1.Pathological Consequences of Altered Palmitoylation in Neurodegenerative Disorders and Its Potential as a Therapeutic Target
Wen-Ying LIU ; Shu-Heng WANG ; Jian-Ping JIA
Progress in Biochemistry and Biophysics 2024;51(10):2340-2356
Protein palmitoylation, a prevalent and dynamic form of S-acylation modification, plays a critical role in maintaining the functionality of the nervous system. This reversible process involves the attachment of palmitic acid to cysteine residues in proteins, anchoring them to cellular membranes and regulating their spatial distribution. The functioning of palmitoylation is crucial for normal neuronal activities, influencing key processes such as signal transduction, synaptic function, and protein trafficking. Recent research has increasingly underscored the significance of specific zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S-acyltransferases in neuronal development and synaptic plasticity. These enzymes, which catalyze the palmitoylation of proteins, have emerged as pivotal regulators of brain function. Dysregulation of palmitoylation by these enzymes is now recognized as a potential contributor to the pathogenesis of various neurodegenerative diseases. This review provides an in-depth analysis of the expression patterns and functional diversity of ZDHHC enzymes across different brain regions and cell types. ZDHHC enzymes exhibit significant sequence variability and demonstrate region-specific and cell type-dependent expression. Such heterogeneity suggests that these enzymes may have specialized roles in different areas of the nervous system, making them crucial modulators of neuronal function and synaptic transmission. The review also explores the regulatory mechanisms of protein palmitoylation and their implications in neurodegenerative disease onset and progression. Altered palmitoylation can lead to the destabilization and subsequent aggregation of these proteins, exacerbating neurodegenerative processes. Abnormal palmitoylation of α‑synuclein can either promote or inhibit its aggregation in Parkinson’s disease pathology. Proteins related to these key pathological factors, including amyloid precursor protein (APP) and beta-secretase 1 (BACE1), are also influenced by palmitoylation, contributing to the formation of amyloid plaques through the aggregation of Aβ. Additionally, ZDHHC13 and ZDHHC17, which are abundantly and widely expressed in the brain, play crucial roles in this process. For instance, reduced interaction between ZDHHC17 and huntingtin could significantly contribute to the pathogenesis of Huntington’s disease. Thus, modulating the palmitoylation status of these proteins presents a promising therapeutic strategy to prevent their toxic aggregation and mitigate neuronal damage. Actually, regulating palmitoylation has shown potential for therapeutic interventions in neurodegenerative diseases, with studies demonstrating that modulation of palmitoylation can restore neuronal function and improve disease symptoms. Regulating palmitoylation holds significant promise for therapeutic strategies in neurodegenerative diseases, as modulation of this process can restore neuronal function and ameliorate disease symptoms. However, progress is hindered by the lack of high-resolution structural data and comprehensive targeting maps for specific ZDHHC enzymes. Additionally, current detection methods for palmitoylation, which focus on labeling and analyzing palmitic acid and cysteine residues, are often complex and time-consuming, and may produce inconsistent palmitoyl-proteomic profiles. These methodological challenges underscore the need for more robust and efficient detection technologies. A deeper understanding of palmitoylation’s role in neurological diseases, coupled with the development of improved detection methods, is essential for advancing our knowledge of the molecular underpinnings of these conditions and for the creation of innovative therapeutic strategies aimed at combating neurodegenerative diseases.
2.Chest computed tomography manifestations in neonates with chronic granulomatous disease
Heng SHU ; Li-Li WANG ; Tong-Sheng YE ; Xian-Hong LIN ; Shao-Hua BI ; Yu-Hong ZHAO ; Ping-Sheng WANG ; Li-Yin DAI
Chinese Journal of Contemporary Pediatrics 2024;26(7):730-735
Objective To study chest computed tomography(CT)manifestations in neonates with chronic granulomatous disease(CGD)to provide clues for early diagnosis of this disease.Methods A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital.Results Nine neonates with CGD were included,with eight presenting respiratory symptoms as the initial sign.Chest CT findings included:consolidation in all 9 cases;nodules in all 9 cases,characterized by multiple,variably sized scattered nodules in both lungs;masses in 4 cases;cavities in 3 cases;abscesses in 6 cases;bronchial stenosis in 2 cases;pleural effusion,interstitial changes,and mediastinal lymphadenopathy each in 1 case.CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement;no signs of pulmonary emphysema,lung calcification,halo signs,crescent signs,bronchiectasis,or scar lesions were observed.There was no evidence of rib or vertebral bone destruction.Fungal infections were present in 8 of the 9 cases,including 6 with Aspergillus infections;three of these involved mixed infections with Aspergillus,with masses most commonly associated with mixed Aspergillus infections(3/4).Conclusions The primary manifestations of neonatal CGD on chest CT are consolidation,nodules,and/or masses,with Aspergillus as a common pathogen.These features can serve as early diagnostic clues for neonatal CGD.
3.Metabolic Disease Management Guideline for National Metabolic Management Center(2nd edition)
Weiqing WANG ; Yufan WANG ; Guixia WANG ; Guang NING ; Dalong ZHU ; Ping LIU ; Libin LIU ; Jianmin LIU ; Zhaoli YAN ; Xulei TANG ; Bangqun JI ; Sunjie YAN ; Heng SU ; Jianling DU ; Sheli LI ; Li LI ; Shengli WU ; Jinsong KUANG ; Yubo SHA ; Ping ZHANG ; Yifei ZHANG ; Lei CHEN ; Zunhai ZHOU ; Chao ZHENG ; Qidong ZHENG ; Zhongyan SHAN ; Dong ZHAO ; Zhigang ZHAO ; Ling HU ; Tingyu KE ; Yu SHI ; Yingfen QIN ; Mingjun GU ; Xuejiang GU ; Fengmei XU ; Zuhua GAO ; Qijuan DONG ; Yi SHU ; Yuancheng DAI
Chinese Journal of Endocrinology and Metabolism 2023;39(6):538-554
The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.
4.Preliminary survey report on the clinical validation of in-use electronic sphygmomanometers in China.
Xiang Hui ZHANG ; Yu Qing ZHANG ; Rong HU ; Ping SONG ; Xu HAN ; Shu Lin WEN ; Heng GUO ; Lin CHEN ; Shao Bo XIAO ; Yang Feng WU
Chinese Journal of Cardiology 2023;51(4):407-414
Objective: To explore the percentage of in-use electronic sphygmomanometers independently validated clinically in China. Methods: We conducted a cross-sectional survey and Beijing, Shenzhen, Shijiazhuang, Datong, and Shihezi were selected according to the geographical location and economic level. In each site, one tertiary hospital, two community health centers, and 20 families with electronic sphygmomanometers in use were chosen. The information of electronic sphygmomanometers including brand, model, manufacturer and production date were obtained by the trained staff. Ten electronic sphygmomanometers from each hospital, five electronic sphygmomanometers from each community health center, and one electronic sphygmomanometer from each family were surveyed, and the user's subjective judgment results and judgment basis on the accuracy of the electronic sphygmomanometer measurement were collected. We searched six registration websites (Medaval, Stride BP, dabl Educational Trust, British and Irish Hypertension Society, American Medical Association and Hypertension Canada) and two research databases (PubMed and CNKI) for the clinical validation status of each electronic sphygmomanometer. Results: A total of 200 electronic sphygmomanometers were investigated in this study, of which only 29.0% (58/200) passed independent clinical validation. When stratified by users, the percentage of being clinical validated was 46.0% (23/50) for electronic sphygmomanometers in hospitals, 42.0% (21/50) for those in community health centers and 14.0% (14/100) for those in home use, respectively, and the proportions between the three groups were significantly difference (P<0.001). Doctors in tertiary hospitals and community health service centers judged the accuracy of electronic sphygmomanometers mainly on the basis of "regular correction" (41.0% (41/100)) and "comparison with other electronic sphygmomanometers" (20.0% (20/100)), while among home users, 41.0% (41/100) were not clear about the accuracy of electronic sphygmomanometers, and 40.0% (40/100) made the judgment by "comparison with the devices in hospitals". Conclusion: The clinical validation of in-use electronic sphygmomanometers in China is low. Most of users, including healthcare professionals, are not aware of clinical validation of electronic sphygmomanometers.
Humans
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Blood Pressure Determination
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Cross-Sectional Studies
;
Sphygmomanometers
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Hypertension/diagnosis*
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China
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Electronics
;
Blood Pressure
5.Clinical characteristics and genetic analysis of a neonate with Smith-Magenis syndrome.
Heng SHU ; Tongsheng YE ; Guanghui LIU ; Liying DAI ; Ping ZHA ; Xianhong LI ; Yuwei ZHAO ; Xiaoshan ZHU ; Hong ZHENG
Chinese Journal of Medical Genetics 2022;39(4):409-412
OBJECTIVE:
To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS).
METHODS:
Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed.
RESULTS:
On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent.
CONCLUSION
SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.
Adult
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Chromosome Deletion
;
Chromosomes, Human, Pair 17
;
DNA Copy Number Variations
;
Genetic Testing
;
Humans
;
Infant, Newborn
;
Intellectual Disability/genetics*
;
Male
;
Phenotype
;
Smith-Magenis Syndrome/genetics*
6.Regulatory effects of bio-intensity electric field on transformation of human skin fibroblasts.
Wen Ping WANG ; Ran JI ; Ze ZHANG ; Ya Ting WU ; Heng Shu ZHANG ; Qiong ZHANG ; Xu Pin JIANG ; Miao TENG
Chinese Journal of Burns 2022;38(4):354-362
Objective: To investigate the regulatory effects of bio-intensity electric field on the transformation of human skin fibroblasts (HSFs). Methods: The experimental research methods were used. HSFs were collected and divided into 200 mV/mm electric field group treated with 200 mV/mm electric field for 6 h and simulated electric field group placed in the electric field device without electricity for 6 h. Changes in morphology and arrangement of cells were observed in the living cell workstation; the number of cells at 0 and 6 h of treatment was recorded, and the rate of change in cell number was calculated; the direction of cell movement, movement velocity, and trajectory velocity within 3 h were observed and calculated (the number of samples was 34 in the simulated electric field group and 30 in 200 mV/mm electric field group in the aforementioned experiments); the protein expression of α-smooth muscle actin (α-SMA) in cells after 3 h of treatment was detected by immunofluorescence method (the number of sample was 3). HSFs were collected and divided into simulated electric field group placed in the electric field device without electricity for 3 h, and 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group which were treated with electric fields of corresponding intensities for 3 h. Besides, HSFs were divided into simulated electric field group placed in the electric field device without electricity for 6 h, and electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group treated with 200 mV/mm electric field for corresponding time. The protein expressions of α-SMA and proliferating cell nuclear antigen (PCNA) were detected by Western blotting (the number of sample was 3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test, and least significant difference test. Results: After 6 h of treatment, compared with that in simulated electric field group, the cells in 200 mV/mm electric field group were elongated in shape and locally adhered; the cells in simulated electric field group were randomly arranged, while the cells in 200 mV/mm electric field group were arranged in a regular longitudinal direction; the change rates in the number of cells in the two groups were similar (P>0.05). Within 3 h of treatment, the cells in 200 mV/mm electric field group had an obvious tendency to move toward the positive electrode, and the cells in simulated electric field group moved around the origin; compared with those in simulated electric field group, the movement velocity and trajectory velocity of the cells in 200 mV/mm electric field group were increased significantly (with Z values of -5.33 and -5.41, respectively, P<0.01), and the directionality was significantly enhanced (Z=-4.39, P<0.01). After 3 h of treatment, the protein expression of α-SMA of cells in 200 mV/mm electric field group was significantly higher than that in simulated electric field group (t=-9.81, P<0.01). After 3 h of treatment, the protein expressions of α-SMA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were 1.195±0.057, 1.606±0.041, and 1.616±0.039, respectively, which were significantly more than 0.649±0.028 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of α-SMA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly increased (P<0.01). The protein expressions of α-SMA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were 0.730±0.032, 1.561±0.031, and 1.553±0.045, respectively, significantly more than 0.464±0.020 in simulated electric field group (P<0.01). Compared with that in electric field treatment 1 h group, the protein expressions of α-SMA in electric field treatment 3 h group and electric field treatment 6 h group were significantly increased (P<0.01). After 3 h of treatment, compared with that in simulated electric field group, the protein expressions of PCNA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 100 mV/mm electric field group, the protein expressions of PCNA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 200 mV/mm electric field group, the protein expression of PCNA of cells in 400 mV/mm electric field group was significantly decreased (P<0.01). Compared with that in simulated electric field group, the protein expressions of PCNA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were significantly decreased (P<0.01); compared with that in electric field treatment 1 h group, the protein expressions of PCNA of cells in electric field treatment 3 h group and electric field treatment 6 h group were significantly decreased (P<0.05 or P<0.01); compared with that in electric field treatment 3 h group, the protein expression of PCNA of cells in electric field treatment 6 h group was significantly decreased (P<0.01). Conclusions: The bio-intensity electric field can induce the migration of HSFs and promote the transformation of fibroblasts to myofibroblasts, and the transformation displays certain dependence on the time and intensity of electric field.
Actins/biosynthesis*
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Cell Differentiation/physiology*
;
Cell Movement/physiology*
;
Electric Stimulation Therapy
;
Electricity
;
Fibroblasts/physiology*
;
Humans
;
Myofibroblasts/physiology*
;
Proliferating Cell Nuclear Antigen/biosynthesis*
;
Skin/cytology*
7. Electroacupuncture Inhibits Neuronal Apoptosis Induced by Bilirubin Encephalopathy in SD Suckling Rats by Regulating NGB and PI3K/Akt Signaling Pathways
Jia-Heng HU ; Li-Rong ZHANG ; Yi-Ying WANG ; Ling LONG ; Zhi-Han HU ; Wei-Min YUAN ; Jing-Wen ZHAO ; Shu-Juan ZHU ; Juan HUANG ; Guo-Ping QIU ; Sheng-Wei GAN ; Ping FAN
Chinese Journal of Biochemistry and Molecular Biology 2021;37(6):772-781
Objective In this study, electroacupuncture (EA) was used to analyze the expression changes of related proteins in neuroglobin (NGB), PI3K/AKT and apoptotic pathways in the temporal cortex of bilirubin encephalopathy (BE) rats, so as to investigate the therapeutic effect of EA on BE and the relevant mechanism of NGB in this process. Totally 39 seven-day-old SD rats were divided into Sham, BE model and BE+EA groups. The neonatal BE model was established by injecting bilirubin solution (10 μg UCB/g Weight) into the cerebellomedullary cistern, Sham group was injected with the same amount of normal saline. BE rats were treated with EA at Baihui (GV20) and Quchi (LI11) acupoints with the frequency of 2/15 Hz for 15 min. Treatment was performed 12 h before modeling, followed by treatment every 12 h, in a total of three times. HE, Nissl staining and electron microscopy (TEM) were used to observe the pathological and ultrastructural changes of nerve cells in each group. Results showed that EA treatment reduced the damage of cortical neurons of BE rats and increase the number of Nissl bodies. TEM confirmed that EA treatment could alleviate the degree of mitochondria edema. Immunofluorescence staining was used to detect the expression sites and cell types of NGB. Results showed that NGB was mainly expressed in cortical neurons. Western blotting showed that EA treatment increased the expression of NGB, PI3K (p110 alpha), pAKT (Ser473) (P< 0. 05, P< 0. 05 and P< 0. 01, respectively) and the ratio of apoptosis-related protein Bcl-2/Bax (P < 0. 001), decreased the expression of Cleaved Caspase-3 (P< 0. 05) in the temporal cortex of rats. TUNEL staining showed that EA reduced the number of apoptotic cells (BE group 186. 00±13. 86 vs BE+EA group 78. 67±11. 85, P< 0. 01) . This study confirms that EA can promote the expression of NGB in the temporal cortex of BE rats, then activate the PI3K/AKT pathway to exert its neuroprotective function and inhibit the occurrence of apoptosis. EA may become a potential treatment method for BE.
8.Soil ecological effect of attapulgite and its application prospect in ecological planting of Chinese materia medica.
Jun LUO ; Yin-Quan WANG ; Lan-Ping GUO ; Zhen-Heng WANG ; Shu-Nan LI ; Tong PENG ; Qin LI ; Yang-Yang YAO ; Zheng-Mei QI ; Jiang-Tao NIE
China Journal of Chinese Materia Medica 2020;45(9):2031-2035
The long-term and extensive use of chemical fertilizers and pesticides in the cultivation of Chinese materia medica has resulted in serious soil ecological and environmental problems such as secondary salinization, soil consolidation, soil acidification, continuous cropping obstacles, micro-ecological imbalance, and serious soil pests and diseases in the production areas of Chinese materia medica. Therefore, promoting the ecological planting of Chinese materia medica is the only way for the production of Chinese materia medica. Attapulgite(ATP) is a kind of water-rich magnesium-rich aluminosilicate clay mineral with layered and chain structure. It has abundant reserves in China, possesses nano-material properties, strong adsorption and ion exchange properties, and has huge high value utilization space. ATP and its functional products have the potential of water and fertilizer conservation, regulating soil structure and micro-ecology, and are widely used in ecological planting of Chinese materia medica. This paper reviews the resource distribution, structural characteristics, the research and application progress in soil ecological effects of ATP, and prospects the application prospects of it in the ecological planting of Chinese materia medica.
China
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Drugs, Chinese Herbal
;
Magnesium Compounds
;
Materia Medica
;
Medicine, Chinese Traditional
;
Silicon Compounds
;
Soil
9.Prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis: a report of 995 cases
Rongjian ZHOU ; Heng ZHANG ; Ping SHU ; Hongshan WANG ; Zhenbin SHEN ; Fenglin LIU ; Jing QIN
Chinese Journal of Digestive Surgery 2019;18(3):250-258
Objective To investigate the prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis.Methods The retrospective case-control study was conducted.The clinicopathological data of 995 patients with stage Ⅲ gastric cancer who were admitted to the Zhongshan Hospital of Fudan University between January 2003 and December 2014 were collected.There were 690 males and 305 females,aged from 20 to 75 years,with an average age of 61 years.After clinical staging according to results of preoperative accessory examinations,patients with early gastric cancer underwent D1+ lymphadenectomy,patients with advanced gastric cancer underwent D2 lymphadenectomy and patients with serosa invasion underwent D2+ lymphadenectomy.Observation indicators:(1) treatment situations;(2) follow-up and survival situations;(3) prognostic factors analysis after operation;(4) stratified analysis:① stratified analysis of tumor pathological N staging;② stratified analysis of number of lymph node dissected;③ stratified analysis of tumor pathological TNM staging;(5) receiver operating characteristic (ROC) curve.Patients were followed up using outpatient examination and telephone interview to detect postoperative survival up to January 2016.The overall survival time was from the operation data to last follow-up or time of death.Measurement data with normal distribution were represented as Mean±SD.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and Log-rank test was used for survival analysis.The COX proportional hazard model was used for univariate and multivariate analysis.The ROC curve and area under curve (AUC) were used to check the accuracy of number of positive lymph nodes and metastatic lymph node ratio for prognosis.Comparison of the AUC was analyzed by the Z test.Results (1) Treatment situations:of 995 patients underging gastrectomy,677 underwent distal gastrectomy,85 underwent proximal gastrectomy,233 underwent total gastrectomy.There were 117 undergoing D1+ lymphadenectomy and 878 undergoing D2 lymphadenectomy or D2+ lymphadenectomy.The number of lymph node dissected,number of positive lymph nodes,metastatic lymph node ratio were 27± 12,10± 9 and 0.41±0.28,respectively.(2) Follow-up and survival situations:995 patients were followed up for (35± 32)months.During the follow-up,the 1-,3-,5-year overall survival rates were 77.9%,47.8%,36.2%.(3) Prognostic factors analysis after operation:results of univariate analysis showed that sex,tumor histological type,vascular embolus,degree of tumor invasion,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were related factors affecting prognosis of radical gastrectomy for stage Ⅲ gasteric cancer (hazard ratio =0.817,1.486,1.268,2.173,1.957,1.737,3.357,2.169,95% confidence interval:0.686-0.973,1.059-2.086,1.074-1.497,1.195-3.954,1.480-2.588,1.390-2.170,2.476-4.602,1.740-2.704,P<0.05).Results of multivariate analysis showed that sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer (hazard ratio =0.805,1.476,0.237,1.475,3.811,3.600,95% confidence interval:0.673-0.963,1.049-2.087,0.083-0.678,1.140-1.909,2.259-6.428,1.317-9.839,P<0.05).(4) Stratified analysis:of the 995 patients,the postoperative l-,3-,5-year overall survival rates were 93.7%,69.6%,60.5% in the patients with metastatic lymph node ratio ≤ 0.1,86.9%,60.6%,44.3% in the patients with 0.1 < metastatic lymph node ratio ≤0.4 and 64.3%,28.9%,21.0% in the patients with metastatic lymph node ratio > 0.4,showing a statistically significant difference (x2 =121.300,P<0.05).There were statistically significant differences between patients with metastatic lymph node ratio ≤0.1 and patients with 0.1< metastatic lymph node ratio ≤0.4,between patients with metastatic lymph node ratio ≤0.1 and patients with metastatic lymph node ratio >0.4 (x2=7.580,65.320,P<0.05).There was a statistically significant difference between patients with 0.1 < metastatic lymph node ratio ≤0.4 and patients with metastatic lymph node ratio>0.4 (x2 =80.806,P<0.05).① Stratified analysis of tumor pathological N staging:the average metastatic lymph node ratio was 0.09 in the 132 stage N1 patients,who were divided into the patients with metastatic lymph node ratio ≤ 0.1 and > 0.1.The postoperative 1-,3-,5-year overall survival rates were 92.2%,68.6%,59.1% in the 108 patients with metastatic lymph node ratio ≤ 0.1 and 79.2%,32.8%,21.9% in the 24 patients with metastatic lymph node ratio >0.1,respectively,showing a statistically significant difference (x2 =14.499,P<0.05).The average metastatic lymph node ratio was 0.23 in the 265 stage N2 patients,who were divided into the patients with metastatic lymph node ratio ≤0.2 and >0.2.The postoperative 1-,3-,5-year overall survival rates were 92.3%,73.8%,61.0% in the 138 patients with metastatic lymph node ratio ≤0.2 and 76.5%,40.1%,22.2% in the 127 patients with metastatic lymph node ratio >0.2,respectively,showing a statistically significant difference (x2 =42.536,P<0.05).The average metastatic lymph node ratio was 0.56 in the 598 stage N3 patients,who were divided into the patients with metastatic lymph node ratio ≤0.4 and >0.4.The postoperative 1-,3-,5-year overall survival rates were 88.5%,62.8%,47.0% in the 194 patients with metastatic lymph node ratio ≤ 0.4 and 64.3%,29.8%,21.0% in the 404 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =51.860,P< 0.05).② Stratified analysis of number of lymph node dissected:7 of 117 patients with the number of lymph node dissected < 15 had metastatic lymph node ratio ≤0.1,who were divided into patients with metastatic lymph node ratio ≤0.4 and >0.4.The postoperative 1-,3-,5-year overall survival rates were 78.2%,40.0%,28.6% in the 44 patients with metastatic lymph node ratio ≤0.4 and 78.1%,18.7%,12.9% in the 73 patients with metastatic lymph node ratio>0.4,respectively,showing a statistically significant difference (x2 =4.727,P<0.05).③ Stratified analysis of tumor pathological TNM staging:of 262 patients with stage Ⅲa gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 88.5%,65.0%,54.3% in the 230 patients with metastatic lymph node ratio ≤0.4 and 77.5%,35.4%,29.5% in the 32 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =6.132,P<0.05).Of 296 patients with stage Ⅲb gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.4%,60.7%,42.7% in the 200 patients with metastatic lymph node ratio ≤ 0.4 and 59.9%,26.8%,21.7% in the 96 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =23.699,P<0.05).Of 437 patients with stage Ⅲ c gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.7%,59.9%,38.7% in the 133 patients with metastatic lymph node ratio ≤0.4 and 64.0%,27.9%,18.3% in the 304 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2=36.215,P< 0.05).(5) ROC curve:ROC curves of postoperative overall survival rates in patients with stage Ⅲ gastric cancer were drawn using the number of positive lymph nodes and metastatic lymph node ratio,of which AUC were 0.619 (95% confidence interval:O.588-0.649) and 0.706 (95% confidence interval:0.677-0.734),showing a statistically significant difference (Z=8.842,P<0.05).Conclusions Sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging are independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer.There is different prognosis of patients with different metastatic lymph node ratios in the subgroup of the same tumor pathological TNM staging,number of lymph node dissected,tumor pathological TNM staging.Compared with tumor pathological N staging,metastatic lymph node ratio has a more accurate predictive value for prognosis.
10.The expression and clinical significance of S100A9 protein in gastric cancer of intestinal type
Rongjian ZHOU ; Heng ZHANG ; Ping SHU ; Hongshan WANG ; Zhenbin SHEN ; Fenglin LIU ; Jing QIN
Chinese Journal of General Surgery 2019;34(1):53-57
Objective To investigate the expression and clinical significance of pro-inflammation S100A9 protein in intestinal type gastric cancer.Methods We retrospectively analyzed the clinicopathological materials of the 278 patients who were diagnosed as Lauren classification intestinal gastric cancer and underwent surgical treatment between January and December 2008 at the Department of General Surgery,Zhongshan Hospital Fudan University.Immunohistochemistry was used to analyze the expression of S100A9 protein in tumor tissues and para-tumor tissues.Results High expression of S100A9 protein was associated with the depth of tumor invasion (P =0.013),lymph node metastasis (81.4%,53.9%,47.3% vs.84.7%,69.3%,60.7%,x2 =4.220,P =0.041) and TNM stage (P =0.010).The overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.In stage Ⅲ/Ⅳ patients,the overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.Moreover,for those patients who received postoperative chemotherapy,the prognosis of the patients with high expression of S100A9 protein was poorer than those with low expression.By multivariable analysis,the expression of S100A9 protein was not an independent risk factor for the prognosis of intestinal gastric cancer patients.Conclusions High expression of S100A9 protein in intestinal gastric cancer was associated with poor prognosis.

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