1.Pramlintide improves cognitive function in Alzheimer's disease mice through antioxidant stress and PI3K/Akt pathway
Yating LIU ; Jing LU ; Xiangqian FENG ; Dongling WANG ; Qirong LIAO ; Hongyan YANG ; Huadong ZHOU
Journal of Army Medical University 2025;47(16):1862-1871
Objective To investigate the effect of pramlintide,a pancreatic amyloid peptide analog,on learning and memory of Alzheimer's disease(AD)mice through antioxidant stress,and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods The APP/PS1 mice were divided into a pramlintide treatment group(intraperitoneal injection of 0.5 μmol/L per day for 10 weeks)and an AD group(same dose of PBS),with 5 mice in each group.The learning and memory abilities were detected with water maze test,the pathological changes of the hippocampus were observed with HE staining and immunohistochemistry,the morphological characteristics of dendritic spines in hippocampus were observed after Golgi staining,and the ultrastructure of hippocampal neurons was observed through transmission electron microscopy(TEM).The content of malondialdehyde(MDA)and the level of superoxide dismutase(SOD)in the hippocampal tissue were detected by biochemical assay,and the levels of inflammatory factors IL-6,TNF-α and IL-1β were determined with ELISA.Western blotting was applied to measure the expression of PI3K/Akt signaling pathway related proteins in the hippocampus.In the cell experiment,SH-SY5Y cells were added with Aβ 1-42 to establish a cell model of AD.After the cells were treated with pramlintide,the levels of oxidative stress and inflammatory response were detected,and cell apoptosis was detected by immunofluorescence.Results The animal experiments showed that pramlintide treatment resulted in significantly shortened escape latency(P<0.01),increased platform crossings(P<0.01),and prolonged time to exploring hidden platform(P<0.01).In the hippocampal tissue of the pramlintide treatment group,HE staining displayed hippocampal neurons in high density and neat arrangement(P<0.05),immunohistochemical results showed significantly reduced Aβ protein(P<0.01),Golgi staining results demonstrated more dendritic spines(P<0.05),TEM revealed almost intact neuronal mitochondrial structure,with reduced vacuolization and clear and identifiable morphology.When compared with the AD group,the levels of oxidative stress and inflammatory response were decreased(P<0.01),and the relative expression of p-PI3K/PI3K and p-Akt/Akt proteins was increased(P<0.01)in the treatment group.In cell experiments,the levels of oxidative stress and inflammatory response were decreased in AD cell model after pramlintide treatment(P<0.01),and the results of immunofluorescence showed that cell apoptosis was declined(P<0.01).Conclusion Pramlintide can improve the cognitive function,reduce the hippocampal deposition of Aβ,reduce oxidative stress and inflammatory response,alleviate the pathological changes of neuronal ultrastructure,and enhance the expression of PI3K/Akt signaling pathway in AD mice.
2.Clinical study on Huaiqi Huang Granules combined with conventional western medicine therapy for the treatment of Kawasaki disease in children
Meiyan SU ; Dongling FENG ; Suxian DUAN ; Cuizhi WANG
International Journal of Traditional Chinese Medicine 2025;47(9):1231-1235
Objective:To evaluate the clinical efficacy of Huaiqi Huang Granules combined with conventional Western medicine therapy for the treatment of Kawasaki disease in children.Methods:A randomized controlled trial study was conducted. A total of 96 children with Kawasaki disease admitted to Hebei Children's Hospital from August 2022 to July 2024 were selected as the research objects and divided into the observation group and the control group by the random number table method, with 48 cases in each group. The control group received conventional Western medicine treatment on the basis of symptomatic treatment, while the observation group took Huaiqi Huang Granules on the basis of the control group. The treatment for both groups lasted 7 d. TCM symptoms scores of both groups were evaluated. ELISA was used to detect the levels of TNF-α, MCP-4, and IL-8, while fluorescence immunoassay was used to detect the levels of von Willebrand factor (vWF), endothelin-1 (ET-1), and nitric oxide (NO); flow cytometry was used to detect CD4 +, CD3 +, CD8 + levels and calculate CD4 +/CD8 +ratio; adverse reactions were recorded during treatment and clinical efficacy was evaluated. Results:The total effective rate was 93.75% (45/48) in the observation group and 77.08% (37/48) in the control group, with statistical significance ( χ2=5.35, P=0.021). After treatment, the scores of persistent high fever, skin macules, red throat and eyes, and fatigue in the observation group were lower than those in the control group ( t values were 5.66, 5.45, 5.03, and 5.42 respectively, P<0.01). After treatment, the levels of serum TNF-α, MCP-4 and IL-8 in the observation group were lower than those in the control group ( t values were 4.10, 5.97 and 3.82 respectively, P<0.01). After treatment, the levels of serum vWF [(19.43±3.85) μg/L vs. (23.02±4.13) μg/L, t=4.41] and ET-1 [(38.54±5.12) μg/L vs. (43.90±5.26) μg/L, t=5.06] in the observation group were lower than those in the control group ( P<0.01); the level of NO [(81.23±8.44) μg/L vs. (74.42±8.13) μg/L, t=4.03] was higher than that of the control group ( P<0.01); after treatment, the levels of serum CD4 + and CD3 + and the ratio of CD4 +/CD8 + in the observation group were higher than those in the control group ( t values were 4.91, 4.23, and 3.81 respectively, P<0.01); the CD8 + level was lower than that of the control group ( t=4.19, P<0.01). During the treatment period, the incidence of adverse reactions was 10.42% (5/48) in the observation group and 8.33% (4/48) in the control group, without statistical significance ( χ2=0.12, P=0.726). Conclusion:Huaiqi Huang Granules combined with conventional Western medicine therapy can effectively reduce the TCM syndrome score of children with Kawasaki disease, inhibit the levels of inflammatory factors, improve vascular endothelial function, enhance the body's immunity, and have good medication safety.
3.The effect of Bushen Huoxue prescription on proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating circ_0036763/miR-583 axis
Canrong LIANG ; Junjie HE ; Xueyuan ZHU ; Haojian FENG ; Weijun GUO ; Dongling CAI ; Chenghua ZHU ; Xiaofeng CHEN
Journal of Chinese Physician 2024;26(1):63-69
Objective:To explore the possible effects of Bushen Huoxue Formula (the kidney tonifying and blood activating prescription) on the proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating the circ_0036763/miR-583 axis.Methods:Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ0036763 and miR-583 in normal and intervertebral disc degeneration (IDD) nucleus pulposus cells; IDD nucleus pulposus cells were divided into pcDNA group, pcDNA circ_0036763 group, pcDNA circ_0036763+ mimic NC group, and pcDNA circ_0036763+ miR-583 mimic group. qRT-PCR was used to detect the expression levels of circ_0036763 and miR-583 in nucleus pulposus cells in each group, methyl thiazolyl tetrazolium (MTT) was used to detect cell proliferation (A value), and Western blot was used to detect the expression of proliferating cell nuclear antigen (PCNA), collagen Ⅰ, and collagen Ⅱ proteins in nucleus pulposus cells, The dual luciferase assay reported experimental validation of the targeting relationship between circ_0036763 and miR-583. 27 mice were divided into sham surgery group, IDD group, and kidney tonifying and blood activating formula group. IDD models were established in all groups except for the sham surgery group. After successful modeling, the sham surgery group and IDD group were given physiological saline by gavage, while the kidney tonifying and blood activating formula group was given 1.5 g/ml of kidney tonifying and blood activating formula by gavage for 3 consecutive weeks. QRT-PCR was used to detect the expression levels of circ0036763 and miR-583 in the nucleus pulposus cells of mice in each group, MTT was used to detect cell proliferation, and Western blot was used to detect the expression of PCNA, collagen Ⅰ, and collagen Ⅱ proteins.Results:The expression level of circ_0036763 in IDD nucleus pulposus cells decreased, while the expression level of miR-583 increased (all P<0.05); Overexpression of circ_0036763 can promote proliferation and extracellular matrix synthesis of nucleus pulposus cells (all P<0.05); Circ_0036763 targets miR-583 and upregulates miR-583 reversible overexpression. Circ_0036763 enhances the proliferation and extracellular matrix synthesis ability of IDD nucleus pulposus cells. Compared with the sham surgery group, the IDD group showed an increase in collagen Ⅰ protein expression and miR-583 expression levels (all P<0.05), while the cell A value, PCNA and collagen Ⅱ protein expression, and circ_0036763 expression levels decreased (all P<0.05); Compared with the IDD group, the Kidney Tonifying and Blood Activating Formula group showed a decrease in collagen Ⅰ protein expression and miR-583 expression levels (all P<0.05), while the cell A value, PCNA and collagen Ⅱ protein expression, and circ_0036763 expression levels increased (all P<0.05). Conclusions:The kidney tonifying and blood activating formula (Bushen Huoxue) may induce proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating the circ_0036763/miR-583 axis.
4.A prospective randomized multicenter trial for lymphadenectomy in early-stage ovarian cancer: LOVE study
Ting DENG ; Kaijiang LIU ; Liang CHEN ; Xiaojun CHEN ; Hua Wen LI ; Hongyan GUO ; Huijiao ZHANG ; Libing XIANG ; Xin FENG ; Xiaoyu WANG ; Hextan YS NGAN ; Jianguo ZHAO ; Dongling ZOU ; Qing LIU ; Jihong LIU
Journal of Gynecologic Oncology 2023;34(3):e52-
Background:
The Lymphadenectomy in Ovarian Neoplasms (LION) study revealed that systemic lymphadenectomy did not bring survival benefit for advanced ovarian cancer patients with clinically normal lymph nodes and was associated with a higher incidence of operative complications. However, there is no consensus on whether lymphadenectomy has survival benefit or not in early epithelial ovarian cancer (EOC).
Methods
We designed the LOVE study, a multicenter, randomized controlled, phase III trial to compare the efficacy and safety of comprehensive staging surgery with or without lymphadenectomy in stages IA-IIB EOC and fallopian tube carcinomas (FTC). The hypothesis is that the oncological outcomes provided by comprehensive staging surgery without lymphadenectomy are non-inferior to those of conventional completion staging surgery in early-stage EOC and FTC patients who have indications for post-operative adjuvant chemotherapy. Patients assigned to experimental group will undergo comprehensive staging surgery, but lymphadenectomy. Patients assigned to comparative group will undergo completion staging surgery including systematic pelvic and para-aortic lymphadenectomy. All subjects will receive 3–6 cycles of standard adjuvant chemotherapy. Major inclusion criteria are pathologic confirmed stage IA-IIB EOC or FTC, and patients have indications for adjuvant chemotherapy either confirmed by intraoperative fast frozen section or previous pathology after an incomplete staging surgery. Major exclusion criteria are non-epithelial tumors and low-grade serous carcinoma. Patients with severe rectum involvement which lead to partial rectum resection will be excluded. The sample size is 656 subjects. Primary endpoint is disease-free survival.
5.Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai.
Ziyu FU ; Dongguo LIANG ; Wei ZHANG ; Dongling SHI ; Yuhua MA ; Dong WEI ; Junxiang XI ; Sizhe YANG ; Xiaoguang XU ; Di TIAN ; Zhaoqing ZHU ; Mingquan GUO ; Lu JIANG ; Shuting YU ; Shuai WANG ; Fangyin JIANG ; Yun LING ; Shengyue WANG ; Saijuan CHEN ; Feng LIU ; Yun TAN ; Xiaohong FAN
Frontiers of Medicine 2023;17(3):562-575
The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans
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Aged
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Middle Aged
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COVID-19/prevention & control*
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SARS-CoV-2
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Pandemics/prevention & control*
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China/epidemiology*
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Disease Outbreaks/prevention & control*
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Vaccination
6.Clinical characteristics of the 2019 novel coronavirus Omicron variant infected cases
Ying LYU ; Wei YUAN ; Dongling SHI ; Yixin LIAO ; Yingchuan LI ; Ming ZHONG ; Feng LI ; Enqiang MAO ; Yinzhong SHEN ; Jinfu XU ; Yuanlin SONG ; Bijie HU ; Wenhong ZHANG ; Yun LING
Chinese Journal of Infectious Diseases 2022;40(5):257-263
Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.
7.Effect of applying sitting posture corrector on improving reading and writing posture of elementary school students
Yujuan YANG ; Xiaogang FENG ; Chunyan LUO ; Dongling YANG ; Fang OUYANG ; Siqi ZHU ; Shuangxiao QU
Shanghai Journal of Preventive Medicine 2022;34(3):223-226
Objective To evaluate the effect of applying sitting posture corrector on improving reading and writing posture of elementary school students, and provide scientific evidence for prevention and control of myopia in children and adolescents. Methods One elementary school each in urban and suburban areas of Shanghai was selected using a convenience sampling strategy. Furthermore, two classes each in Grade 3 and 4 were selected as the intervention group (282 students were included in the study), and the other two classes each in Grades 3 and 4 were selected as the control group (294 students were included in the study). Students in the intervention group used the sitting posture corrector in the classrooms for 4 months (from September 2020 to January 2021), while those in the control group did not use the sitting posture corrector. Relevant data were collected before and after the intervention through a self-administered questionnaire and visual examination. Statistical analysis was performed using chi-square test and generalized estimating equation. Results Before the intervention, 13.5% (38/282) of students in the intervention group and 12.2% (36/294) in the control group had good reading and writing posture ( χ 2 = 0.195, P >0.659). After the intervention, 18.4% (52/282) of students in the intervention group had good reading and writing posture, which was higher than that (11.2%, 33/294) in the control group ( χ 2=5.957, P =0.015). Before and after the intervention, there was no significant differences in the prevalence of myopia between students in the intervention and control groups (all P >0.05). Generalized estimating equation analysis showed that students in the intervention group were 1.502 times more likely to have good reading and writing posture than those in the control group after the intervention ( P =0.043). Conclusion Applying sitting posture corrector in schools could improve students' reading and writing posture.
8.Relationship between myopia and nutritional status among upper elementary students in Shanghai
Chinese Journal of School Health 2022;43(1):112-116
Objective:
To explore the relationship between myopia and nutritional status among upper elementary students in Shanghai.
Methods:
A stratified cluster sampling method was used to select 5 576 fourth and fifth grade students from 16 districts in Shanghai, vision test, physical examination and questionnaire survey were administered. Two level multivariate Logistic regression and mixed linear models were used to analyze the relationship between myopia, spherical equivalent (SE) and nutritional status.
Results:
The detection rates of overweight and obesity were 17.0%(949) and 18.7%(1 042), respectively. There was a statistical difference in the proportion of the nutritional status in boys and girls( χ 2=210.94, P <0.01), with overweight and obesity in boys higher than those of girls. The overweight boys were more likely to have myopia (univariate analysis: OR=1.23, P =0.04; multivariate analysis: OR=1.21, P =0.06) than the normal weight boy. Overweight students tended to had more negative refractive than those with normal weight in both boys and girls(multivariate analysis, boys: β =-0.19, girls: β=-0.24, P <0.05). Myopia risk and refractive power in obese students showed no statistical difference with normal weight students( P >0.05).
Conclusion
Overweight students have lower SE than the normal weight among upper elementary students of Shanghai, more researches are needed to confirm this finding and to provide theoretical bases for myopia prevention and control.
9.Analysis of liver function injury associated with 2019-nCoV Omicron mutant strains
Wei YUAN ; Ying LYU ; Dongling SHI ; Yixin LIAO ; Feng LI ; Yinzhong SHEN ; Yun LING
Chinese Journal of Hepatology 2022;30(5):513-519
Objective:To investigate the clinical features and influencing factors of liver function injury in patients with 2019-nCoV/SARS-CoV-2 Omicron mutant strains.Methods:1 183 confirmed imported cases of SARS-CoV-2 who were admitted at Shanghai Public Health Clinical Center (affiliated to Fudan University) from July 1, 2021 to January 15, 2022 were collected. Clinical data, viral genotyping and laboratory test results were collected to retrospectively analyze the basic condition and clinical characteristics of liver function injury. Statistical analysis was performed using t-test or Wilcoxon rank-sum test, χ2 test or Fisher's exact test, Pearson correlation test and logistic regression analysis. Results:125 (10.6%) cases had raised baseline ALT level and 60 (5.1%) cases had abnormal baseline AST level. Among them, 33 cases (2.8%) had received hepatoprotective drugs. Liver function injury was generally mild in SARS-CoV-2 infection and minimal in Omicron mutant strains. Leukocyte count was increased in patients with raised alanine aminotransferase (ALT) [(6.96±1.78)×10 9/L vs. (6.41±1.96)×10 9/L, P=0.005 2], CT scan showed the proportion of liver hypodensity was significantly increased (2.4% vs. 0.3%, P=0.018 0). High-sensitivity C-reactive protein [(7.83±22.36) mg/L vs. (2.68±6.21) mg/L, P=0.007 8] and D-dimer [(0.34±0.39) μg/ml vs. (0.31±0.75) μg/ml, P=0.047 5] levels were higher in patients with raised AST than normal group. 26 cases had normal liver function at hospital admission; however, abnormal liver function was occurred during the course of the disease. Another 8 patients had abnormal liver function at hospital admission, and reduced liver function further during the course of treatment. Recovery time and length of hospital stay was significantly affected in patients with worsened liver function. Baseline body mass index value [odds ratio ( OR)]=1.80, P=0.047), non-Omicron strains ( OR=12.63, P=0.046), D-dimer ( OR=2.36, P=0.047) and interleukin-6 levels ( OR=1.03, P=0.009), and those who used glucocorticoids and/or ulinastatin after hospital admission ( OR=6.89, P=0.034) had a higher risk of worsening liver function. Conclusions:Liver dysfunction could be observed among COVID-19 patients. Patients infected with omicron variant generally showed mild liver injury. Dynamic monitoring of liver function is necessary, especially among those with baseline elevated IL-6, D-Dimer level and use of antiinflammation medication during treatment.
10.Analysis of myopia related factors among primary and secondary school students in Shanghai
LUO Chunyan, QI Wenjuan, HE Xiangui, YANG Dongling, WANG Jingjing, YAN Qiong, FENG Xiaogang
Chinese Journal of School Health 2021;42(2):185-189
Objective:
To analyze myopia related factors among students in Shanghai, to explore associated risky behaviors associated with mild, moderate, high myopia,so as to provide the evidence for the implementation of home and school combination intervention measures.
Methods:
Six primary and secondary schools (2 primary schools, 2 middle schools and 2 high schools) were selected from each district of Shanghai. The primary schools began to investigate from the fourth grade. All the students in the selected classes participated in the vision test and questionnaire survey. Chi square test was used for categorical data analysis. The relationship between myopia and related behaviors was analyzed by multivariate Logistic analysis.
Results:
The prevalence of visual-related risky behaviors such as short outdoor time during the day, lack of sleep, long after-school reading and writing time, poor reading and writing posture, and longtime-using mobile electronic screen was higher in girls than in boys (P<0.05), boys were more likely than girls to use computer for long time and read books/electronic screen in sunlight (P<0.05). The group with 3 hours or more than of reading and writing compared with the less than 2 hours, the OR value of mild myopia model was 1.31(1.20-1.44), moderate myopia model was 1.78(1.62-1.96), severe myopia model was 2.37(2.07-2.71). In the model of moderate and high myopia, reading and writing posture, frequency of eye relax, outdoor activity time and watching TV time were also included.
Conclusion
The prevalence of myopia related behaviors among primary and secondary school students is high, and there are significant gender differences among different behaviors. Students reading and writing time should be strictly controlled after school. Intervention strategies and measures should be carried out according to the characteristics of different ages and genders.


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