1.High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling
Ting DUAN ; Zhen ZHANG ; Jinran SHI ; Linyu XIAO ; Jingjing YANG ; Lixia YIN ; Xiaofeng ZHANG ; Zhijun GENG ; Guoyu LU
Journal of Southern Medical University 2024;44(1):129-137
Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.
2.High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling
Ting DUAN ; Zhen ZHANG ; Jinran SHI ; Linyu XIAO ; Jingjing YANG ; Lixia YIN ; Xiaofeng ZHANG ; Zhijun GENG ; Guoyu LU
Journal of Southern Medical University 2024;44(1):129-137
Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.
3.Isongifolene Improves Crohn's Disease-Like Colitis in Mice by Reducing Apoptosis of Intestinal Epithelial Cells
Ting DUAN ; Zhijun GENG ; Jingjing YANG ; Lixia YIN ; Mingxi SUN ; Shunyin WANG ; Xiaofeng ZHANG ; Jing LI ; Jianguo HU ; Guoyu LU
Journal of Sichuan University (Medical Sciences) 2024;55(5):1175-1185
Objective To investigate the effect and molecular mechanism of isolongifolene(ISO)on the apoptosis of intestinal epithelial cells and 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced Crohn's disease(CD)-like colitis in mice.Methods In the animal experiments,mice were randomly assigned to the wild type(WT)group,TNBS group and TNBS+ISO group,with 8 mice in each group.Colitis models of mice were established in the TNBS group and the TNBS+ISO group by rectal injection of TNBS.After modeling,the mice in the TNBS+ISO group were given ISO intervention via intragastric gavage(10 mg/kg),and the other two groups were given the same amount of normal saline via intragastric gavage.The mice were sacrificed on the 7th day.The changes in body mass,disease activity scores(DAI),and the colon length of mice were measured,and transepithelial electrical resistance(TEER)of the colon tissues was determined.The score of colon inflammation was calculated according to HE staining.The levels of intestinal mucosal inflammatory factors,including tumor necrosis factor alpha(TNF-α),interferon(IFN)-γ,interleukin(IL)-1 β,and IL-6,were measured by RT-PCR and ELISA.The apoptosis of colon tissue cells was determined by TUNEL assay.The expressions of apoptotic proteins(cleaved caspase-3/caspase-3 and Bax),an anti-apoptotic protein(Bcl-2),and tight junction proteins(ZO-1 and claudin-1)were detected by Western blot and immunofluorescence.In the cell experiment,TNF-α was used to induce intestinal epithelial cell Caco-2 apoptosis model,which was treated with ISO.Then,intervention with the AMPK inhibitor Compound C was given.TUNEL assay,Western blot assay,and immunofluorescence assay were performed to measure apoptosis and the expression of apoptosis proteins in the Caco-2 cells.Gene Ontology(GO)enrichment analysis was performed to predict the biological function of ISO.Then,the mechanism involved was verified by examination of the mice and Caco-2 cells.Western blot was performed to determine the expression levels of p-AMPK/AMPK and p-PGC1α in the colon tissues from the mice of different groups and Caco-2 cells.The apoptosis of the cells was determined by TUNEL assay.Results According to the results of the animal experiment,ISO could alleviate experimental colitis and intestinal barrier dysfunction,leading to improvements in body mass loss,colon length shortening,DAI score,inflammatory rating,and TEER values(all P<0.05)in mice.Furthermore,ISO decreased the expression of pro-inflammatory factors TNF-α,IFN-γ,IL-1β,and IL-6 and increased the expression of the tight junction proteins ZO-1 and claudin-1(all P<0.05).In the cell experiment,in a TNF-α-induced intestinal epithelial cell model,ISO was also found to protect intestinal barrier against damage.ISO reduced the proportion of apoptotic intestinal epithelial cells,reduced the expression of cleaved-caspase-3/caspase-3 and Bax,and upregulated the level of Bcl-2(all P<0.05).GO enrichment predictive analysis showed that the role of ISO in improving CD-like enteritis might be associated with the negative regulation of apoptosis.Verification of the mechanism showed that the expression of p-AMPK and p-PGC1α in the mice colon tissue was significantly upregulated after ISO intervention(P<0.05).In contrast,the AMPK inhibitor Compound C increased the apoptosis rate of ISO-treated Caco-2 cells and decreased the relative expression levels of ZO-1 and claudin-1(P<0.05).Conclusion ISO reduces intestinal epithelial cell apoptosis at least in part by activating AMPK/PGC1α signaling pathway,thereby alleviating TNBS-induced intestinal barrier dysfunction and CD-like colitis in mice.
4.Clinical characteristics of 83 patients with acute glyphosate herbicide poisoning
Baoqian ZHANG ; Ding YUAN ; Yi LI ; Zhigao XU ; Yanwu YU ; Changhua SUN ; Lu CHE ; Guoyu DUAN ; Sujuan LI ; Guiying ZHU ; Jianjun GUO ; Linlin HOU ; Yan ZHANG ; Fang YANG ; Hongyi YAN ; Cuicui MENG ; Yanxia GAO
Chinese Journal of Emergency Medicine 2022;31(3):315-321
Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.
5.Analysis of 43 cases of anti-NMDA receptor encephalitis misdiagnosed as mental disorder
Yanxia GAO ; Yang JING ; Yi LI ; Ding YUAN ; Changju ZHU ; Yibo WANG ; Linlin HOU ; Guoyu DUAN ; Pei SUN ; Jingjing WANG ; Wanwan JIN ; Zhigao XU
Chinese Journal of Emergency Medicine 2021;30(2):208-212
Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.
6.A report on the follow-up of 14 patients with familial thallium poisoning after 9 years
Yanxia GAO ; Pei SUN ; Yi LI ; Ding YUAN ; Ke GAO ; Qingyan XU ; Bo LI ; Li ZHANG ; Guoyu DUAN ; Yibo WANG ; Linlin HOU ; Yan ZHANG ; Tongwen SUN
Chinese Journal of Emergency Medicine 2020;29(3):360-364
Objective:To investigate the recovery of patients with acute thallium poisoning after 9 years.Methods:A group of 14 patients with familial thallium poisoning who were admitted to our hospital in 2010 were followed up for 9 years.Results:Among the 14 patients with acute thallium poisoning, one patient died on the 14th day after poisoning, and all the other survivors were followed up 9 years later. The general condition of all the patients was significantly better than that of poisoning 9 years ago. The alopecia of all cases disappeared, the newborn hair grew normally, without gastrointestinal symptoms, numbness, pain in the limbs and mental symptoms. All the patients returned to normal intelligence and physical strength and had a normal life. One patient (No. 5) gave birth to 2 children successively after discharge. The first child was 6 years old and the second child was 2 years old. Both growth and intelligence were not different from those of the same age. Currently, the third pregnancy was more than 7 months. No.6 and No.10 patients were poisoned in their teenage and were currently all studying in university. No.6 patient suffered from Hashimoto's thyroiditis 7 years after poisoning, and he has been taking thiamazole tablets for two years. Poisoned infants, No.7, 8 ,11 and 12, were school-age children with normal growth, mental development and excellent academic performance. Among the 13 surviving patients, blood and urine samples from No. 1, No. 3, and No. 4 patients were collected, and no thallium concentration was detected, and biochemical examina-tion and neurological examination were all normal.Conclusions:Patients with acute thallium poisoning have a favorable prognosis according to the follow-up after 9 years. All patients have no obvious sequelae and have normal labor ability. Young women have normal fertility, and children have normal growth and mental development.
7.The role of elevated blood amylase in the assessment of diabetic ketoacidosis
Yanxia GAO ; Yanan WANG ; Ding YUAN ; Yibo WANG ; Yi LI ; Linlin HOU ; Pei SUN ; Yan ZHANG ; Guoyu DUAN ; Zhigao XU
Chinese Journal of Emergency Medicine 2020;29(5):707-710
Objective:To investigate therole of serum amylase elevation in the evaluation of diabetic ketoacidosis (DKA) patients and the related factors affecting serum amylase (AMS) levels in patients with diabetic ketoacidosis.Methods:A total of 249 patients with DKA who were admitted to the First Affiliated Hospital of Zhengzhou University from November 2011 to August 2018 were selected for this retrospective study. The patients were divided into the normal group ( n=176) and the elevated group ( n=73) according to the AMS level measured by fasting venous blood samples. The enumeration data such as sex, type of DM, diabetic vascular complications, number of deaths, number of ICU monitoring, and number of acute pancreatitis (AP) after discharge were analyzed by chi-square test or Fisher test, and the measurement data such as age, pH, HbA1c, CO 2CP, Ca 2+, BUN, and Scr were analyzed by independent sample t test to compare the difference between the two groups. Results:The intensive care unit (ICU) monitoring rate was 50.7%, the median length of stay in ICU was 4 days, the median length of hospital stay was 14 days, and the median treatment cost was 28 000 yuan, which were higher in the elevated group than those in the normal group ( P<0.05). There were no significant differences in mortality, AP during hospitalization, and the probability of AP after discharge between the elevated group and the normal group ( P>0.05). The duration of diabetes, the number of previous DKA, the incidence of diabetic vascular complications, HbA1c, pH, BUN, and Scr in the elevated group were all higher than those in the normal group ( P<0.01 or P<0.05). Conclusions:DKA patients with elevated AMS are more likely to be admitted to ICU, and the length of stay in ICU, total length of hospital stay and total cost of treatment are all increased. Where as the overall mortality rate during hospitalization and the likelihood of AP after discharge are not increased.
8.Threshold effects of body mass index on the bone mineral density of Chinese rural women in fluorosis area
Renjie SUN ; Jun MA ; Leizhen DUAN ; Jingyuan ZHU ; Songcheng YU ; Hui HUANG ; Yanli ZHANG ; Guoyu ZHOU ; Chongjian WANG ; Yue BA
Chinese Journal of Preventive Medicine 2020;54(11):1295-1299
To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.
9.Threshold effects of body mass index on the bone mineral density of Chinese rural women in fluorosis area
Renjie SUN ; Jun MA ; Leizhen DUAN ; Jingyuan ZHU ; Songcheng YU ; Hui HUANG ; Yanli ZHANG ; Guoyu ZHOU ; Chongjian WANG ; Yue BA
Chinese Journal of Preventive Medicine 2020;54(11):1295-1299
To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.
10.Prognostic value of procalcitonin in patients with acute paraquat intoxication
Xiaofan ZHANG ; Li LI ; Chao LAN ; Li HUANG ; Guoyu DUAN
Chinese Journal of Emergency Medicine 2016;25(8):1044-1048
Objective To study the prognostic value of procalcitonin (PCT) level in the outcome of patients with paraquat poisoning (PQ).Methods The clinical data of 128 patients with acute PQ admitted to emergency department were collected from March 2013 through March 2014.The patients were divided into two groups:the death group and the survival group (survival of 28 days).Poisoning doses,urine concentration of PQ,time elapsed from poisoning to admission,and time elapsed from poisoning to gastrolavage were documented.And on the 1 st day,the 3rd day and the 7th day after poisoning,serum PCT were detected.The level of PCT was used to investigate the prognostic values in patients with acute PQ in the death group and survival group.Results Of 128 cases,72 (56.3%) survived and 56 died in 28 days.Among them,the level of PCT increased to some extent in the first day in 90 cases,and 48 patients died.According to trend analysis,the levels of PCT in death group on the 1st day,the 3rd day and the 7th day after PQ were significantly higher than those in survival group [ld:(0.96 ±0.13) vs.(0.08 ±0.01),3d:(1.12 ±0.14) vs.(0.28 ±0.05),7d:(1.22 ±0.14) vs.(0.20 ±0.03),P <0.01].There was a trend of escalating PCT levels in death group,whereas the PCT level reached the peak on the 3st day and decreased gradually in the following days in survival group.The early PCT level was obviously related to poisoning doses,urine concentration,CRP,WBC,ALT,CR (the coefficient of association were 0.794,0.723,0.724,0.332,0.700,0.414,respectively,P<0.01).Conclusions The serum level of PCT increased in patients with acute PQ was significantly positively correlated with the oral dose and urine concentration of paraquat,and it can be used as an indicator for PQ severity.There is important clinical significance in detecting the change of serum level of PCT for estimating the condition of patients and evaluating the prognosis.

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