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.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.
3.Advances in pharmacological effects of ginseng,acorus calamus and its couplet medicine on Alzheimer's disease
Yu-Chen ZHU ; Bo-Yu KUANG ; Jin-Ping LIANG ; Xiao-Lei PEI ; Jia-Zhu ZHAO ; Shi-Feng CHU ; Nai-Hong CHEN ; Yan-Tao YANG
Chinese Pharmacological Bulletin 2024;40(5):817-822
The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.
4.Development and evaluation of a triplex RT-qPCR assay with internal references for detection of the Dengue and Zika viruses
Meng-Tao CAO ; Xiao-Yu HU ; Wei YANG ; Chun-Yuan LI ; Xiao-Li XU ; Rui-Wen REN ; Hong-Xia JIANG
Chinese Journal of Zoonoses 2024;40(6):537-543
A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5%.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59%.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.
5.A cross-sectional study of functional disability rate of anxiety disorder and risk factors in Chinese community adults
Yang LI ; Yueqin HUANG ; Zhaorui LIU ; Tingting ZHANG ; Chao MA ; Lingjiang LI ; Yifeng XU ; Tao LI ; Xiufeng XU ; Yaqin YU ; Yongping YAN ; Zhizhong WANG ; Xiangdong XU ; Limin WANG ; Qiang LI ; Guangming XU ; Shuiyuan XIAO
Chinese Mental Health Journal 2024;38(11):929-935
Objective:To describe functional disability rate of anxiety disorders in Chinese community adults and explore related risk factors of functional disability.Methods:To conduct in-depth data analysis on China Mental Health Survey(CMHS).The diagnostic tool for anxiety disorders was the Composite International Diagnostic Inter-view-3.0,according to the Diagnostic and Statistical Manual for Mental Disorders,Fourth Edition(DSM-Ⅳ).The World Health Organization Disability Assessment Schedule,2nd edition,was the functional disability assessment standard for anxiety disorders.Weighted 12-month functional disability rate of DSM-Ⅳ anxiety disorder with co-morbidities and only anxiety disorder in population and those in patients,as well as days of partial disability were calculated.The effects of anxiety disorders comorbid other mental disorders and physical diseases and demographic factors on the severity and occurrence of functional disability were analyzed by multiple linear regression and logis-tic regression.Results:The functional disability rate of anxiety disorder with comorbidities in population was 1.7%,and 42.2%in patients,in which constituent rate of grade-four disability was the highest as 84.1%.The functional disability rate of only anxiety disorder in population was 0.3%,and 17.8%in patients.The medians of days of partial disability days in the past 30 days were from 0 to 14.42.Multiple linear regression showed a positive association between comorbid anxiety disorder with other mental disorders and physical diseases(β=0.24),comor-bid other mental disorders and physical diseases(β=0.21),physical diseases(β=0.18),comorbid anxiety disor-der and physical diseases(β=0.15),comorbid anxiety disorder with other mental disorders(β=0.08),other men-tal disorders(β=0.07),only anxiety disorder(β=0.06),lower education level(β=0.12),lower economic status(β=0.08),older age(β=0.06),non-marital status(β=0.06),male(β=0.02)and the severity of functional dis-ability.Logistic regression showed that comorbid anxiety with other mental disorders and physical diseases(OR=64.07),comorbid anxiety disorders with other mental disorders(OR=36.75),comorbid other mental disorders with physical diseases(OR=20.60),comorbid anxiety with physical diseases(OR=18.88),anxiety disorder(OR=9.20),other mental disorders(OR=6.65),physical diseases(OR=4.00),65 years old and over(OR=4.40),50 to 64 years old(OR=2.33),low economic status(OR=2.10),illiterate and below primary school educational level(OR=1.89),middle economic status(OR=1.70),elementary school educational level(OR=1.59),non-marital status(OR=1.47),male(OR=1.16)were the risk factors of the occurrence of functional disability.Conclusion:Comorbidity of anxiety disorders and other mental disorders,and physical diseases increases severity and occurrence of functional disability.Comorbidity,male,gender,older age,lower economic and educa-tional level and non-marital are risk factors of anxiety disorder functional disability.
6.A cross-sectional study of disability rate of dementia and risk factors in Chinese old people
Wenlei WU ; Yueqin HUANG ; Zhaorui LIU ; Tingting ZHANG ; Chao MA ; Yifeng XU ; Tao LI ; Xiufeng XU ; Yaqin YU ; Yongping YAN ; Zhizhong WANG ; Xiangdong XU ; Limin WANG ; Qiang LI ; Guangming XU ; Shuiyuan XIAO ; Lingjiang LI
Chinese Mental Health Journal 2024;38(11):936-942
Objective:To describe disability rates of dementia in community residents aged 65 years and over in China,and explore related risk factors of disability.Methods:This study conducted an in-depth data analysis of the China Mental Health Survey.World Health Organization Disability Assessment Schedule 2.0(WHODAS 2.0)was used to assess dementia disability,Community Screening Interview for Dementia(CSID)and Geriatric Mental Status Examination(GMS)were used for dementia screening and diagnosing.Univariate analysis was used to calcu-late the weighted disability rates of dementia in population and in patients,and their population distribution.Multiple linear regression and logistic regression were used to analyze the risk factors of the occurrence of dementia disability and its severity.Results:The weighted disability rate of dementia was 2.1%in population,and 38.6%in pa-tients.The disability rates of comorbid dementia in population and in patients were higher than those of patients with only dementia.Female,older age,lower education level,lower economic status,and lower cognitive test scores in CSID had higher disability rates of dementia in population.Female and urban resident had higher disability rates of dementia in patients.Multiple linear regression showed economic status(β=0.11),gender(β=0.11),age(β=0.10),and treatment in the last 12 months(β=-0.20)were statistically associated with WHODAS 2.0 scores.Multiple logistic regression showed female(OR=2.81)and treatment in the last 12 months(OR=2.38)were statistically associated with disability.Conclusions:Persons with low economic status,female and elderly peo-ple are the high-risk groups for dementia disability.It should be paid attention to prevent dementia and its conse-quential disabilities.
7.Comprehensive therapy of traditional Chinese medicine for erectile dysfunction with damp-heat stasis:A clinical observation of 103 cases
Jun-Chao YAO ; Bao-Jun JU ; Xiao LI ; Lu-Yu LI ; Miao-Miao MA ; Yong-Tao ZHANG
National Journal of Andrology 2024;30(3):233-240
Objective:To assess the clinical effect and safety of comprehensive therapy of traditional Chinese medicine(TCM)in the treatment of erectile dysfunction(ED)with damp-heat stasis.Methods:We selected 108 cases of ED with damp-heat stasis meeting the inclusion criteria and treated with tadalafil(the control group,n=54)or tadalafil+comprehensive TCM therapy(the trial group,n=54)in the First Affiliated Hospital of Henan University of Chinese Medicine in the same period.After 8 weeks of treatment,we recorded the patients'scores on IIEF-5,TCM syndrome,erectile quality(EQS),9-Item Patient Health Questionnaire(PHQ-9)and Generalized Anxiety Scale 7(GAD-7).At 16 weeks of our study,we collected the efficacy parameters,safety indicators and adverse reactions by telephone follow-up and compared the data obtained between the two groups of patients.Results:Totally,103 of the patients completed the study,51 in the control and 52 in the trial group.Compared with the baseline,the IIEF-5 and EQS scores were both markedly increased after 8 weeks of treatment in the trial group(12.35±3.00 vs 18.36±2.82,P<0.05;39.5[30.25-43]vs 67.5[54.5-76.75],P<0.05)and the control(11.96±2.79 vs 15.88±3.86,P<0.05;38.0[29-42]vs 56[49-64],P<0.05),even more significantly in the former than in the latter(P<0.05);the TCM syndrome and GAD-7 scores were remarkably decreased in the trial(9.5[8-12]vs 4.0[2.25-5],P<0.05;5[2.25-6.75]vs 2.5[1-4.75],P<0.05)and the control group(10.0[8-12]vs 5.0[3-6],P<0.05;5.0[3-6]vs 4.0[2-5],P<0.05),even more signif-icantly in the former than in the latter(P<0.05),so were the PHQ-9 scores(P<0.05),but with no statistically significant differ-ence between the two groups(P>0.05).The IIEF-5 scores of the two groups remained significantly higher than the baseline during the follow-up(P<0.05),even higher in the trial than in the control group(17.04±2.60 vs 14.16±3.34,P<0.05).No obvious abnormal safety indicators or adverse events were observed during the study.Conclusion:Comprehensive TCM therapy combined with tadalafil is superior to tadalafil alone in the treatment of ED with damp-heat stasis,and has a better long-term efficacy and a higher safety.
8.Effect and safety of electroacupuncture in the treatment of chronic prostatitis/chronic pelvic pain syndrome:A systematic review and meta-analysis of 17 randomized controlled trials
Jun-Tao LI ; Lu-Yu LI ; Xiao LI ; Feng LIU ; Miao-Miao MA ; Bao-Jun JU
National Journal of Andrology 2024;30(10):921-930
Objective:To systematically evaluate the effect and safety of electroacupuncture in the treatment of chronic prostati-tis/chronic pelvic pain syndrome(CP/CPPS).Methods:We searched the major Chinese and English databases of CNKI,Wan-fang Data,VIP,CBM,PubMed,Cochrane Library,Web of Science and Embase for randomized controlled trials(RCT)on electroa-cupuncture or combination therapy in the treatment of CP/CPPS published from the establishment of the databases to August 2024.The dichotomous data and continuous data were represented by risk ratio(RR)and mean difference(MD)respectively,both with 95%confidence interval(CI).We analyzed the data with the Revman(v.5.4)software and assessed the quality of the evidence in each RCT using the Grading of Recommendations Assessment,Development and Evaluation system(GRADE).Results:Totally 17 RCTs were identified,involving 1 404 cases of CP/CPPS treated by electroacupuncture or combination of electroacupuncture with medication or with other therapies(the trial group)or by medication with Western or Chinese drugs alone(the control group).Compared with the control group,the trial group showed a significantly higher rate of clinical effectiveness(RR=1.25;95%CI:1.18-1.32;P<0.05),decreased CPSI scores(MD=-4.56;95%CI:-5.01--4.11;P<0.05),improved CPSI-pain,-urination and-quali-ty of life scores,and increased maximum and average urinary flow rates.And electroacupuncture did not increase the likelihood of ad-verse reactions.Conclusion:Medium-quality evidence suggests that electroacupuncture is beneficial complementary and alternative therapy for CP/CPPS,with a significant advantage in improving the NIH-CPSI scores of the patients.However,more high-quality multi-centered RCTs with larger sample sizes are still needed to further verify the effect of electroacupuncture on CP/CPPS.
9.Diagnostic performance of PI-RADS v2.1 for clinically significant prostate cancer in the peripheral,transitional and multiple zones
Xiao-Jun DENG ; Hao-Cheng ZHANG ; Jiong ZHANG ; Yu-Hang QIAN ; Mei-Mei TAO ; Chun-Mei LIAO ; Miao-Wen LIN ; Gen-Qiang LANG
National Journal of Andrology 2024;30(11):982-986
Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11%)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74%)of the 47 PZ lesions,8(47.06%)of the 17 TZ le-sions,and 40(90.91%)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P<0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8%,57.6%and 62.1%,and sensitivities of 57.2%,78.4%and 93.2%,respectively.The negative predictive values were 46.5%,85.7%and 79.2%,and the positive predictive values 76.2%,43.4%and 84.8%,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.
10.An artificial intelligence system based on multi-modal endoscopic images for the diagnosis of gastric neoplasms (with video)
Xiao TAO ; Lianlian WU ; Hongliu DU ; Zehua DONG ; Honggang YU
Chinese Journal of Digestive Endoscopy 2024;41(9):690-696
Objective:To develop an artificial intelligence model based on multi-modal endoscopic images for identifying gastric neoplasms and to compare its diagnostic efficacy with traditional models and endoscopists.Methods:A total of 3 267 images of gastric neoplasms and non-neoplastic lesions under white light (WL) endoscopy and weak magnification (WM) endoscopy from 463 patients at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from March 2018 to December 2019 were utilized. Two single-modal models (WL model and WM model) were constructed based on WL and WM images separately. WL and WM images of corresponding lesions were combined into image pairs for creating a multi-modal (MM) characteristics integration model. A test set consisting of 696 images of 102 lesions from 97 patients from March 2020 to March 2021 was used to compare the diagnostic efficacy of the single-modal models and a multi-modal model for gastric neoplastic lesions at both the image and the lesion levels. Additionally, video clips of 80 lesions from 80 patients from January 2022 to June 2022 were employed to compare diagnostic efficacy of the WM model, the MM model and 7 endoscopists at the lesion level for gastric neoplasms.Results:In the image test set, the sensitivity and accuracy of MM model were 84.96% (576/678), and 86.89% (1 220/1 289), respectively, for diagnosing gastric neoplasms at the image level, which were superior to 63.13% (113/179) and 80.59% (353/438) of WM model ( χ2=42.81, P<0.001; χ2=10.33, P=0.001), and also better than those of WL model [70.47% (74/105), χ2=13.52, P<0.001; 67.82% (175/258), χ2=57.27, P<0.001]. The MM model showed a sensitivity of 87.50% (28/32), a specificity of 88.57% (62/70), and an accuracy of 88.24% (90/102) at the lesion level. The specificity ( χ2=22.99, P<0.001) and accuracy ( χ2=19.06, P<0.001) were significantly higher than those of WL model; however, there was no significant difference compared with those of the WM model ( P>0.05). In the video test, the sensitivity, specificity and accuracy of the MM model at the lesion level were 95.00% (19/20), 93.33% (56/60) and 93.75% (75/80). These results were significantly better than those of endoscopists, who had a sensitivity of 77.14% (108/140), a specificity of 79.29% (333/420), and an accuracy of 78.75% (441/560), with significant differences ( χ2=18.62, P<0.001; χ2=35.07, P<0.001; χ2=53.12, P<0.001), and was higher than the sensitivity of advanced endoscopists [83.33% (50/60)] with significant difference ( χ2=4.23, P=0.040). Conclusion:The artificial intelligence model based on multi-modal endoscopic images for the diagnosis of gastric neoplasms shows high efficacy in both image and video test sets, outperforming the average diagnostic performance of endoscopists in the video test.

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