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.Efficacy and safety of different applications of tranexamic acid in high tibial osteotomy
Changling DU ; Hui SHI ; Shoutao ZHANG ; Tao MENG ; Dong LIU ; Jian LI ; Heng CAO ; Chuang XU
Chinese Journal of Tissue Engineering Research 2024;28(9):1409-1413
BACKGROUND:High tibial osteotomy results in massive blood loss during the perioperative period.Tranexamic acid can effectively reduce perioperative blood loss.However,the method of tranexamic acid application has not been unified. OBJECTIVE:To investigate the effect and safety of different methods of tranexamic acid on perioperative blood loss in the high tibial osteotomy. METHODS:A total of 160 patients who underwent primary unilateral high tibial osteotomy in the Binzhou Medical University Hospital from January 2019 to December 2021,including 69 males and 91 females,were randomly divided into four groups(n=40 per group).Among them,40 patients were given an intravenous infusion of saline containing 2 g tranexamic acid 10 minutes before tourniquet release(venous group);40 patients were given an intravenous infusion of 1 g tranexamic acid and 1 g tranexamic acid was injected through a drainage tube after the closure of the incision(combined group);40 patients were given 2 g tranexamic acid infusion into drainage tube after the closure of the incision(perfusion group);an additional 40 patients were given an intravenous infusion of the same amount of normal saline(blank group).The general information was compared among the four groups of patients.The hemoglobin,hematocrit,intraoperative blood loss,drainage volume,blood transfusion rate,incision complication,and the incidence of deep vein thrombosis were recorded on days 1,3 and 5 after operation in the four groups.The total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in general information among the four groups.(2)No significant difference was found in intraoperative blood loss among the four groups.(3)The maximum decreased values of hemoglobin and hematocrit on days 1,3 and 5 after operation,drainage volume,total blood loss and hidden blood loss were all ranked as the combined group
3.Age-, period- and cohort-specific incidence of sexually transmitted diseases in Yantian District from 2008 to 2022
LIN Kai ; LIU Yawen ; LUO Shili ; LI Heng ; LI Xuemei
Journal of Preventive Medicine 2024;36(7):584-589
Objective:
To investigate the incidence trend of sexually transmitted diseases (STDs) in Yantian District, Shenzhen City, Guangdong Province from 2008 to 2022, and the effects of age, period, and cohort on STDs incidence, so as to provide the basis for formulating control measures for STDs.
Methods:
Data of reported STDs cases (syphilis, gonorrhea, genital Chlamydia trachomatis infections, condyloma acuminatum and genital herpes) among population aged 15 to 64 years in Yantian District from 2008 to 2022 were collected through the Chinese Disease Control and Prevention Information System. The temporal and population distribution of STDs were descriptively analyzed. Trends in incidence of STDs were analyzed using average annual percent change (AAPC). Impacts of age, period and cohort on the incidence of STDs were analyzed by an age-period-cohort model.
Results:
A total of 6 156 cases of STDs aged 15 to 64 years were reported from 2008 to 2022, and the average annual incidence was 229.92/105. The overall incidence showed an upward trend (AAPC=2.409%, P<0.05), and an upward trend among females (AAPC=5.846%, P<0.05), but the trend was not statistically significant among males (AAPC=0.193%, P>0.05). The incidence of STDs showed an increasing trend followed by a decreasing trend with the increase of age. The incidence trend among males was consistent with the overall population, reaching its peak in the age group of 30 to 34 years (371.04/105), while the incidence among females showed an increasing trend with the increase of age, peaking in the age group of 60 to 64 years (442.15/105). Compared with 2013-2017, the incidence risk of STDs showed an increasing trend in 2018-2022 (RR=1.349, 95%CI: 1.217-1.495). Compared with the birth cohort of 1975-1979, the incidence risk of STDs in 1980-2005 birth cohort showed an increasing trend, with the highest incidence risk in 2000-2004 birth cohort (RR=4.178, 95%CI: 2.717-6.423).
Conclusions
The overall incidence of STDs among residents aged 15 to 64 years in Yantian District from 2008 to 2022 appeared a tendency towards a rise. Age, period and cohort all had impacts on the incidence, with a greater effect among females than males.
4.Serological and molecular biological characteristics of hepatitis B vaccinated donors with asymptomatic chronical infection in Shenzhen
Xianlin YE ; Tong LI ; Ruonan WANG ; Ran LI ; Heng LIU ; Jinfeng ZENG
Chinese Journal of Blood Transfusion 2024;37(1):26-31
【Objective】 To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. 【Methods】 The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. 【Results】 A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P<0.05). 50 out of 61 sequences for S region were obtained. By phylogenetic analysis, there were 46 cases of type B (92%, 46/50, 38 males and 8 females), 4 cases of type C (8%, 4/50, 3 males and 1 female). The high frequency mutations observed in S region were N40S (8/46,17.39%), G44E (7/46,15.22%), Q129H/R(6/46,13.04%), Y161F/S(7/46, 15.22%), V179A(4/46,8.70%), S53L(2/4,50%), C69T(2/4,50%) and I126S/T(2/4,50%), including the immune escape mutations Q129R and T/I126A/N/S/T. 【Conclusion】 Hepatitis B vaccination can significantly reduce the positive rate of HBsAg and increase the safety of blood transfusion. The high frequency immune escape mutations have become a potential risk of blood safety, and need to be further explored.
5.Historical Evolution and Key Information Research on Pediatric Famous Classical Formula Yigongsan
Jiangmin SU ; Jun ZHANG ; Cong GUO ; Anyi ZHAO ; Liang JIANG ; Heng ZHANG ; Jipeng DI ; Sha CHEN ; Li LIU ; Yan LIU ; An LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):205-214
Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty, which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas(The Second Batch of Pediatrics) released by the National Administration of Traditional Chinese Medicine(TCM) in September 2022, and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature, this study conducted herbal textual research on Yigongsan from five aspects, including historical evolution, origin and processing, dosage conversion, usage and preparation methods, and functional application, then formed the key information table of this formula, in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study, it is recommended that Panax ginseng should be removed the basal part of stem(rhizoma), Poria cocos should be removed the peel, Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian(钱), 1 g/slice for ginger, 3 g for each jujube and 300 mL/Zhan(盏), the doses of Ginseng Radix, Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Jujubae Fructus were 1.652, 1.652, 1.652, 1.652, 1.652, 5, 6 g, and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh, add 300 mL of water and decoct to 210 mL for each dose, then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach, and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians, and is often used to treat anorexia, inflammation of the digestive tract, diarrhea and other diseases in children.
6.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.
7.Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation
Yang YI ; Wenzhe LI ; Kefang LIU ; Heng XUE ; Rong YU ; Meng ZHANG ; Yang-Oujie BAO ; Xinyuan LAI ; Jingjing FAN ; Yuxi HUANG ; Jing WANG ; Xiaomeng SHI ; Junhua LI ; Hongping WEI ; Kuanhui XIANG ; Linjie LI ; Rong ZHANG ; Xin ZHAO ; Xue QIAO ; Hang YANG ; Min YE
Journal of Pharmaceutical Analysis 2024;14(1):115-127
Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
8.Comparison of interoperability among the standard systems of Chinese,the United States,European,and Japanese Pharmacopoeias and other standard systems
Xinyi XU ; Zhen LIU ; Leran TAO ; Haoyun SONG ; Dan LI ; Wenli YU ; Guannan WANG ; Heng LI ; Yun WANG ; Zhaopeng YANG
China Pharmacist 2024;27(2):233-241
Objective To provide reference for the optimization and improvement of interoperability between the standard system of the Chinese Pharmacopoeia and other standards.Methods The interoperability of various pharmacopoeia standard systems was compared by searching for citations from the Chinese Pharmacopoeia,the United States Pharmacopoeia-National Formulary,the European Pharmacopoeia,the Japanese Pharmacopoeia,and other standards,including references to domestic regulations and guidelines,standards of the International Organization for Standardization,guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use,documents of the World Health Organization,and standards from other countries and international organizations.Results In recent years,pharmacopoeias in the world had continuously increased the citation of non pharmacopoeial standards.The types,quantities,and fields of the United States Pharmacopoeia-National Formulary referencing other standards far exceed those of other pharmacopoeias.The Chinese Pharmacopoeia cites the least number of other standards.Conclusion It is suggested that the Chinese Pharmacopoeia should enhance the interoperability with other standard systems in the standards of various professional fields,enhance the openness,harmonization and advantages,and form a more complete standard system.
9.The influencing factors of intracranial hemorrhage in elderly patients with acute occlusion of intracranial arteries after treatment and reperfusion
Lin WANG ; Hongbo HUO ; Zhenghu XU ; Kejing LI ; Heng WANG ; Cuicui LIU
Journal of Chinese Physician 2024;26(1):82-86
Objective:To explore the influencing factors of intracranial hemorrhage in elderly patients with acute occlusion of intracranial arteries after treatment and reperfusion.Methods:A retrospective selection was conducted on elderly patients with acute occlusion of the intracranial artery who were treated at the Hebei Petro China Central Hospital from February 2019 to May 2021. Sixty patients who received mechanical thrombectomy treatment were selected as the observation group, and 60 patients who received combined arterial and venous thrombolysis treatment were selected as the control group. The vascular reperfusion rate and incidence of intracranial hemorrhage were observed and compared between the two groups. Meanwhile, multiple logistic regression analysis was used to identify the influencing factors of intracranial hemorrhage.Results:The reperfusion rate of the observation group′s blood vessels was 85.00%(51/60), significantly higher than the control group′s 68.33%(41/60), and the difference was statistically significant (χ 2=4.658, P=0.031). The National Institutes of Health Neurological Deficit Score (NIHSS) of the observation group after treatment was (10.57±2.23), significantly lower than that of the control group (14.73±2.84), and the difference was statistically significant ( P<0.05). The reperfusion rate of blood vessels in patients under 80 years old in the observation group was significantly higher than that in patients ≥80 years old ( P<0.05). The results of univariate analysis showed that there were statistically significant differences in age, NIHSS at admission, Alberta Stroke Program Early CT Score (ASPECTS), and neutrophil absolute value/lymphocyte ratio (NLR) between patients with and without intracranial hemorrhage (all P<0.05); Multivariate logistic regression analysis showed that age ( OR=1.756, 95% CI: 1.184-2.604) and NIHSS at admission ( OR=2.392, 95% CI: 1.401-4.084) were risk factors for postoperative intracranial hemorrhage in elderly patients with acute occlusion of the large intracranial artery, while ASPECTS ( OR=0.364, 95% CI: 0.190-0.697) was a protective factor. Conclusions:Mechanical thrombectomy has good clinical efficacy in the treatment of elderly patients with acute occlusion of intracranial arteries, and is worthy of clinical use; The intracranial hemorrhage after reperfusion is mainly influenced by the patient′s age, NIHSS at admission, and ASPECTS.
10. Safety of G-CSF in patients with COVID-19
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):334-338
COVID-19, a disease caused by SARSCoV-2 infection, has caused a global pandemic in a short time. The key immunopathological features of COVID-19 include lymphopenia, neutropenia, cytokine storm and related Immune damage to parenchymal organs such as lung. Granulocyte colony stimulating factor (G-CSF) can cause excessive inflammatory reaction, which may aggravate the condition of some patients. Therefore, it is controversial whether COVID-19 should be treated with G-CSF, and clinicians need to evaluate the effectiveness and safety of G-CSF according to the specific conditions of each patient.


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