1.Oxidative Stress-related Signaling Pathways and Antioxidant Therapy in Alzheimer’s Disease
Li TANG ; Yun-Long SHEN ; De-Jian PENG ; Tian-Lu RAN ; Zi-Heng PAN ; Xin-Yi ZENG ; Hui LIU
Progress in Biochemistry and Biophysics 2025;52(10):2486-2498
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.
2.Imaging findings of 14 cases of intestinal schwannoma
Yong YU ; Shen-Chu GONG ; Rui-Ting WANG ; Kai HOU ; Xiu-Liang LU ; Li-Heng LIU ; Jian-Jun ZHOU ; Yu-Qin DING
Fudan University Journal of Medical Sciences 2024;51(1):62-68
Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.
3.Rosmarinic acid ameliorates acute liver injury by activating NRF2 and inhibiting ROS/TXNIP/NLRP3 signal pathway
Jun-fu ZHOU ; Xin-yan DAI ; Hui LI ; Yu-juan WANG ; Li-du SHEN ; DU Xiao-bi A ; Shi-ying ZHANG ; Jia-cheng GUO ; Heng-xiu YAN
Acta Pharmaceutica Sinica 2024;59(6):1664-1673
Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through
4.Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children
Heng WANG ; Weihan XU ; Jinrong LIU ; Yun PENG ; Xiaoxia PENG ; Xiaohui WEN ; Xiaolei TANG ; Hui XU ; Hui LIU ; Yuelin SHEN ; Xiaoyan ZHANG ; Haiming YANG ; Yaguang PENG ; Huimin LI ; Shunying ZHAO
Chinese Journal of Pediatrics 2024;62(7):669-675
Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.
5.Development and validation of prognostic nomogram for malignant pleural mesothelioma.
Xiao Jie XIE ; Jian You CHEN ; Jie JIANG ; Hui DUAN ; Yi WU ; Xing Wen ZHANG ; Shen Jie YANG ; Wen ZHAO ; Sha Sha SHEN ; Li WU ; Bo HE ; Ying Ying DING ; Heng LUO ; Si Yun LIU ; Dan HAN
Chinese Journal of Oncology 2023;45(5):415-423
Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans
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Mesothelioma, Malignant
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Prognosis
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Nomograms
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Retrospective Studies
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Proportional Hazards Models
6.Early clinical efficacy of the orthopaedische chirurgie munchen approach to hemiarthroplasty in the treatment of femoral neck fractures in the elderly
Hongquan HENG ; Yuan YANG ; Xuefeng HU ; Mu SHEN ; Guangfei LI ; Peng ZHANG ; Youjia XU ; Jian LI
Chinese Journal of Orthopaedics 2023;43(4):230-237
Objective:To investigate the early clinical outcomes of a minimally invasive anterolateral approach (Orthopadische chirurgie munchen, OCM) versus a conventional (posterolateral approach, PLA) hemiarthroplasty in the treatment of senior femoral neck fractures.Methods:A retrospective analysis was performed on 90 elderly patients with femoral neck fractures who received anterolateral and posterolateral approaches for hemiarthroplasty in the Second Affiliated Hospital of Soochow University from December 2019 to June 2021 and were followed up. In the OCM group, there were 45 cases, including 18 males and 27 females, aged 83.33±5.29 years (range, 76-96 years); In the PLA group, there were 45 cases, including 13 males and 32 females, aged 81.87±5.00 years (range, 75-94 years). Postoperative, surgical indices, perioperative bleeding, and soft tissue injury were assessed; pain was assessed using the visual analogue scale (VAS), and hip function was evaluated using the Harris score and the University of California at Los Angeles (UCLA) score.Results:The incision length, postoperative hospital stay, hemoglobin reduction, and occult blood loss were lower in the OCM group than in the PLA group ( P<0.05), but there was no significant difference in intraoperative bleeding and postoperative transfusion rate ( P>0.05). Serum creatine kinase and C-reactive protein levels (232.98±83.70 IU/L and 81.67±48.85 mg/L) were lower in the OCM group than in the PLA group (296.93±124.58 IU/L and 104.79±36.75 mg/L) 1 day after surgery, and the differences were statistically significant ( t=2.86, P=0.005; t=2.54, P=0.013). Postoperative pain was significantly improved in all patients, and VAS scores were lower in the OCM group than in the PLA group at 12 h, 24 h, and 48 h postoperatively ( P<0.05). The time to get out of bed after surgery was 20.73±4.99 h in the OCM group compared with 41.69±13.58 h in the PLA group, with a statistically significant difference ( t=9.71, P<0.001). Harris scores (63.31±6.21 and 75.76±4.91) and UCLA scores (1.84±0.42 and 3.69±0.76) were higher in the OCM group on the day of discharge and at 1 month postoperatively than in the PLA group (52.69±10.01 and 71.33±3.66); (1.62±0.54 and 3.16±0.80) points, all with statistically significant differences ( P<0.05). However, the differences in Harris score and UCLA score between the two groups at 6 months postoperatively were not statistically significant ( P>0.05). There were two cases of intermuscular vein thrombosis in the OCM group, with a complication rate of 4% (2/45), and one case of dislocation in the PLA group, with a complication rate of 2% (1/45), there was no significant difference between the two groups ( P=1.000). Conclusion:The minimally invasive anterolateral approach is a more ideal procedure for elderly patients with femoral neck fractures undergoing hemiarthroplasty. It has the advantages of a short incision, small soft tissue damage, low occult blood loss, early removal from bed, a short postoperative hospital stay, an improvement in pain, and a good early recovery of hip function.
7.Efficacy of IFN-α2b combined with isotonic glucose in the treatment of acute herpes zoster and its effect on serum inflammatory factors
Qin YIN ; Li-Ping CHEN ; Heng XU ; Yan YUAN ; Dong LIANG ; Wen SHEN
Chinese Journal of Clinical Medicine 2023;30(6):1005-1009
Objective To explore the efficacy of IFN-α2b combined with isotonic glucose in the treatment of acute herpes zoster and its effects on serum inflammatory factors.Methods A total of 88 patients with acute herpes zoster in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2022 were selected perspectively and randomly divided into the group IFN(n=44)and the group C(n=44).All patients received basic drug treatment and paravertebral nerve block.Patients in group C were treated with traditional analgesic solution(lidocaine,mecobalamin and compound betamethasone diluted with normal saline),and patients in group IFN were treated with IFN-α2b diluted with 5%glucose on the basis of traditional analgesic solution.Visual analogue scale(VAS)score,immunoglobulin M(IgM),immunoglobulin A(IgA),interferon(IL)-17,IL-10,C-reactive protein(CRP),effective rate and adverse reactions were compared between the two groups.Results Compared with before treatment,the VAS scores in both groups decreased after treatment(P<0.05),and the VAS scores in group IFN were lower than those in group C at 2,4,8,12 weeks after treatment(P<0.05).Compared with group C,serum IL-17 and CRP decreased(P<0.001)and IL-10,IgM and IgA increased(P<0.001)in group IFN after treatment.Effective rate in group IFN was higher than that in group C(95.45%vs 79.55%,P=0.024)and there was no significant difference in adverse reactions between the two groups.Conclusions The effects of IFN-α2b combined with isotonic glucose nerve block on relieving pain and improving the level of serum inflammatory factors are better than traditional analgesic solution in patients with acute herpes zoster.
8.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
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Female
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Gestational Age
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Humans
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Infant
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Infant, Extremely Premature
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Infant, Newborn
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Pregnancy
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Respiratory Distress Syndrome, Newborn/epidemiology*
;
Retrospective Studies
;
Treatment Outcome
10.Psychological experience of blood donors with blood donation-related vasovagal reaction: a qualitative research
XiaoFei YANG ; Haili MA ; Lei ZHANG ; Heng ZHANG ; Jiankun BAO ; Tao SHEN ; Li JIN ; Shaoe LI
Chinese Journal of Blood Transfusion 2022;35(4):446-449
【Objective】 To explore the psychological experience of blood donors with blood donation-related vasovagal reaction (DRVR), so as to provide basis for improving the quality of blood donation services. 【Methods】 The real experience of 9 DRVR blood donors was analyzed using the phenomenological research method in qualitative research. 【Results】 The occurrence of DRVR caused distinct psychological conflict among blood donor. Blood donors lacked knowledge about blood donation and expected professional evaluation and continuous support. The occurrence of DRVR was an important reason for blood donor lapsing. 【Conclusion】 By resolving the distinct psychological conflicts of DRVR blood donors, establishing DRVR early warning evaluation and feedback system, as well as strengthening the construction of support system, blood collection and supply institutions can create a good humanistic and social environment for sustainable development of voluntary blood donation.

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