Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

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.

Objective To investigate the prevalence and risk factors of cognitive impairment in the nursing home population in Changning District, Shanghai. Methods In this study, random cluster sampling method was used to select 570 elderly people from 5 nursing homes in Changning District. Multivariate logistic regression was used to analyze the risk factors influencing cognitive function. Results The total prevalence of cognitive impairment in Changning nursing home population was 22.5%. The prevalence rates of ≤80 and >80 age groups were 16.8% and 23.9%, respectively, and the prevalence rates of men and women were 19.2% and 23.9%, respectively. Multivariate analysis showed that age ≥ 80 years old (OR=1.839, 95% CI: 1.045~3.235), no habit of reading book or newspaper (OR=2.087, 95%CI: 1.282~3.398), limitation of daily activity ability (OR=1.577, 95% CI: 1.023~2.431), and having depressive symptoms (OR=2.809, 95% CI: 1.840~4.288) were all influencing factors for cognitive impairment. Conclusion More than one fifth of elderly people in nursing homes in Changning District have symptoms of cognitive impairment. It is necessary to carry out routine cognitive assessment and appropriate cognitive intervention for the nursing home population to reduce the health and economic losses caused by cognitive impairment.

Purpose To investigate the diagnostic value of 18F-FDOPA PET/CT imaging and semi-quantitative analysis platform for the diagnosis of Parkinson's disease(PD).Materials and Methods There were 27 healthy controls and 56 clinically diagnosed PD patients,including 33 early PD(Hoehn-Yahr class Ⅰ-Ⅱ)and 23 advanced PD(Hoehn-Yahr class Ⅲ-Ⅳ),underwent 18F-FDOPA PET imaging in Nanjing First Hospital,Nanjing Medical University were consecutively enrolled from January 2018 to December 2019.The striatal to occipital ratio(SORs)in radioactivity was calculated by HERMES BRASS platform,thereby completing the semi-quantitative analysis of the brain based on regions of interest and observing the asymmetry of the striatal subregions in early-stage PD and late-stage PD patients.Using artificial intelligence techniques to perform principal component analysis on the SORs of the striatal subregions in PD group and healthy control group,the degree of data aggregation and the distinguishability between groups were observed.Results The SORs was significantly reduced in the whole caudate,anterior,posterior putamen and striatum of advanced PD patients(t=9.02-11.72,P<0.000 1).The area under the curve was 0.952,0.973,0.995 and 0.982,respectively.Compared with the healthy control group,the loss of striatal asymmetry index(mean)in each subregion of the striatum in early PD group was caudate(7.61±5.50)%,anterior putamen(11.43±8.97)%,posterior putamen(17.17±11.63)%,and whole striatum(10.65±7.46)%,respectively.The uptake of 18F-FDOPA in the striatum of PD patients was significantly reduced,and the most obvious loss of early PD patients was contralateral posterior putamen,with a decrease of 34%.Conclusion The platform semi-quantitative analysis of 18F-FDOPA PET/CT images provides objective semi-quantitative values for early diagnosis and differential diagnosis of PD.Asymmetry in the striatum,especially in the putamen,may be an important parameter for early diagnosis of PD..

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion.Methods:Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma).Results:Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion.Conclusion:By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

Objective To explore the mechanism of Buyang Huanwu Decoction for"treating different diseases with same therapies"in type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)based on network pharmacology and molecular docking techniques.Methods Firstly,the active ingredients of seven herbs in Buyang Huanwu Decoction were searched and screened by TCMSP,SymMap and other databases,the target prediction of these active ingredients was carried out by PharmMapper.The disease targets of T2DM and AD were collected from OMIM,DrugBank,GeneCards and Disgenet databases.The potential targets of Buyang Huanwu Decoction for"treating different diseases with same therapies"in T2DM and AD were obtained by intersecting with targets of active ingredients and the disease targets.Then STRING database and Cytoscape software were used to construct the PPI network and"herbs-components-targets"network,respectively.The core targets and pharmacodynamic components were screened through network topology analysis.Furthermore,GO functional and KEGG enrichment analysis was performed for potential targets using Metascape database.Finally,AutoDock software was used to verify the molecular docking between the selected components and targets.Results Ninety-four active components of Buyang Huanwu Decoction can act on 342 protein targets,and 100 intersection targets were obtained by comparing with 3 140 AD targets and 1 708 T2DM targets.GO functional enrichment analysis showed that these targets were mainly involved in MAPK cascade-mediated regulation,hormone-mediated signaling pathways,cellular response to lipids,regulation of inflammation response and other biological processes.MAPK,PI3K/Akt,FoxO,AGE/RAGE,insulin resistance,lipid and atherosclerosis,and non-alcoholic fatty liver signaling pathway were significantly enriched in KEGG analysis.PPI and topology analysis of"herbs-components-targets"network were used to screen out 10 core targets such as MAPK8,MAPK14,GSK3B,PPARG,and 10 core pharmacodynamic components such as paeoniflorin,benzoyl paeoniflorin,(+)-catechin.The results of molecular docking showed that these components had strong binding ability to the targets.Conclusion The core components of Buyang Huanwu Decoction,such as paeoniflorin and catechin,may act on PPARG,GSK3B and other key targets,and participate in the regulation of signaling pathways including MAPK and PI3K/Akt,which play a role in"treating different diseases with the same therapies"of T2DM and AD.

Objective:To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease.Methods:From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease.Results:In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR) value of 0.81 (95% CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions:In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Objective To investigate the current situation of home environment safety of the elderly in Changning District, identify the risk factors related to the fall of the home environment of the elderly, and take targeted rectification measures, so as to create a safer environment for the elderly. Methods A phased random sampling method was used to select 201 elderly households from 10 streets in Changning District. Community doctors conducted on-the-spot investigation and assessment to collect information, and Epidata3.1 was used to input data and SAS 9.2 was used for statistical analysis. Results The incidence of falls in the past year was 19.90%, and the score of environmental risk factors/the number of environmental risk factors in each family ranged from 0 to 25, with an average of 9 items (standard deviation of 4.71). The results of multivariate logistic regression analysis show that the high level of falling environment (the number of falling risk factors in home environment ≥12) is still an independent risk factor for falls of the elderly, except for the influence of age and the number of drugs taken (OR=3.835, 95% CI:1.718-8.561). Conclusion The environmental risk factors causing falls are common in the home environment of the elderly in the community. It is necessary to focus on improving the home environment, reducing the risk of falls for the elderly, and creating a safe and comfortable home environment for the elderly.