1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Research status of traditional Chinese medicine regulating oxidative stress to prevent and treat diabetic kidney disease
Xiao-long MEI ; Kun ZHANG ; LI-hui FAN ; Lu-mei ZHANG ; Xia YANG ; Zhi-gang WANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):127-131
Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.
3.A retrospective study of BRAF inhibitors and EGFR inhibitors combined with immune checkpoint inhibitors in patients with microsatellite stable, BRAF V600E mutated metastatic colorectal cancer
Zhi JI ; Jinguo MA ; Xia WANG ; Jiaqi XIN ; Lijun MA ; Yixuan WANG ; Nan ZHANG ; Chunyan ZENG ; Rui LIU
Chinese Journal of Oncology 2025;47(9):922-928
Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.
4.Application of ropivacaine combined with dezocine in painless delivery of primiparas with epidural anesthesia
Dong-dong YANG ; Xiao-yi GONG ; Yun-zhi LING ; Ya-xiang WANG ; Mei SUN ; Rui DUAN ; Xia YE ; Ya ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(6):535-539
Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.
5.Construction of A Mouse Model of Liver Cancer Resistant to PD-1 Monoclonal Antibody and Analysis of Its Metabolic Changes
Xin-ru NIU ; Xia WANG ; Zhi-ting SHU ; Zi-lan XU ; Xiao-li QIU ; Wei DAI ; Liang-qian ZHANG ; Xiang-liang DENG
Progress in Modern Biomedicine 2025;25(12):1931-1941,1954
Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50%.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.
6.Development and application of pilot hypoxia endurance testing system
Lin-xia LI ; Guo-yun MAO ; Ming-rui HU ; Jia-ling XU ; Yao-xuan JI ; Na ZHI ; Yan-qing BAI ; Yun-ying WANG
Chinese Medical Equipment Journal 2025;46(10):23-28
Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]
7.Establishment of a rapid fluorescence immunochromatographic assay for avian influenza virus subtype H5N6
Hui LI ; Li LIU ; Yi-sheng ZHOU ; Zhi-hong ZHANG ; Qian-qian SI ; Ru-xia WANG ; Zhi-qiang DENG ; Yi-bing FAN ; Liang JIN ; Jie SUN ; Chun-hua YANG
Chinese Journal of Zoonoses 2025;41(3):243-248,283
In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.
8.FRMD4A promotes autophagy in placental trophoblast cells in preeclampsia
Wen-xia LI ; Xiao-ye WANG ; Zhi-hui LI ; Li-juan HUANG ; Ke-ping QIANG ; Qi-peng ZHAO ; Yan-hua WANG
Chinese Pharmacological Bulletin 2025;41(12):2268-2274
Aim To investigate the role of FRMD4A in autophagy of placental trophoblast cells in preeclampsia(PE).Methods The placental tissues and clinical data of normal pregnancy and PE were obtained,and the histopathological changes were observed by HE staining.An in vitro model of hypoxia-induced HTR-8/SVneo trophoblast cells was established.The expres-sions of LC3B Ⅱ/Ⅰ and p62 in placental tissues and hypoxic cell models were analyzed by Western blot.The expression of FRMD4A was detected by qRT-PCR,Western blot and immunofluorescence,and the correlation between the expression level of FRMD4A and the clinical characteristics of the subjects was ana-lyzed by Pearson correlation analysis.Hypoxia induced trophoblast cells were transfected with si-FRMD4A,and the expression of LC3 B Ⅱ/Ⅰ and p62 was analyzed by Western blot.Results Compared with the normal group,the expression of LC3B Ⅱ/Ⅰ in PE placental tissues and hypoxia-induced trophoblast models was significantly upregulated,while the expression of p62 was significantly downregulated.Meanwhile,the ex-pression of FRMD4A increased significantly.Moreo-ver,its expression was positively correlated with the maternal systolic blood pressure,diastolic blood pres-sure,and platelet count,but negatively correlated with the neonatal weight(P<0.01).In addition,hypoxia-induced trophoblast cells transfected with si-FRMD4A showed a significant decrease in LC3B Ⅱ/Ⅰ and an increase in p62 expression.Conclusions The expres-sion of FRMD4A is upregulated in PE placenta and hy-poxia-induced trophoblast cell model.Interfering with it can significantly hinder the autophagy process of trophoblast cells,suggesting that it may serve as a po-tential molecular target to participate in the pathologi-cal process of PE.
9.Effects of TREM2 on synaptic plasticity induced by cocaine addiction
Rui-ke XU ; Zhi-wen WANG ; Jiao-jiao OUYANG ; Qi DU ; Li-hua LI ; Shi-jun HONG ; Yan-xia PENG ; Gen-meng YANG
Chinese Pharmacological Bulletin 2025;41(12):2341-2347
Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.
10.Feasibility and exploration of optimal communication models for robot-assisted urological telesurgery: a multicenter, single-arm, retrospective study
Ye WANG ; Taoping SHI ; Sheng TAI ; Sunyi YE ; Yubai ZHANG ; Bingzhang QIAO ; Chenfeng WANG ; Gen CHENG ; Zhi LI ; Qing AI ; Qingbo HUANG ; Baojun WANG ; Qing YUAN ; Junnan XU ; Guojun LIU ; Yu CHEN ; Wuyi ZHAO ; Jianle MAO ; Shiwei LI ; Shuo WANG ; Dan XIA ; Wanhai XU ; Chaozhao LIANG ; Hongzhao LI ; Xin MA ; Xu ZHANG
Chinese Journal of Urology 2025;46(5):331-336
Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter,single-arm,retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients,47 were male(79.7%)and 12 were female(20.3%),with a median age of 63.0(56.0,68.0)years and a body mass index of(24.7 ± 3.0)kg/m 2. Surgical procedures included 32 radical prostatectomies,24 partial nephrectomies,one radical nephrectomy,one adrenalectomy,and one ureteral reconstruction. The perioperative indicators,pathological results and postoperative complications were analyzed. The network monitoring data were collected,and the perioperative data of patients,remote system monitoring data and costs were compared between the two communication modes of optical transport network(OTN)and cloud-connect network(CCN). Results:All 59 remote surgeries were successfully completed,with a mean operative time of(138.0 ± 54.0)minutes,median intraoperative blood loss of 50.0(30.0,100.0)ml and a postoperative hospital stay of 5.0(4.0,6.0)days. No cases required reoperation,Clavien-Dindo grade ≥3 complications,or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing:the shortest latency time(Hefei-Hangzhou,450 km)was(16.59 ± 0.80)ms,while the longest(Harbin-Hangzhou,2 200 km)latency time was(53.31 ± 0.31)ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time[(130.7 ± 70.5)minutes vs.(142.1 ± 42.9)minutes, P = 0.442],postoperative hospitalization[6.0(4.0,8.0)d vs. 5.0(4.0,6.0)d, P = 0.581],or readmission rates(0 vs. 0). However,CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode,with its cost-effectiveness,excellent usability,and multi-point interconnection flexibility,is currently the preferred communication model for telesurgical applications.

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