bacteria were more prone to gene mutations (P = 0.013), but there was no difference in phenotypic drug-resistance. Conclusions Mutations in rpsL, rrs, and gidB genes have a good coincidence rate with phenotypic drug-resistance, and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance; TB genotypes are strongly associated with streptomycin resistance characteristics.

Drugs and Clinic Practice
Effects of different doses of sodium valproate on serum TSH, PRL and DA levels in patients with bipolar disorder
Yanlin LIU,Hui LI,Xiaoliang. ZHOU
2024, 40(1):  97-101.  doi:10.3969/j.issn.1006-5725.2024.01.017
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Objective To explore the effects of different doses of valproate on serum thyroxine (TSH), prolactin(PRL)and dopamine (DA) in patients with bipolar disorder (BPD) level of influence. Methods A total of 90 patients with BPD who received treatment in hospital from May 2020 to May 2022 were selected as the study objects. They were randomly divided into groups A, B and C, with 30 cases in all. Groups A, B and C were orally administered 10 mg/kg, 15 mg/kg and 20 mg/kg sodium valproate every day, respectively. The clinical efficacy, scores of mental diseases before and after treatment, indexes related to blood drug concentration, serum levels before and after treatment, indexes related to liver function and incidence of adverse reactions were compared among the three groups. Results There was no significant difference in the total effective rate among the three groups after treatment (P > 0.05). After treatment, the scores of the three groups were significantly improved compared with before treatment (P < 0.05). There was significant difference in the time to reach the stable state serum concentration (P < 0.05). There were no significant differences in TSH, PRL and DA levels among the three groups after treatment compared with before treatment (P > 0.05). ALT and AST levels in the three groups after treatment were increased compared with those before treatment (P < 0.05), and there were statistically significant differences in ALT and AST levels among the three groups after treatment (P < 0.05). There was significant difference in the incidence of adverse reactions among the three groups (P < 0.05). Conclusion Sodium valproate can effectively treat BPD patients and relieve the degree of mania or depression, but has no significant effect on the level of TSH, PRL and DA. Among them, small dose of sodium valproate can guarantee the therapeutic effect and have less impact on liver function, and less adverse reactions, high safety, worthy of clinical promotion.

A retrospective study on multi⁃targeted small molecule tyrosine kinase inhibitors combined with immune checkpoint inhibitors for 21 patients with advanced solid tumors after standard treatment failure
Dan LIANG,Ying YI,Weifu HUANG,Xiansheng. NONG
2024, 40(1):  102-107.  doi:10.3969/j.issn.1006-5725.2024.01.018
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Objective To investigate the clinical efficacy and safety of the combination therapy of multi?targeted small molecule tyrosine kinase inhibitors (MTKIs) with immune checkpoint inhibitors (ICIs) for late?stage solid tumor in the patients with failed standard treatment regimens. Methods The patients with advanced solid tumors who had been hospitalized in our hospital from January 2021 to January 2023 after failure of ≥ 2 standard treatment regimens were selected and treated with MTKIs combined with ICIs. The efficacy and safety of this regimen were retrospectively studied. Results A total of 21 patients were included. As of March 1, 2022, the overall population had an ORR of 38%, a DCR of 67%, a median progression free survival (mPFS) of 10 months, and a median survival (mOS) of 15 months. Common adverse reactions were pneumonia and oral ulcers. Conclusion For the patients with advanced solid tumors who have failed standard treatment, MTKIs combined with ICIs may be a treatment option, but prospective studies with a larger sample size are needed to confirm the efficacy and safety of this combination therapy and to explore the population most likely to benefit from this treatment method.

Medical Examination and Clinical Diagnosis
Deep learning technology for quality control of echocardiography images
Xinyu LI,Yang WU,Hongmei ZHANG,Lixue YIN,Bo PENG,Shenghua. XIE
2024, 40(1):  108-113.  doi:10.3969/j.issn.1006-5725.2024.01.019
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Objective To Explore the feasibility and value of deep learning technology for quality control of echocardiography images. Methods A total of 180985 echocardiography images collected from Sichuan Provincial People's Hospital between 2015 and 2022 were selected to establish the experimental dataset. Two task models of the echocardiography standard views quality assessment method were trained, including intelligent recognition of seven types of views (six standard views and other views) and quality scoring of six standard views. The predictions of the models on the test set were compared with the results of the sonographer's annotation to assess the accuracy, feasibility, and timeliness of the runs of the two models. Results The overall classification accuracy of the standard views recognition model was 98.90%, the precision was 98.17%, the recall was 98.18% and the F1 value was 98.17%, with the classification results close to the expert recognition level; the average PLCC of the six standard views quality scoring models was 0.933, the average SROCC was 0.929, the average RMSE was 7.95 and the average MAE was 4.83, and the prediction results were in strong agreement with the expert scores. The single-frame inference time after deployment on the 3090 GPU was less than 20 ms, meeting real-time requirements. Conclusion The echocardiography standard views quality assessment method can provide objective and accurate quality assessment results, promoting the development of echocardiography image quality control management towards real-time, objective, and intelligent.

Modernization of Traditional Chinese Medicine
Effects of Busheng Huayu Qianggu prescription in elderly patients with osteoporotic lumbar fracture of kidney deficiency and blood stasis type
Guodong QIU,Lei SUN,Shuihua. XIE
2024, 40(1):  114-118.  doi:10.3969/j.issn.1006-5725.2024.01.020
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Objective To investigate the application value of Bushen Huayu Qianggu prescription in the treatment of senile osteoporotic lumbar fracture with kidney deficiency and blood stasis type. Methods All elderly patients with osteoporotic lumbar fractures of kidney deficiency and blood stasis were treated in our hospital from September 2021 to March 2023 and randomly divided into 68 cases in both groups. The control group was treated with conventional Western medicine, and the observation group was treated with BushengHuayuQiang Gu prescription for 12 weeks. Results Serum D-dimer (D-D), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) were lower in the observation group than in the control group, and vascular endothelial growth factor (VEGF) and β-endorphin (β-EP) were higher (P < 0.05); serum osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) were higher in the observation group (P < 0.05); total effective rate was as high as 95.59% (65%) (P < 0.05); bone mineral density (BMD) was higher in the observation group than in the control group after treatment, and the total symptom score and Cobb angle of Chinese medicine were lower (P < 0.05); the total effective rate of the observation group was as high as 95.59% (65/68), higher than that of the control groupwhich was 80.88%(55/68)(P < 0.05). Conclusion Combined treatment with BushenHuayuQianggu prescription can reduce inflammation, regulate bone metabolism, promote bone mineral density and improve clinical efficacy for senily-aged lumbar osteoporotic fracture caused by kidney deficiency and blood stasis.

Reviews
Application of metagenomics next⁃generation sequencing in the diagnosis and treatment of spinal infection
Siping LONG,Zhili LIU,Shanhu HUANG,Jiaming. LIU
2024, 40(1):  119-122.  doi:10.3969/j.issn.1006-5725.2024.01.021
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The incidence of spinal infections, a relatively rare infectious disease, is on the rise due to the empirical use of antibiotics that increases the chances of infection with drug?resistant bacteria, as well as advances in testing technology that have led to an increase in detection rates. Identifying the type of pathogen to target antibiotics is the key to treatment. However, conventionaldetection methods have low detection rates and are time?consuming, which are not conducive to the rapid and accurate diagnosis of spinal infection. Metagenomics next?generation sequencing (mNGS) is a detection technique that can sequence all nucleic acid fragments in samples,the emergence of which subverts traditional detection methods and plays an important role in the diagnosis and treatment of spinal infections. This article summarizes the application of mNGS in the diagnosis and treatment of spinal infection.

Research progress of the relationship between high fat diet-Induced gastrointestinal microbiota and gastrointestinal cancer
Qi WU,Le BU,Bei. XU
2024, 40(1):  123-128.  doi:10.3969/j.issn.1006-5725.2024.01.022
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In healthy individuals, there is a favourable balance between commensal and potentially pathogenic bacteria. When the balance is broken, the host might suffer from gastrointestinal cancer. Studies have shown that high-fat diet can alter the composition of gastrointestinal microbiota,gastrointestinal microbiota may promote gastrointestinal cancer by affecting metabolites of gastrointestinal microbiota, leading to loss of gastrointestinal barrier function, suppressing anti-tumor immunity, etc. In this work, we will summary the current knowledge on relations and possible mechanisms of high-fat diet-associated gastrointestinal microbiota and gastrointestinal cancer. To provide new ideas for the treatment of gastrointestinal cancer.