Table of Content

21 April 2023, Volume 44 Issue 2

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Advances in modern immunology in infectious diseases, allergic diseases, tumors, and neurological disorders

Chen Yan, Zhang Xulong, Xu Jiangnan, Jia Yufeng, Sun Ying

2023, 44(2):  179-185.  doi:10.3969/j.issn.1006-7795.2023.02.001

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Immunology, as an interdisciplinary subject, involves a variety of subjects and many aspects of different diseases. For the past few years, many breakthroughs have been made in basic and clinical research of immunology, which has deepened the understanding of immunological response and its regulatory mechanism in many common diseases. These findings provide a new scientific basis and clinical means of prevention and treatment for the pathogenesis of immune-related diseases. In this review, we  focus on the key cells and important signaling pathways in immunology, and the role of cytokines in infectious diseases, allergic diseases, tumors and neurological disorders.

Research progress of follicular helper T cells and their roles in antibody-mediated lung transplant rejection

Wang Yi, Ding Yuezhong, Xu Jiangnan

2023, 44(2):  186-195.  doi:10.3969/j.issn.1006-7795.2023.02.002

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Antibody-mediated or humoral rejection in combination with development of de novo donor-specific antibodies (DSA) has been recognized as a significant barrier for long term transplant survival and is responsible for one third of the failed allografts. The lung is one of the most susceptible organs for chronic lung allograft dysfunction (CLAD) which affects about 50% of lung transplant patients. There are two different phenotypes of chronic rejection of lung allografts: (1) restrictive CLAD (rCLAD) or restrictive allograft syndrome (RAS), and (2) bronchiolitis obliterans syndrome (BOS). Patients with rCLAD/RAS have a significantly worse survival compared with BOS patients. Newest studies in mouse model establish an obligatory role for DSA (or alloantibody) production by B cells in the allograft fibrogenesis in RAS after lung transplantation. Therefore, a detailed knowledge of the mechanisms that initiate and maintain B-cell driven anti-donor reactivity is required to prevent and better treat alloresponse in lung transplant patients. During recent years, it became clear that alloantibody response largely depends on the actions of follicular helper T (Tfh) cells. In this overview paper, we review the latest insights on the functions of Tfh cells and their roles in antibody-mediated rejection (AMR), and discuss possible strategies of intervention. 

Ficolin aggravates lipopolysaccharide-induced acute lung injury by regulating polarization of M1 macrophages

Li Yanxiu, Xu Zhixuan, Kong Qingli, Zhou Yujie, Zhang Xulong

2023, 44(2):  196-202.  doi:10.3969/j.issn.1006-7795.2023.02.003

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Objective To investigate the effect and mechanisms of ficolin (Fcn) in acute lung injury induced by lipopolysaccharide (LPS) stimulation. Methods SPF C57BL/6 mice and ficolin gene knockout mice were randomly divided into 6 groups：WT-PBS group， WT-LPS group， Fcna^－/－-PBS group， Fcna^－/－-LPS group， Fcnb^－/－-PBS group and Fcnb^－/－-LPS group, according to the experimental requirements. Acute lung injury model was established after intranasal inoculation with 5 mg/kg LPS for 2 days. H&E staining was used to detect pathological damage of lung tissue. Flow cytometry was used to detect the proportions of neutrophils and macrophages in lung tissue. Western blotting was used to detect the expression of inducible nitric oxide synthase (iNOS) in lung tissue. Bone marrow derived macrophages in wild-type and ficolin knockout mice were isolated and cultured in vitro. After LPS stimulation, the expression of iNOS in cells and the concentration of nitric oxide (NO) in supernatant were detected. Results A mouse model of acute lung injury induced by intranasal inoculation of LPS was successfully established. LPS stimulation aggravated lung pathological injury, with increased pulmonary alveolar fusion and many inflammatory cells infiltration. Besides, the proportions of neutrophils and interstitial macrophages were significantly increased. The expression of iNOS and the production of NO in mouse lung tissue and bone marrow derived macrophages were significantly increased after LPS stimulation in vivo and in vitro. However, knockout of ficolin significantly reduced the recruitment of interstitial macrophages after LPS stimulation. Furthermore, knockout of ficolin ameliorated LPS induced acute lung injury, with reduced iNOS expression and NO production. Conclusion Ficolin can aggravate LPS induced acute lung injury by promoting polarization of M1 macrophages, which may be a potential therapeutic target for acute lung injury.

Immune characteristics of short-term chronic obstructive pulmonary disease model

Zhang Hanxiao, Duan Luo, Zhang Muzhi, Zhang Ruoyang, Zhao Liuyinuo, Zhou Ruonan, Li Yunqi, Lyu Zhe, Wang Jingjing, Yuan Huihui, Cui Ye, Sun Ying, Wang Wei

2023, 44(2):  203-211.  doi:10.3969/j.issn.1006-7795.2023.02.004

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Objective  To analyze the immune characteristics of short-term chronic obstructive pulmonary disease (COPD) model induced by peptide challenge after smoking exposure. Methods  A short-term murine model of COPD was established by smoking sensitization and peptide infusion challenge. Airway inflammation was analyzed by histological staining sections of lung tissues and cells of bronchoalveolar lavage fluid. An invasive lung function test was used to measure changes of lung respiratory mechanical parameters in experimental mice.The Luminex instrument platform was employed to quantify concentrations of cytokines in lung homogenates. Flow cytometry was used to measure changes in the numbers and proportions of subsets of T helper (Th) cells  and innate lymphoid cells (ILCs) in mouse lung tissues. Results  The data showed that short-term tobacco smoke exposure and peptide challenge caused damage of the alveoli, induced airways inflammation with neutrophil infiltration, increased the expression of type 3 cytokines and the numbers of Th17 and ILC3, while decreased proportion of ILC1 and ILC2. Conclusion  The short-term COPD models of smoke sensitization and peptide challenge are dominated by type 3 immunity, in which ILC3 may play a more important role than Th17.

Streptococcus pneumoniae infection at early stage of life affect the severity of asthma induced by exposure to the same bacterial antigens in adulthood

Peng Dan, Pang Jie, Shi Yifan, Cui Lele, Xu Yingjie, Li Yan, Cui Ye, Chen Yan, Yuan Huihui, Qin Xiaofeng, Lyu Zhe, Wang Wei, Sun Ying

2023, 44(2):  212-220.  doi:10.3969/j.issn.1006-7795.2023.02.005

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Objective  To investigate the influence and mechanisms of infection with Streptococcus pneumoniae(SP)at early stage of life and late exposure to the same bacterial antigens on the occurrence and development of asthma.Methods  Mice (one week old of BALB/c background) were infected with SP, then 5 weeks later challenged intranasally with inactivate SP bacteria and interleukin-33 (IL-33)+inactivated SP bacteria to establish model. Lung function and airways hyperresponsiveness (AHR), total cellular and differential counts in bronchoalveolar lavage fluid (BALF) and lungs were measured to evaluate the inflammatory cell infiltration and inflammatory changes in the airways/lungs.The expression levels of IgE and SP specific IgE and IgG in serum, as well as the expression levels of various cytokines in lung homogenates were detected with ELISA.The number of T helper cell (Th) subgroup (Th1, Th2, Th17) and innate lymphoid cells (ILC1, ILC2, ILC3) were measure with flow cytometry. Results  Early-life airways infection with SP and repeated exposure to the same bacterial antigen alone in adulthood failed to induce asthma-like pathological changes. In the presence of IL-33, early-life airways infection with SP and repeated exposure to the same bacterial antigen attenuated asthma-like pathological changes, including the dereased AHR, inflammatory cellular infiltration of the airways,  secretion of mucus and smooth muscle hyperplasia in lung tissue, serum concentrations of IgE and  concentrations of Th2-type cytokines,  numbers of activated Th1, Th2, Th17 and ILC1 cells in the lung tissues, but an increased IL-10 expression, compared with those mice without SP infection in early life. Conclusion  Early-life airways infection with SP attenuted the severity of asthma induced by exposure to the same bacterial antigens in adulthood.

Clinical application of intraoperative visual evoked potentials monitoring

He Min, Ma Jiajia, Han Ruquan

2023, 44(2):  221-225.  doi:10.3969/j.issn.1006-7795.2023.02.006

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With the improvement of people's attention to postoperative visual function, visual evoked potentials (VEP) are applied extensively in perioperative period.It plays an important role in visual pathway tumor related surgery and early diagnosis of optic neuritis and so on. However, there are many influencing factors for VEP monitoring, among which the anesthesia methods and  use of narcotic drugs are common influencing factors. This review analyzed the recent progresses of related VEP research, and discussed improvement of the success rate of VEP monitoring in perioperative period, so as to promote the protection of visual function in perioperative period.

Advances in the effects of stellate ganglion block on cerebral vasospasm due to aneurysmal subarachnoid hemorrhage

hen Yiwei, Wu Youxuan, Liang Fa, Han Ruquan

2023, 44(2):  226-230.  doi:10.3969/j.issn.1006-7795.2023.02.007

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Stellate ganglion block (SGB) is one of sympathetic ganglia block techniques which has been widely used in clinical practice. Recent years, studies of SGB have made  progresses in improving cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). The possible mechanism of cerebral vasospasm after aSAH, the effect of SGB on improving cerebral vasospasm, the clinical application and related mechanism are reviewed in this paper to provide some  theoretical basis for the application of SGB to prevent and treat cerebral vasospasm and delayed cerebral ischemia after aSAH and improve the prognosis.

AClinical characteristics and related factors of consciousness improvement in  patients with prolonged disorders of consciousness during general anesthesia

Wang Xinxin, Yang Wanning, Jian Minyu, Liang Fa, Liu Haiyang, Han Ruquan

2023, 44(2):  231-236.  doi:10.3969/j.issn.1006-7795.2023.02.008

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Objective  To describe the clinical characteristics of patients with prolonged disorders of consciousness (pDOC) under general anesthesia and explore the perioperative clinical factors associated with the improvement of postoperative consciousness in pDOC patients. Methods  We retrospectively collected the medical records and surgical anesthesia data of pDOC patients undergoing elective surgery at Beijing Tiantan Hospital，Capital Medical University from February 2022 to December 2022. The Logistic regression was applied to explore the relationship between postoperative disturbance of consciousness in pDOC patients and perioperative clinical factors. Results  The study included 122 patients who underwent elective general anesthesia, including 72 patients (59.0%) in the vegetative state (VS/UWS) and 50 patients (41.0%) in the minimally conscious state (MCS). A significant improvement in the level of consciousness was observed in 27 patients with pDOC in the hospital after the operation. After using the Logistic regression model to adjust for age, the American Society of Anesthesiologists classification of physical status (ASA) grade, surgical method, sufentanil dosage, remifentanil dosage, awakening time and other related variables, the study found that intraoperative sufentanil dosage (OR=17.23, 95% CI： 1.22－224.30, P=0.035) and recovery time (OR=1.03, 95% CI： 1.00－1.05, P=0.046) were associated with the improvement in postoperative consciousness in the hospital. Conclusion  The short-term postoperative improvement in the hospital consciousness of patients with pDOC may be related to perfect intraoperative analgesia. The recovery time after general anesthesia is expected to be a potential factor predicting the improvement of consciousness in patients with pDOC.

Effects of emergency conversion to general anesthesia on neurological outcomes of patients with acute ischemic stroke undergoing mechanical thrombectomy

Liang Fa, Wu Youxuan, Wang Xinyan, Jian Minyu, Liu Haiyang, Han Ruquan

2023, 44(2):  237-243.  doi:10.3969/j.issn.1006-7795.2023.02.009

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Objective  To investigate the effects of emergency conversion to general anesthesia (EC-GA) on the neurological outcomes of patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT) and predictors of EC-GA. Methods  A retrospective analysis was conducted on 422 patients with AIS who underwent mechanical thrombectomy in Beijing Tiantan Hospital, Capital Medical University from November 2017 to May 2021, including 203 cases in general anesthesia (GA), 173 cases in non-general anesthesia (non-GA)， and 46 cases in EC-GA. The primary outcome was the proportion of patients with Modified Rankin Scale (mRS)≤2 (mRS≤2 means good outcomes of neurological function) at 90 d after the operation. The secondary outcomes included time index ［onset-entry angiographic room time (T1), entry angiographic room-arterial puncture time (T2), arterial puncture-blood flow reperfusion time (T3)］, modified thrombolysis in cerebral infarction (mTICI):(0－2a indicating poor recanalization; 2b－3 indicating good recanalization), mortality (mortality at discharge and 90 d), postoperative complications (incidence of pneumonia and intracranial hemorrhage) and the predictors of EC-GA. Results  Forty-six patients were encountered EA-GA with an overall conversion rate of 21.0%. The conversion rate of AIS patients with anterior circulation occlusion was approximately 19.0%, and that of posterior circulation was approximately 28.9%. There was no statistically significant difference in 90 d mRS and the proportion of good outcome (90 d mRS≤ 2) among the three groups (P>0.05), and the EC-GA group did not have significantly worse outcome with odds ratios: OR=1.538 (95% CI 0.792－2.984), compared with the non-GA group; OR=1.315 (95% CI： 0.684－2.528), compared with the GA group. National Institute of Health Stroke Scale (NIHSS)>15 (entry into angiographic room) was a predictor for EC-GA with an adjusted odds ratio (aOR) =2.005 (95% CI：1.035－3.881). Conclusion  Emergency conversion to general anesthesia did not significantly increase the poor outcome compared with the non-GA group and GA group. Admission NIHSS>15 is a predictor for EC-GA.

Analysis of risk factors of delirium and agitation during anesthesia emergence in pediatric neurosurgery patients

Wang Chengwei, Yuan Linsong, Zhou Yang, Wang Huiwen

2023, 44(2):  244-247.  doi:10.3969/j.issn.1006-7795.2023.02.010

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Objective  To explore the risk factors of delirium and agitation in pediatric neurosurgery patients during anesthesia emergency. Methods  The clinical data of pediatric neurosurgery patients were retrospectively investigated with 120 cases  in the delirium and agitation group, and 392 cases  in the matched control group. Multivariate Logistic regression analysis was used to explore the risk factors of delirium and agitation in pediatric neurosurgery patients during anesthesia emergency. Results  Multivariate Logistic regression analysis showed that oral midazolam before operation (OR=2.695, 95% CI： 1.183－6.139, P=0.018), intraoperative infusion of dexmedetomidine (OR=0.210, 95% CI： 0.049－0.902, P=0.036) and combined inhalation anesthesia (OR=2.862, 95% CI： 1.300－6.301, P=0.009) were the risk factors of delirium and agitation in pediatric neurosurgery patients during anesthesia emergency. Conclusion  Oral midazolam before entering the operating room and combined inhalation anesthesia are independent risk factors for delirium and agitation, and dexmedetomidine can reduce the occurrence of delirium and agitation for pediatric neurosurgery patients.

Expression and mechanism of apoptosis-inducing factor 2 gene in breast cancer

Yang Yifan, Wang Yamei

2023, 44(2):  248-257.  doi:10.3969/j.issn.1006-7795.2023.02.011

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Objective To analyze the expression and mechanism of apoptosis-inducing factor 2 (AIFM2) in breast cancer tissue using bioinformatics methods. Methods The research information of AIFM2 in GEPIA, Kaplan-Meier Plotter, and UALCAN databases were searched, and the expression of this gene in breast cancer was analyzed. The Kaplan-Meier method was used to analyze the relationship between AIFM2 expression and breast cancer patients' survival and clinicopathological factors. Additionally, the LinkedOmic database was used to screen genes co-expressed with AIFM2, and the target genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the tumor immune estimate resource (TIMER) database was used to explore the correlation between AIFM2 expression and infiltration of immune cells into tumor tissues. Results GEPIA database analysis showed that the expression of AIFM2 in breast cancer was significantly lower than that in normal adjacent tissue (P<0.05). Metastasis-free survival was substantially higher in all patients than in the low-expression group (P<0.05); UALCAN database analysis showed that the expression levels of AIFM2 in breast cancer were different in different races, molecular types, and tissue types (P<0.05). There was no difference in expression levels among age, sex, stage, TP53 mutation, menopausal status and lymph node metastasis (P>0.05). GO and KEGG enrichment analysis of AIFM2 co-expressed genes in the LinkedOmic database revealed that the expression level of AIFM2 in breast cancer was positively correlated with the infiltration of CD4^＋T cells, neutrophils, and dendritic cells (P<0.05). Low levels of infiltrating CD4^＋T cells, CD8^＋T cells, neutrophils, and dendritic cells in breast cancer were significantly associated with poorer survival (P<0.05). ConclusionThe expression of AIFM2 in breast cancer is related to the infiltration of immune cells into tumor tissues. Hence, AIFM2 can be considered a biomarker of the immune cell infiltration, metastasis, and prognosis in breast cancer.

Role of retinoic acid and thyroid hormone in chondrogenic differentiation of bone marrow mesenchymal stem cells

Yin Hongyu , Wei Hua, Liu Jinchun

2023, 44(2):  258-264.  doi:10.3969/j.issn.1006-7795.2023.02.012

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Objective   To investigate the effects of thyroxine (T3) and retinoic acid (RA) on chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). Methods   Porcine BMSCs were cultured and induced in three conditioned medium: control group was treated chondrogenic medium  ［with 10^－7 mol/L dexamethasone and 10 ng/mL transforming growth factor-β1 (TGF-β1)］. RA group  was treated chondrogenic medium plus 1 μmol/L  RA. T3 group  was treated chondrogenic medium plus 100 nmol/L T3. BMSCs proliferation was evaluated by MTT assay in a monolayer way. BMSCs pellets in the two groups were harvested after 4 weeks and were evaluated with histological staining and semi-quantitative gene expression analysis. Results   BMSCs proliferation in T3 group was significantly higher than that of control group (P<0.05). BMSCs proliferation in RA group was significantly lower than that of control group (P<0.05). Lacuna-like structure and positive staining of toluidine blue were observed in BMSCs pellets of control group but not in RA group. Better lacuna like structure and positive staining of toluidine blue were observed in BMSCs pellets of T3 group. Expressions of marker genes of chondrogenesis, such as Col Ⅱ, aggrecan and Sox 9, were significantly decreased in RA group compared with control group at week 4, while expression of Col X, a marker gene of hypertrophy, was significantly increased in RA group. The expressions of osteogenesis-related genes Col Ⅰ and Runx 2 also decreased markedly (P<0.05). Expressions of Col Ⅱ, aggrecan and Sox9 were significantly increased in T3 group compared with control group at week 4, and expression of Col X was significantly increased in T3 group (P<0.05). There was no significant difference in the gene expressions of Col Ⅰ and Runx2 between the two groups (P>0.05). Conclusion   RA inhibited proliferation and chondrogensis of BMSCs. T3 promoted the proliferation and chondrogenesis of BMSCs, but induced the hypertrophy of chondrocytes differentiated from BMSCs. 

Certain serum free fatty acids during the first trimester of pregnancy associated with gestational diabetes mellitus

Ma Yuru, Yuan Xianxian, Zheng Wei, Liu Cheng, Wang Jia, Li Guanghui

2023, 44(2):  265-271.  doi:10.3969/j.issn.1006-7795.2023.02.013

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Objective  To explore the relationship between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods  We established a prospective nested case-control study using data from an ongoing cohort, which enrolled women in early pregnancy and followed them up in China. Fourty-three GDM cases were identified and matched on maternal age and pregestational body mass index to 43 pregnant women who did not develop GDM during their pregnancy. Maternal clinical data were collected, including fasting plasma glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high density lipoprotein cholesterol in the first trimester of pregnancy, three point blood glucose of oral glucose tolerance test during the second trimester of pregnancy. Plasma fatty acids were determined by gas chromatography-mass spectrometry. Results  (1) Levels of myristic acid, palmitic acid, palmitoleic acid, stearic acid during the first trimester of pregnancy in GDM group were significantly higher than in control group［（4.35±2.50）μmol/L vs（3.08±1.79）μmol/L,（23.28±8.70）μmol/L vs（18.12±6.94)μmol/L,（7.33±4.69）μmol/L vs（5.22±4.45）μmol/L,（12.50±4.39）μmol/L vs（9.41±3.45）μmol/L, respectively ］. While there were two fatty acids that were significantly lower in GDM group than in control group, which is linolelaidic acid, linolenic acid. Logistic regression indicated that higher levels of palmitic acid（OR=1.32;95% CI:1.14-1.54), palmitoleic acid（OR=1.52;95% CI:1.17-1.99) were associated with higher odds of GDM. However, the level of linolelaidic acid were negatively associated with the incidence of GDM. Conclusion  We documented adverse associations of palmitic acid and palmitoleic acid but a protective association of linolelaidic acid with GDM among Chinese pregnant women.

Levels of sRAGE and IFN-γ in the plasma of patients with acute coronary syndrome and their relationship with the severity of coronary artery lesions

Luo Xiaomeng, Jiang Xue, Du Fenghe, Guo Caixia

2023, 44(2):  272-279.  doi:10.3969/j.issn.1006-7795.2023.02.014

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Objective  To investigate the plasma levels of soluble receptor for advanced glycation end product (sRAGE) and interferon-γ (IFN-γ) in patients with different types of acute coronary syndromes and their relationship with the severity of coronary artery lesions.  Methods  A total of 236 patients who underwent coronary angiography in  Beijing Tiantan Hospital, Capital Medical University from June 2016 to June 2018 were included and divided into acute myocardial infarction group (n=42), unstable angina pectoris group (n=119), non-(coronary heart disease, CHD) group (n=75). The levels of sRAGE and IFN-γ in the plasma of each group were detected and compared by enzyme-linked immunosorbent assay. The differences of sRAGE and IFN-γ in patients with acute myocardial infarction and unstable angina pectoris in different Gensini  score groups and their correlation with the number of coronary artery lesions were analyzed， respectively. The correlations between sRAGE and IFN-γ and myocardial infarction markers cardiac troponin I (cTnI), myoglobin (Myo) and creatine kinase isoenzyme (CK-MB) in patients with acute myocardial infarction were analyzed.  Results The sRAGE level was the highest in the acute myocardial infarction group and the lowest in the non-coronary heart disease group. The level of IFN-γ in the acute myocardial infarction group was higher than that in the unstable angina pectoris group and the non-coronary heart disease group, and there was no significant difference between the unstable angina pectoris group and the non-coronary heart disease group. Multivariate Logistic regression analysis showed that elevated sRAGE level was an independent risk factor for acute myocardial infarction and unstable angina, and was more closely related to acute myocardial infarction. In patients with acute myocardial infarction, sRAGE and IFN-γ were positively correlated, and both were positively correlated with myocardial infarction markers cTnI, Myo, and CK-MB, but had no significant correlation with Gensini score and the number of coronary artery lesions. In unstable angina pectoris, the levels of sRAGE and IFN-γ in the high GS group were higher than those in the medium Gensini group and the low Gensini group. The sRAGE level was the highest in the three-vessel disease group and the lowest in the single-vessel disease group, and the IFN-γ level was the highest in the double-vessel disease group and the lowest in the single-vessel disease group.   Conclusion  The level of sRAGE in the plasma of patients with acute coronary syndrome is significantly increased, and the level of sRAGE in patients with acute myocardial infarction is higher than that in patients with unstable angina pectoris. The levels of sRAGE and IFN-γ in unstable angina pectoris were positively correlated with the severity of coronary artery disease.

Exploration of glucocorticoid combined with anticoagulation in acute/subacute severe cerebral venous thrombosis

Hu Shuyuan, Zhang Kaiyuan, Gu Yaqin, Li Jingka, Zhou Chen, Ji Xunming, Duan Jiangang

2023, 44(2):  280-288.  doi:10.3969/j.issn.1006-7795.2023.02.015

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Objective  To preliminarily investigate the application of glucocorticoid combined with anticoagulant therapy in acute/subacute severe  cerebral venous thrombosis (CVT) through a case series. Methods  Ten patients with acute/subacute severe CVT who were successfully treated with glucocorticoid combined with anticoagulation were enrolled in this study. Neurological deficits, increased intracranial pressure, serum and cerebrospinal fluid inflammatory markers and adverse events were retrospectively analyzed before and after treatment and at 3 months after discharge. Results  Compared with baseline, serum neutrophil-to-lymphocyte ratio（NLR） (P＜0.05),hypersensitive C-reactive protein（hs-CRP）(P＜0.01), interleukin 6（IL-6） (P＜0.01) and cerebrospinal fluid IL-6 (P＜0.01) were significantly decreased in 10 patients at 2 weeks after glucocorticoid pulse therapy; Modified Rankin Scale（mRS） (P＜0.01), National Institutes of Health Stroke Score（NIHSS） (P＜0.01) and intracranial pressure (P＜0.01) were significantly decreased at discharge. At 3 months after discharge, mRS （P＜0.01） and NIHSS （P＜0.01） further decreased. Ten patients had no steroid-related serious adverse reactions such as venous thrombosis recurrence, spontaneous fracture, or osteonecrosis during hospitalization and follow-up. Conclusion  Short-term use of glucocorticoid combined with anticoagulation may be safe and effective in patients with acute/subacute severe CVT.

Effect of intraoperative tranexamic acid application on bleeding in patients undergoing endoscopic resection of skull base chordoma

Jing Longnian, Lei Cheng, Yao Jingxin, Han Ruquan

2023, 44(2):  289-294.  doi:10.3969/j.issn.1006-7795.2023.02.016

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Objective  To investigate the effect of tranexamic acid on intraoperative bleeding in patients with endoscopic resection of skull base chordoma and the safety of its application. Methods  Fifty-eight patients who underwent transendoscopic skull base chordoma resection from July 15, 2021 to October 27, 2022 at Beijing Tiantan Hospital, Capital Medical University were selected. The patients were divided into 30 cases in the tranexamic acid group （ group T） and 28 cases in the 0.9% sodium chloride injection control group  （ group C）  using the random number table method. In group T, tranexamic acid was administered at a loading dose of 20 mg/kg for 15 min at the time of surgical skin incision, followed by continuous pumping at 5 mg·kg^－1·h^－1 till the end of surgery or  till the drug was exhausted, and the total amount of drug did not exceed 2 g. In group control, saline was pumped at the same rate and in the same amount. Intraoperative blood loss, intraoperative and postoperative blood transfusion, duration of surgery, patient coagulation-related indexes at 24 h postoperatively, postoperative complications, unplanned secondary surgery, intensive care unit (ICU） stay, and length of hospital stay were recorded. Results  Intraoperative blood loss in group T was significantly less than that in group C ［4.2  (3.1, 10.0)  mL/kg versus 6.4  (4.3, 13.2)  mL/kg, P<0.05］. The intraoperative transfusion rate was not different with statistically significance between the two groups (P>0.05). However, the postoperative transfusion rate in the group T was significantly less than that in the control group (P<0.05). There were no statistically significant differences in the length of surgery, postoperative 24 h coagulation-related indexes, postoperative complications, unplanned secondary surgery, ICU stay or length of hospitalization between the two groups. Conclusion Intraoperative tranexamic acid in patients undergoing endoscopic resection of skull base chordoma was effective in reducing intraoperative bleeding and postoperative transfusion rates without increasing the incidence of postoperative complications.

Design and verification of screening model of metachronous advanced adenoma for postoperative colorectal cancer patients

Guo Chunmei, Liu Hong, Jiao Yue, Zhang Qian, Wang Canghai, Wang Yadan, Lin Wu, Wei Nan, Zhang Shutian, Wu Jing

2023, 44(2):  295-301.  doi:10.3969/j.issn.1006-7795.2023.02.017

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Objective  To analysis the potential risk factors for metachronous advanced adenoma (MAA) in postoperative colorectal cancer (CRC) patients, so as to develop an individual surveillance scheme and verify it. Methods  Totally 734 CRC patients who underwent surgery from April 2007 to October 2017 were divided into derivation group and validation group, and underwent surveillance colonoscopy for 3 years. Univariate and multivariate logistic analysis were conducted to establish screening model, and verify it in validation group. Results  Totally 734 patients (male/female: 440/294) were finally included. The average age was (64.6 ±11.5) years, and the overall MAA incidence was 11.9% (12.0％ in derivation group and 11.6％ in validation group). Male, diabetes mellitus, right-sided colon cancer, moderately and poorly differentiated adenocarcinoma, synchronous adenoma, synchronous advanced adenoma were independent risk factors for MAA. According to the results of multivariate logistic analysis, MAA screening model and nomogram were established. The area under the curve (AUC) of MAA screening model was 0.957(95% CI: 0.935－0.973), and critical value was 0.938 7. External validation showed that the sensitivity was 93.1%, specificity was 89.1%, and the consistency between screening results and actual results was high (Kappa=0.62). Conclusions  The screening model of metachronous advanced adenoma for postoperative CRC patients was constructed based on seven factors: male, diabetes history, right-sided colon cancer, moderately and poorly differentiated adenocarcinoma, synchronous adenoma, and synchronous advanced adenoma. It had high authenticity and consistency with actual results, and showed clinical application value.

Establishment and validation of an early prediction model for severity of acute pancreatitis

Wang Yadan, Wang Miaomiao, Guo Chunmei, Tai Weiping, Liu Hong, Su Hui, Wang Canghai, Wu Jing

2023, 44(2):  302-310.  doi:10.3969/j.issn.1006-7795.2023.02.018

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Objective To develop a severity prediction model and an online calculator for early prediction of the severity of acute pancreatitis based on simple and readily available clinical indicators for patients with acute pancreatitis within 24 h of admission to the hospital. Methods  The clinical data of 378 patients with acute pancreatitis admitted to Beijing Shijitan Hospital, Capital Medical University, from January 2012 to May 2022 were retrospectively collected and analyzed. According to the Atlanta classification criteria in 2012, 226 patients with mild AP were treated as the mild group (MAP group), and 152 patients with moderate and severe AP were treated as the non-mild group (NMAP group). High risk factors related to the severity of AP were screened through univariate analysis and binary Logistic regression analysis. On this basis, the Logistic regression prediction model is constructed. The receiver operating characteristic  (ROC） curve is used to screen the critical value of the model prediction, calculate the authenticity of the sensitivity and specificity evaluation model prediction, and calculate the consistency between the prediction results of the evaluation model in Kappa and the actual results. Results  A total of 378 patients with AP were included in this study, 252 (66.7%) were males and 126 (33.3%) were females, including 136 cases of moderately severe acute pancreatitis (MSAP) and 16 cases of severe acute pancreatitis (SAP). Univariate analysis revealed that age, diabetes mellitus, hypertension,  heart rate (HR）， white blood cell (WBC）， red blood cell distribution width (RDW）， neutrophils/lymphocyte ratio (NLR）， D-dimer，fibrinogen (FIB），aspartate aminotransferase (AST），  lactate dehydrogenase (LDH）, amylase (AMY）， blood glucose (Glu）， blood urea nitrogen (BUN） and  albumin (ALB） were correlated with the severity of acute pancreatitis (P <0.05), and the above indicators were included in the multivariate analysis, establishing a prediction model equation of Y=－9.487 + 0.363 × RDW (%) + 0.525 × FIB (g/L) + 0.086×Glu (mmol/L)+0.417×LDH (U/L)+0.248×AMY (U/L). The AUC of the prediction model was 0.825, which was greater than the AUC of the correlation index and BISAP score.Calibration curves showed good consistency between predicted risk of NMAP and actual risk of occurrence. The clinical decision curves suggested that when the threshold probability is 0.4-1.0, using this model to predict and identify the development of AP into NMAP and take corresponding treatment measures can make patients benefit in clinical practice. The critical value of NMAP is predicted to be 0.321 according to the maximum point screening model of Yoden index. When the critical value ≥ 0.321 was used to predict NMAP, the sensitivity of model prediction was 69.5%, and the specificity was 86.2%; Kappa value=0.53, indicating that the prediction results of the model have certain authenticity and moderate consistency with the actual results, and have certain clinical application value, but the rate of missed diagnosis is relatively high. Conclusion  The prediction model established based on simple and easily accessible clinical indicators RDW, FIB, Glu, LDH and AMY within 24 h of admission can be used to predict the severity of acute pancreatitis at an early stage, but the rate of missed diagnosis is relatively high, which needs to be further improved.

Serum and multilocus sequence typing  of group B streptococcus colonized in  women at 35－37 weeks of pregnancy and their relationship

Liu Jing, Dong Yuan, Ji Tongzhen

2023, 44(2):  311-315.  doi:10.3969/j.issn.1006-7795.2023.02.019

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Objective  To discuss the serotyping, multilocus sequence typing (MLST) of group B streptococcus (GBS) colonized in reproductive tract of women at 35－37 weeks gestation in an Obstetrics and Gynecology Hospital of Beijing, and to provide reference for clinical prevention and treatment of GBS infection and research and development of vaccines. Methods  Women at 35－37 weeks of gestation were routinely sampled with vaginal and rectal swabs. GBS strains were cultured, identified and isolated. Capsular polysaccharide serotyping and MLST typing were performed by multiplex polymerase chain reaction (PCR) and first generation sequencing， respectively, and the correlation between the two types was analyzed by statistical method. Results  GBS strains were colonized in 147 pregnant women, of which 7 serotypes were found. The first three strains were 38.7% (57/147) of type Ⅲ, 35.3% (52/147) of type Ia, 19.0% (28/147) of type Ib, and 1.4% (2/147) of non-typable (NT) strains. Twenty-two genotypes were found in MLST genotypes. The popular genotypes were ST19 30.6% (45/147), ST10 17.0% (25/147), ST12 12.2% (18/147), ST1 10.2% (15/147) and 3 new genotypes 2.0% (3/147). The correlation between the main serotypes of GBS (Ia, Ib, Ⅲ) and the main types of MLST (ST19, ST10, ST12, ST1) was statistically significant (χ2 =75.29,P< 0.05).The Pearson contingency coefficient was calculated further, C=0.6. Conclusion  In this study, the three most common serotypes (Ⅲ,Ia and Ib) covered 93.2% of GBS colonized in pregnant women (137/147), and GBS capsular polysaccharide protein conjugate vaccines contained the above three serotypes, suggesting that the application of this vaccine may reduce GBS infection in perinatal women in this area. ST19/Ⅲ, ST10/Ia and ST12/Ia types are the main sequence types/serotypes that colonize pregnant women, which provide reference for developing targeted GBS vaccines.In addition, the discovery of new sequences in multilocus sequence typing supplements the MLST database of group B streptococcus.

Comparison of three methods for augmenting peri-implant buccal keratinized mucosa

Lin Shichen, Liu Hang, Wu Xue, Li Xin, Ji Yiming, Duan Shaoyu

2023, 44(2):  316-321.  doi:10.3969/j.issn.1006-7795.2023.02.020

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Objective  To explore and evaluate the clinical effects of three methods in augmenting keratinized tissue around dental implant, provide evidence for clinical application. Methods  Totally 36 patients in need for augmenting the buccal keratinized mucosa around implants in  Electric Power Teaching Hospital，Capital Medical University from June 2019 to June 2021, were randomly divided into three groups with 12 cases in each group. They were treated with allogeneic acellular dermal matrix (ADM), concentrated growth factors (CGFs), free gingival graft (FGG) to increase the buccal keratinized mucosa width. The pain degree was recorded by Visual Analogue Scale (VAS) one week after surgery. The keratinized tissue width (KTW) of the three groups were measured 6 months after surgery and the aesthetic satisfaction was recorded by VAS. Results  Six months after surgery, the KTW was (3.72 ± 1.18) mm in ADM group, (2.92 ± 0.72) mm in CGFs group and (4.65 ± 0.91) mm in FGG group, which were significantly increased compared with the preoperative. There were significant differences in keratinized mucosa gain(ΔKTW) among ADM group ［(2.75 ± 0.96) mm］, CGFs group ［(1.84 ± 0.65) mm］ and FGG group ［(3.49 ± 0.79) mm］ (P<0.05); The VAS score of postoperative pain in FGG group (3.50 ± 1.17) was significantly higher than that in ADM group (2.25 ± 1.06) and CGFs group (2.00 ± 0.95), with significant difference between three groups (P<0.05). The VAS score of aesthetic satisfaction 6－months postoperatively in ADM group (8.67 ± 0.89) and CGFs group (8.17 ± 0.94) were significantly higher than that in FGG group (6.00 ± 1.28), with significant difference between three groups (P<0.05). Conclusion  ADM, CGFs and FGG can effectively increase the KTW around implants, however have different characteristics. Clinically, they can be selected reasonably according to the situation of patients and the conditions of medical institutions.

Clinical analysis of gastric xanthomas with intestinal metaplasia

hi Tianyu, Zhao Quchuan

2023, 44(2):  322-327.  doi:10.3969/j.issn.1006-7795.2023.02.021

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Objective  To retrospectively analyze the clinical characteristics of patients with gastric xanthoma (GX) combined with intestinal metaplasia. Methods  Totally 68 391 patients who underwent initial gastroscopy in the digestive endoscopy center of Xuanwu Hospital, Capital Medical University between January 2012 and January 2022 were selected and 1 346 cases were diagnosed with GX, with a GX detection rate of 1.97% and a mean age of (55.4 ± 12.1) years old. GX cases were divided into two groups according to the presence or absence of intestinal metaplasia: GX with intestinal metaplasia (n=901) and GX without intestinal metaplasia (n=445). The two groups were compared with respect to age, gender，Helicobacter pylori (HP)，degree of gastric mucosal atrophy and the presence or absence of concomitant gastric cancer. The GX with intestinal metaplasia group was further divided into three subgroups according to the degree of intestinal metaplasia: GX with mild intestinal metaplasia (n=412), GX with moderate intestinal metaplasia (n=291) and GX with severe intestinal metaplasia (n=198), and the clinical characteristics of different subgroups of GX with intestinal metaplasia were analyzed comparatively. Results  There were significant differences between GX with and without intestinal metaplasia in terms of age (P=0.012), HP infection(P<0.001） and gastric cancer (P=0.014); GX with intestinal metaplasia was associated with a higher incidence of elderly patients, a higher HP infection and a higher detection rate of concomitant gastric cancer. Univariate and multivariate analysis showed that there were significant differences in age (P<0.001), HP infection (P<0.001), gastric mucosa atrophy (P<0.001) and intestinal metaplasia (P=0.014) between GX group and non-gastric cancer group. All three subgroups showed significant differences in age (P <0.001), gender (P=0.004), degree of gastric mucosal atrophy (P<0.001) and gastric cancer (P<0.001). The GX group with moderate or severe intestinal metaplasia had a higher proportion of elderly subjects (P=0.002, P=0.008). Gastric mucosal atrophy of various degrees was the mildest in the GX with mild enteropathy group (P<0.001), and the GX with severe intestinal metaplasia group had the highest degree of combined severe gastric mucosal atrophy (P<0.001) and a higher proportion of combined gastric cancer (P<0.001). Conclusion  The occurrence of GX with intestinal changes is associated with gastric cancer and atrophic gastritis, which needs to be further demonstrated by multicenter and large sample studies.

Discussion on new technologies for adaptive elimination of set-up accumulation errors in whole-brain radiotherapy for childhood germ cell tumor

Wang Tianfu, Li Xingyue, Ma Mingxu, Guan Dawei, Xu Haiyan, Gong Jin

2023, 44(2):  328-334.  doi:10.3969/j.issn.1006-7795.2023.02.022

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Objective  To investigate the feasibility of adaptive radio therapy (ART) based on image guided-radiotherapy (IGRT) for pediatric germ cell tumors and to provide a basis for clinical whole-brain ART. Methods  A retrospective study was performed for 20 patients with germ cell tumors (GCTs) of the central nervous system who underwent whole brain prophylactic radiotherapy. Each patient underwent cone beam computed tomography (CBCT) once a week for the first three and subsequent treatments for a total of 7 sessions. Record the positioning error values in the lateral (LAT),  longitudinal (LNG), and vertical (VRT) directions during the entire treatment process. The original plan was named Plan_A, and a new treatment center point (ISO) regression treatment plan system was generated due to the positioning error value, and the volume dose was calculated without changing the field weight and field distribution, and the Plan Sum function was used to add the cumulative positioning error to generate a new plan to obtain Plan_B. The new plan generated by the cumulative positioning error is quickly optimized by the Acuros XB algorithm and added to the Plan Sum function to obtain Plan_C. The target and organ at risk (OAR) dose changes of Plan_A, Plan_B and Plan_C were compared, and the statistical differences were verified by Wilcoxon's paired rank test. Results  Compared with Plan_A, Plan_B homogeneity index (HI) 95  planning target volume(PTV) and HI98 PTV were 1.058 4－1.084 7. Conformity index (CI) PTV was 0.934 4. CTV D_min relative deviation was -7.22%, P=0.000 7. OAR relative deviation was －0.1%－9.8%. Compared with Plan_ A, HI95 PTV and HI98 PTV of Plan_ C were 1.056 9－1.078 8. CI PTV was 0.936 5. CTV D_min relative deviation was -1.69%, P=0.545 9. OAR relative deviation was  －0.15%－3.40%. Conclusion  There were statistical differences in the cumulative positioning error of whole brain radiotherapy for childhood germ cell tumor on the dose of target area and endangered organs, and the cumulative positioning error led to the deterioration of target uniformity and conformity, the Dmin change of CTV exceeded 5%, and the OAR reception increased. ART rescheduling can bring target uniformity and conformity and the amount of hazardous organs closer to the original plan. At the same time Plan_B although there is a relative deviation, the absolute dose of the endangering organ is within a reasonable range.

Clinical features of primary central nervous system malignant melanoma

Wang Haoran, Gu Chunyu, Qu Yanming, Liu Ning, Ning Weihai, Ji Junpeng, Zhang Mingshan

2023, 44(2):  335-342.  doi:10.3969/j.issn.1006-7795.2023.02.023

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Objective  To summarize the clinical, imaging, therapeutic and prognostic features of primary central nervous system (CNS) malignant melanoma(MM). Methods  The clinical data of 17 patients with primary CNS MM admitted to the  Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, during 2011-2021 were divided into four clinical types for retrospective analysis. Results  The male to female ratio was 11∶6, and the mean age was (39.9±16.6) years. Among them, 6 cases were type A, 5 type B, 4 type C, and 2 type D. There were 11 cases of cranial hypertension, 9 cases of local nerve dysfunction and 3 cases of epilepsy. High T1 signal was observed in 12 cases on magnetic resonance imaging（MRI） scan. There were 13 cases had seeding metastasis, 11 of which were linear. The fourteen cases underwent surgical resection, 3 cases underwent biopsy, and 6 cases underwent anti-tumor therapy after surgery. Overall, the median overall survival (mOS) was 7 months, and the survival of patients with combined treatment was significantly longer than that with surgery alone ［(20.6±7.9) months  vs  (3.3±0.9) months, P=0.001］. There were significant differences in symptoms, imaging, and treatment among the 4  clinical types. Conclusion  The incidence of primary CNS malignant melanoma is low, and most of them have obvious imaging features, which can be divided into four clinical types. The disease requires surgery combined with radiotherapy and other comprehensive treatment, yet now the prognosis is stile poor.

Clinical analysis of immune-related adverse events in gastrointestinal cancer

Sun Jing, Shi Youwu, Du Feng, Yang Ying, Sun Zhiwei, Yu Jing, Xiao Yanjie, Zhang Xiaodong, Jia Jun

2023, 44(2):  343-350.  doi:10.3969/j.issn.1006-7795.2023.02.024

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Objective To identify the characteristics and risk factors associated with immune-related adverse events (irAEs) in gastrointestinal cancer patients treated with immune checkpoint inhibitors (ICIs). Methods  We retrospectively investigated clinical data of 95 gastrointestinal cancer patients from April 2019 to October 2021 in Peking University Cancer Hospital. The clinical characteristics and irAEs data of these patients were analyzed. Binary Logistic regression analysis was used to identify irAEs and endocrine irAEs risk factors. Results  In the 95 patients enrolled, the total number and median number of ICIs treatment cycles were 458 and 3(range:1-33). The incidence of irAEs and grade 3-4 irAEs were 55.8% and 9.5%, respectively. The most common irAEs were skin irAEs (27.4%) and endocrine irAEs (22.1%). Among endocrine irAEs, hypothyroidism occurred most frequently (16.8%), while adrenocortical dysfunction (2.1%) and hypophysitis (1.1%) were rare. Most irAEs occurred in the early stage of immunotherapy, and 78.2% occurred within 12 weeks. The earlier onset irAEs were allergy and skin irAEs, with a median occurrence time of 2 weeks (range:0.9－3.1 weeks) and 3.8 weeks (range:0.9－17.9 weeks), respectively. The median onset time of endocrine irAEs was 6.9 weeks (range:3.0－52.1 weeks). Multivariate analysis revealed that female(OR=5.197,95%CI：1.166－23.154,P=0.031） and microsatellite instability-high (MSI-H）(OR=35.048, 95%CI：2.756－445.787, P=0.006）were independent risk factors of endocrine irAEs. Immunotherapy combined with chemotherapy (OR=0.107, 95%CI：0.021－0.412, P=0.001） was an independent protective factors. Conclusion  The application of ICIs in patients with gastrointestinal cancer was well tolerated. Female and MSI-H patients have an increased risk of endocrine irAEs. Immunotherapy combined with chemotherapy may reduce the risk of endocrine irAEs.

Progresses on the effect of estrogen on innate immune cells

Li Ziyi, Wang Xi, Liang Pu

2023, 44(2):  351-357.  doi:10.3969/j.issn.1006-7795.2023.02.025

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The immune system has gender dimorphism. Females mount stronger innate immunity and adaptive immune response  than males, and female sensitivity to multiple pathogenic infections and malignant tumors is lower. Meanwhile, women are more likely to develop autoimmune diseases. One of the important factors responsible for these sex differences, estrogen, exerts a wide range of biological effects in the human body. Currently, estrogen has been reported to regulate the differentiation, maturation, longevity, and effector function of innate immune cells, including neutrophils, monocytes and macrophages, natural killer cells, and dendritic cells. This review discusses in detail how estrogen regulates the normal physiological function of immune cells and its different roles in various disease states.