1.Recommendations for the clinical use of anti-amyloid-β monoclonal antibody for Alzheimer's disease(2025)
Nan ZHI ; Jinwen XIAO ; Rujing REN ; Binyin LI ; Jintao WANG ; Jieli GENG ; Wenwei CAO ; Yaying SONG ; Hualong WANG ; Shuguang CHU ; Guoping PENG ; Jun LIU ; Xiaoyun LIU ; Fang YUAN ; Wen WANG ; Ronghua DOU ; Xia LI ; Ling YUE ; Wenshi WEI ; Xiaoling PAN ; Xiangyang ZHU ; Dian HE ; Weinü FAN ; Jingping SHI ; Nan ZHANG ; Hui ZHAO ; Qin CHEN ; Cuibai WEI ; Xiaochun CHEN ; Gang WANG
Journal of Chongqing Medical University 2025;50(9):1133-1140
In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.
2.Diagnostic value of MS score in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis
Lingling GENG ; Yue PENG ; Duomei SHI ; Li WANG ; Xianyan TANG ; Xinran WEN ; Wenhua ZHANG ; Xiaoqing LI
International Journal of Pediatrics 2025;52(7):476-480
Objective:To explore the diagnostic value of the macrophage activation syndrome/systemic juvenile idiopathic arthritis(MS)score in macrophage activation syndrome(MAS)associated with systemic juvenile idiopathic arthritis(sJIA),and to provide a reference for clinical work.Methods:This study was a retrospective case-control analysis,conducted on the patients initially diagnosed as sJIA-associated with MAS and admitted into the Department of Rheumatology and Immunology of Children's Hospital Affiliated to Xi 'an Jiaotong University from July 1st,2016 to June 30th,2023. All of the patients met the diagnostic criteria for patients with MAS associated with sJIA according to the 2016 European Alliance of Associations for Rheumatology(EULAR)/American College of Rheumatology(ACR)/Pediatric Rheumatology International Trials Organization(PRINTO)standards. The basic information at baseline,clinical manifestations,and auxiliary examination results were collected. The MS score was applied to re-evaluate the children diagnosed as sJIA-associated with MAS. When the MS score ≥-2.1,the possibility of sJIA with MAS was high. Thirty cases of sJIA without MAS were randomly selected as the control group.Results:There were 28 cases in the MAS group,including 13 males(46.43%)and 15 females(53.57%),with an average age of(7.51±4.01)years. Compared with the control group,the MAS group were significantly more likely to have high fever( χ2=8.539, P=0.003),hepatomegaly( χ2=11.621, P<0.001),splenomegaly( χ2=11.710, P<0.001)and neurological involvement( χ2=27.619, P<0.001),with the differences being statistically significant. Meanwhile,there were statistically significant differences between the two groups in terms of white blood cell count( Z=-4.001, P<0.001),neutrophil count( Z=-3.659, P<0.001),platelet count( Z=-4.687, P<0.001),albumin level( Z=-4.018, P<0.001),alanine aminotransferase( Z=-3.846, P<0.001),aspartate aminotransferase( Z=-5.932, P<0.001),lactate dehydrogenase( Z=-6.150, P<0.001),triglycerides( Z=-5.874, P<0.001),fibrinogen( Z=-5.808, P<0.001),ferritin( Z=-5.280, P<0.001),erythrocyte sedimentation rate( Z=-3.971, P<0.001),ferritin/erythrocyte sedimentation rate( Z=-5.433, P<0.001),reduction of two-line cells in blood( χ2=11.408, P<0.001)and the presence of hemophagocytosis in bone marrow smears( χ2=28.260, P<0.001). Moreover,there was a statistically significant difference in MS scores between the two groups( Z=-6.148, P<0.001),with higher MS scores in the MAS group. Nevertheless,this study showed the median MS scores of both groups ≥-2.1. Conclusion:The MS score was significant to a certain degree as reference for the diagnosis of MAS,and this study showed that the MS score in the MAS group was significantly higher than the control group. However,the median MS scores in both groups were no less than -2.1. This might be related to the influence of factors during the assessment,which made it necessary to optimize the cutoff values of the MS score. Therefore,prospective studies should be carried out on the role of MS score in early identification of MAS.
3.Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer.
Shizhen GENG ; Tingting XIANG ; Yaru SHI ; Mengnian CAO ; Danyu WANG ; Jing WANG ; Xinling LI ; Haiwei SONG ; Zhenzhong ZHANG ; Jinjin SHI ; Junjie LIU ; Airong LI ; Ke SUN
Acta Pharmaceutica Sinica B 2025;15(2):1084-1097
Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.
4.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
5.Research on traditional Chinese medicine improving neurodegenerative diseases based on mitochondrial dynamics
Zi-yang ZHAO ; Hao-nan SHI ; Yang GENG ; Lei ZHANG ; Qian-qian FENG ; Yan-yan JIANG ; Shi-fen DONG
Chinese Pharmacological Bulletin 2025;41(2):201-207
Disorders of mitochondrial dynamics are closely re-lated to the development of neurodegenerative diseases(NDDs),which are characterized by the loss of neurons in brain and spinal cord cells.Diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease,and so on are in-volved in NDDs,which are often accompanied by disorders of mi-tochondrial dynamics during the development of these diseases.Recently,the researches on mitochondrial dynamics to study the pathogenesis of neurodegenerative diseases and related medica-tion innovation have garnered significant attention.This review focuses on the fundamental molecular processes of mitochondrial dynamics,such as mitochondrial transport,mitochondrial autoph-agy,and mitochondrial fission-fusion,and their molecular mecha-nisms in the pathogenesis of NDDs.It also outlines the recent research progress on Chinese materia medica and natural prod-ucts in ameliorating NDDs by modulating mitochondrial dynam-ics.The aim is to establish a foundation for researching innova-tive traditional Chinese medicine for NDDs-related diseases by focusing on mitochondrial dynamics.
6.Research progress on mechanism of interferon regulation of JAK/STAT pathway in HIV-1 infection
Qing LI ; Long FENG ; Jingyi ZHANG ; Yuxuan GENG ; Mengyuan SHI ; Qingya LI ; Wentao GUO ; Haiyan ZHANG ; Jiawen LYU
Chinese Journal of Immunology 2025;41(11):2779-2783,2789
Human immunodeficiency virus(HIV)is the pathogen of acquired immune deficiency syndrome(AIDS).The vi-rus is a highly contagious and highly pathogenic disease caused by the virus attacking the human immune system,which remains a ma-jor global public health problem.Interferon(IFN)is a key cytokine with antiviral and cell-regulatory properties,involved in functions such as cell proliferation,innate and adaptive immune responses.The JAK/STAT signaling pathway is a signal transduction pathway stimulated by cytokines that is involved in many important biological processes such as cell proliferation,differentiation,apoptosis,and immune regulation.With the further in-depth research on AIDS,it has been revealed that IFN and the JAK/STAT pathway play crucial roles in the activation and replication of HIV-1 in target cells.This paper summarizes the structure,signal transduction,and regulatory mechanisms of IFN and the JAK/STAT pathway,and explores the mechanism of IFN-regulated JAK/STAT signaling path-way in HIV-1.It is expected to provide new treatment strategies for the clinical treatment of AIDS.
7.Effect of Diltiazem on Blood Concentration of Tacrolimus in Patients with Nephrotic Syndrome
Kuikui GENG ; Lei LAN ; Shengyu ZHANG ; Aizong SHEN ; Wei WU ; Tianlu SHI
Herald of Medicine 2025;44(2):287-292
Objective To analyze the effect of diltiazem on blood concentration of tacrolimus(TAC)retrospectively,and to provide reference for individual administration of tacrolimus in patients with nephrotic syndrome(NS).Methods The patients with NS who were treated in the outpatient/inpatient department of our hospital from January 2018 to December 2022 were collected,and the general information,combined drug use,blood drug concentration and other information of the patients were recorded.The patients were divided into two groups according to whether diltiazem was used or not:TAC group alone and TAC group combined with diltiazem.The effect of diltiazem on tacrolimus concentration was analyzed.Results A total of 45 patients with NS were included in this study,and 21 patients in the TAC group were treated with TAC alone.The mean blood concentration of TAC after medication was(5.77±2.87)ng·mL-1,which reached the effective therapeutic concentration range.The average blood concentration of TAC+Diltiazem group in the 24 patients was(2.90±1.29)ng·mL-1 before combined treatment,and increased to(5.74±2.46)ng·mL-1 after combined with diltiazem,with a growth rate of(127.34±119.57)%.The increase range was from 10%to 288%,and there was significant difference(P<0.05).According to the observation within 6 months after the combination of the two drugs,the average blood concentration of TAC continued to increase,especially in the 5th month after the administration of TAC,and the concentration tended to be stable after 5 months.By compare with the effect of diltiazem dosage on the blood concentration of TAC,90 mg·d-1 and 180 mg·d-1 had little difference in improving the blood concentration of TAC.At the same time,the combination of the two drugs did not cause adverse reactions.Conclusion A daily dose of 90 mg of Diltiazem can significantly increase the TAC blood concentration in patients with NS who cannot reach the effective therapeutic concentration with conventional doses.It can reach the effective clinical therapeutic concentration without increasing the dose of tacrolimus.The combination of the two drugs were generally safe and effective.
8.Epidemiological characteristics of intestinal infectious diseases in China, 2013-2022
Xueying TIAN ; Bojun JIN ; Yue SHI ; Xuedong ZHENG ; Zengqiang KOU ; Yanping ZHANG ; Mengjie GENG
Chinese Journal of Epidemiology 2025;46(5):776-783
Objective:To deeply analyze the epidemiological characteristics and changing trends of intestinal infectious diseases in China, and provide scientific evidence for the prevention and control of intestinal infectious diseases.Methods:The incidence data of notifiable intestinal infectious diseases in China from 2013 to 2022 were collected from China Disease Prevention and Control Information System. Descriptive statistical method was used to analyze the distributions of intestinal infectious diseases in China, and the annual change rate and seasonal index were calculated.Results:During 2013-2022, intestinal infectious diseases were reported nationwide, with the cases accounting for 43.50% of all notifiable infectious disease cases. The average reported incidence rate was 224.50/100 000, showing a decreasing trend year by year (average annual percent change=-6.45%, t=-2.76, P=0.025). The top 5 intestinal infectious diseases were hand foot and mouth disease (HFMD) (130.40/100 000), other infectious diarrhea (80.18/100 000), dysentery (7.45/100 000), acute hemorrhagic conjunctivitis (2.49/100 000) and viral hepatitis E (1.92/100 000). The incidences of dysentery, HFMD, typhoid fever/paratyphoid fever, viral hepatitis A and acute hemorrhagic conjunctivitis all showed decreasing trends year by year (all P<0.05), while the incidences of hepatitis E and other infectious diarrhea showed no significant changes with year (both P>0.05). The incidence of intestinal infectious diseases was high during May to October, with the peak in June. The incidence rate of intestinal infectious diseases was significantly higher in men than in women (all P<0.05). The HFMD, other infectious diarrhea and dysentery cases were mainly children aged 0-5 years, while the cholera, hepatitis A, hepatitis E, typhoid fever/paratyphoid fever and acute hemorrhagic conjunctivitis cases were mainly farmers aged ≥20 years. The annual reported incidence rate of intestinal infectious diseases was higher in southern provinces (283.66/100 000) than in northern provinces (142.63/100 000), and the annual reported incidence rate of intestinal infectious diseases was higher in coastal provinces (279.52/100 000) than in inland provinces (181.78/100 000), the differences were all significant (both P<0.001). Conclusions:During 2013-2022, the incidence of intestinal infectious diseases decreased significantly in China, with HFMD and other infectious diarrhea as the main diseases. Strengthened surveillance for intestinal infectious diseases should be carried out in key groups, such as children living scatteredly and farmers, and targeted prevention and control measures should be taken according to the epidemiological characteristics of different diseases to effectively reduce the incidence of intestinal infectious diseases.
9.Clinical efficacy and safety of a domestic calcipotriol/betamethasone dipropionate ointment in the treatment of stable plaque psoriasis: a multicenter, randomized, double-blind, controlled study
Lixin XIA ; Guang XIANG ; Qingchun DIAO ; Kun HUANG ; Shoumin ZHANG ; Shanshan LI ; Yumei LI ; Zhiqiang SONG ; Qing SUN ; Xiumin YANG ; Meng PAN ; Yuling SHI ; Shuping GUO ; Huiping WANG ; Tiechi LEI ; Xiaoyong ZHOU ; Songmei GENG ; Suchun HOU ; Juan SU ; Yong CUI ; Rixin CHEN ; Yanyan FENG ; Hongxia FENG ; Rushan XIA ; Zudong MENG ; Fang YIN ; Jingjing WANG ; Xinghua GAO
Chinese Journal of Dermatology 2025;58(11):1020-1026
Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.
10.Epidemic characteristics and trend analysis of acute hemorrhagic conjunctivitis in China from 2015 to 2022
Yunfei ZHANG ; Yue SHI ; Jianfeng JIANG ; Xuedong ZHENG ; Baijun JIN ; Zhaorui CHANG ; Tian QIN ; Mengjie GENG ; Shiwen WANG
Chinese Journal of Experimental and Clinical Virology 2025;39(3):270-277
Objective:To analyze the epidemiological characteristics and trend of acute hemorrhagic conjunctivitis (AHC) in China from 2015 to 2022, and to provide evidence for the adjustment of prevention and control strategies and measures for AHC.Methods:The case data of AHC reported by national notifiable disease information system from 2015 to 2022 were collected, and descriptive analysis method were used to analyze the population distribution characteristics, temporal epidemiological trends and spatial clusters of AHC in China.Results:From 2015 to 2022, the incidence of AHC in China ranged from 1.85/100 000 to 2.97/100 000, with a fluctuating downward trend. The average annual percent change (AAPC) was -4.91 (95% CI: -7.74 to -2.00, P<0.05), with an annual percent change (APC) of 2.73 (95% CI: -2.34 to 8.06, P=0.189) for 2015—2019 and an APC of -14.23 (95% CI: -21.78 to -5.94, P<0.05). The age-specific incidence rate was highest in children aged 0-4 years (fluctuating between 4.69 and 5.67/100 000 from 2015 to 2019; It decreased significantly during 2020—2022, fluctuating between 1.93 and 2.72 per 100 000).The proportion of cases in children at 0-4 years of age showed a fluctuating downward trend from 8.68% in 2015 to 3.76% in 2020, with an increase in 2021—2022 to 5.74%. After 2020, the proportion of the population aged 60 years and above has increased, reaching 33.59% in 2022. Cases were mainly farmers, with a fluctuating upward trend of around 50% per year, with the highest percentage of 60.96% in 2020. The peak seasonal incidence of AHC was obvious from May to September from 2015 to 2019, but it was not obvious in 2020—2022. The cases were mainly distributed in Guangxi, Hainan and other provinces in the southwestern part of China. The high incidence counties were concentrated in Leye County of Guangxi, Maojian District of Hubei, Fuchuan Yao Autonomous County of Guangxi, Funing County of Yunnan, and Pulan County of Tibet every year. Conclusions:The overall epidemic rate of AHC in China showed a fluctuating downward trend from 2015 to 2022, with a pronounced decline observed between 2020 and 2022, potentially linked to non-pharmaceutical interventions during the COVID-19 pandemic. Increased attention needs to be given to farmers and people above 60 years of age to reduce the risk of morbidity. Moreover, prevention and control efforts should be strengthened in high-risk areas of southwestern China, and comprehensive measures should be implemented in counties with high incidence, including enhanced health education campaigns and improved allocation of sanitary facilities, to reduce the risk of AHC infection. This study is the first to highlight the potential impact of public health policies on AHC epidemiology, thereby offering a scientific foundation for population- and region-specific precision prevention strategies, particularly guiding the refinement of control measures in high-burden areas.

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