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.

Tujia ethnic group medicine Xuetong is derived from Kadsura heteroclita, the stem of which has the medicinal value for anti-rheumatoid arthritis, liver protection, anti-tumor, anti-oxidation effects, and has been widely used in Hunan and Guangdong in China. The selection of reliable and stable reference genes is the basis for subsequent molecular research on K. heteroclita. In this study, GAPDH, TUA, Actin, UBQ, EF-1α, 18S-rRNA, CYP, UBC, TUB, H2A, and RPL were selected as candidate reference genes in Kadsura heteroclita. The gene expression levels of the 11 candidate reference genes of K. heteroclita in its 6 different parts(stem-inside of the cambium, stem-outside of the cambium, fruit, flower, root, and leaf) and under different intervention conditions [drought stress, salt stress, and methyl jasmonate(MeJA) treatment] were detected by quantitative real-time polymerase chain reaction(qRT-PCR). The expression stability of the 11 candidate reference genes was comprehensively analyzed and evaluated by geNorm, NormFinder, ΔCT algorithm, and RefFinder software. The results showed that the expression of UBC and RPL was relatively stable in 6 different parts, and UBC and GAPDH genes were relatively stable under different intervention conditions. To verify the reliability of reference genes for K. heteroclita, this study further examined the relative expression levels of KhFPS, KhIDI, KhCAS, KhSQE, KhSQS, KhSQS-2, KhHMGS, KhHMGR, KhMVD, KhMVK, KhDXR, KhDXS, KhPMVK, and KhGGPS in different parts and under different intervention conditions, which might relate to the synthesis of the main component(Xuetongsu) of K. heteroclita. The results showed that with UBC and RPL or UBC and GAPDH as the reference genes, the expression trends of these 14 genes were basically consistent in different parts or under different intervention conditions for K. heteroclita. In conclusion, UBC can be used as a reference gene of K. heteroclita for its different parts and different intervention conditions, which lays a foundation for further research on the biosynthetic pathway of main components in K. heteroclita.
Real-Time Polymerase Chain Reaction/methods* ; Reference Standards ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; Plant Proteins/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Based on the theory of 'bi （痹） of both body and viscera'， this paper systematically discussed the pathogenic evolution of rheumatoid arthritis （RA） complicated by sarcopenia from the perspective of traditional Chinese medicine （TCM）. It is proposed that a transformation pathway is muscle bi to spleen bi and then atrophy bi， and the core pathogenesis is diaharmony of ying （营） and wei （卫）. Combining modern molecular biology research， it is suggested that imbalances in skeletal muscle homeostasis mediated by the tumor necrosis factor-like weak inducer of apoptosis-ibroblast growth factor-inducible 14 （TWEAK-Fn14） axis may provide the material basis for the evolution of this disease. Furthermore， this authors proposed TCM treatment strategies， including "regulating and tonifying ying and wei， warming yang and moving bi， nourishing the viscera by supporting the body"， and "promoting the spleen and resolving turbidity， clearing heat and promoting circulation， regulating the organs and calming the body". These strategies emphasize the simultaneous treatment of body and viscera， integrated prevention and treatment， so as to provide TCM theoretical foundation and clinical approaches for preventing and treating RA complicated by sarcopenia.

BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P＜0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P＜0.05,P＜0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.

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.

ObjectiveTo establish an allele-specific polymerase chain reaction （PCR） method for identifying Scolopendra dispensing granules， so as to ensure the quality and therapeutic effects of Scolopendra and its preparations. MethodThe primer interval suitable for the PCR was selected based on the cytochrome c oxidase subunit 3（COX-3） gene sequence of Scolopendra， and the single nucleotide polymorphism （SNP） loci of Scolopendra and its adulterants were mined from the interval for the design of specific primers. The samples of Scolopendra and its adulterants were collected. The PCR system was established and optimized regarding the annealing temperature， cycles， Taq enzymes， DNA template amount， PCR instruments， and primer concentrations， and the specificity and applicability of this method were evaluated. ResultThe PCR system was composed of 12.5 μL 2×M5 PCR Mix， 0.4 μL forward primer （10 μmol·L^-1）， 0.4 μL reverse primer （10 μmol·L^-1）， 2.5 μL DNA template， and 9.2 μL sterile double distilled water. PCR parameters： Pre-denaturation at 94 ℃ for 3 min， 30 cycles （94 ℃ for 20 s， 62 ℃ for 20 s， 72 ℃ for 45 s）， and extension at 72 ℃ for 5 min. After PCR amplification with the system and parameters above， the electrophoresis revealed a bright band at about 135 bp for Scolopendra and no band for the adulterants. ConclusionThe established allele-specific PCR method can accurately identify the medicinal materials， decoction pieces， and standard decoction freeze-dried powder of Scolopendra， as well as the intermediates and final products of Scolopendra dispensing granules， which is of great significance for ensuring the quality and clinical efficacy of Scolopendra and its preparations.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

Objective:To investigate the risk factors and cumulative risk of myopia in children and adolescents, providing a basis for identifying cumulative risk factors in preventing and controlling myopia.Methods:Baseline data from the mental and physical health cohort of children and adolescents established in Inner Mongolia Autonomous Region were used. A stratified random cluster sampling method was adopted to select 138 974 students from fourth to twelfth grade as participants. Distance visual exams, refractive assessments, and questionnaires were conducted on the included students. Logistic regression analysis was used to evaluate each risk factor's impact on myopia's prevalence. The number of risk factors was summed to form a cumulative risk score, and logistic regression analysis was conducted to examine the association between the cumulative risk score and the prevalence of myopia. Additionally, the association between the cumulative risk score of myopic students and their degree of refractivity was analyzed using a generalized estimating equation.Results:The study found a high prevalence of myopia among children and adolescents at baseline (70.2%). Girls exhibited a higher prevalence (74.8%) than boys (65.6%), urban areas (74.3%) surpassed suburban ones (68.6%), and the incidence was greater in high schools (80.3%) compared to middle schools (75.3%), which, in turn, was higher than in elementary schools (57.7%) (all P<0.05). Analysis of risk factors revealed that children and adolescents experiencing improper reading and writing distances ( OR=1.10, 95% CI: 1.07-1.13), excessive homework ( OR=1.09, 95% CI: 1.06-1.12), insufficient sleep ( OR=1.10, 95% CI: 1.07-1.13), having myopic father ( OR=1.98, 95% CI: 1.91-2.05), having myopic mother ( OR=2.04, 95% CI: 1.97-2.10), or using classroom chairs not matched to their height faced ( OR=1.04, 95% CI: 1.01-1.07) increased myopia risks. Additionally, the prevalence and significant odds ratio of myopia increased with the increase in cumulative risk score, with every additional unit of cumulative risk score increasing the right eye's refractive error by -0.10 D. Conclusion:The presence of multiple factors and their comprehensive score increases the prevalence of myopia in children and adolescents.