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.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

Tick-borne encephalitis is a central nervous system disease caused by infections with tick-borne pathogens, which is characterized by severe clinical symptoms, multiple sequelae, and a high fatality rate. Currently, there is no cure for tick-borne encephalitis. Tick-borne encephalitis virus (TBEV) is the most common pathogen of tick-borne encephalitis. Therefore, rapid and accurate detection of TBEV contributes to reducing the mortality of tick-borne encephalitis, improving patients' prognosis, and reducing the risk of TBEV transmission. The currently available serological tests for detection of TBEV infections mainly include neutralization test, enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay, and nucleic acid tests mainly include polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), reverse transcription polymerase spiral reaction, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas)-based assays. This review summarizes the progress of researches on serological and nucleic acid tests for detection of TBEV infections, so as to provide insights into prevention and control of tick-borne encephalitis.

Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

Objective To investigate the protective mechanism of oxidative stress injury of SD rats NR8383 by budesonide.Methods Rat alveolar macrophages NR8383 were divided into 5 groups:blank group was given serum-free K12 medium without any treatment;lipopolysaccharide(LPS)group was given 2.29 μg·mL-1 LPS standard solution;budesonide group(budesonide),c-Jun inhibitor group(AS601245)and budesonide+c-Jun inhibitor group(budesonide+AS601245)were given budesonide 28.0 μL,c-Jun inhibitor AS601245 2.50 μg,and budesonide 28.0 μL+c-Jun inhibitor AS601245 2.50 μg based on the LPS group,respectively.Cells in 5 groups were incubated in serum-free K12 medium at constant temperature for 24 h.The apoptosis rate at 24 h was examined by cell counting kit-8(CCK-8)assay;c-Jun mRNA expression was detected by real-time quantitative polymerase chain reaction(q-PCR);oxidative stress damage factor reactive oxygen species(ROS),8-hydroxy-2-deoxyguanosine(8-OHdG),glutathione peroxidase(GSH-Px),thioredoxin reductase-1(TRX-1)expression were detected by enzyme-linked immunosorbent assay(ELISA);c-Jun signaling pathway protein expression in each group by Western blot.Results Compared with LPS group(29.88±5.98)％,24 h apoptosis rate was significantly decreased in budesonide group,c-Jun inhibitor group,budesonide+c-Jun inhibitor group and blank group[(20.15±6.66)％,(15.39±3.54)％,(12.11±2.55)％and(8.52±1.27)％,respectively],the differences were statistically significant(all P＜0.05).The ROS in budesonide group,c-Jun inhibitor group,budesonide+c-Jun inhibitor group,LPS group and blank group were(3.16±0.19),(4.15±0.33),(2.21±0.21),(6.52±0.36)and(1.06±0.23)U·g-1;8-OHdG were(10.55±1.23),(11.14±1.06),(9.55±1.00),(15.66±1.99)and(8.27±1.13)ng·mL-1;GSH-PX were(188.52±12.33),(200.52±27.97),(144.52±20.55),(335.14±30.10)and(126.55±12.52)U·mL-1;TRX-1 were(40.11±6.66),(50.55±10.07),(60.25±10.55),(115.36±20.03)and(16.55±2.33)ng·mL-1;the relative c-Jun mRNA expressions were 0.56±0.03,0.44±0.11,0.25±0.04,0.89±0.12 and 0.08±0.01;c-Jun/GAPDH protein relative expression were 3.15±0.22,2.36±0.14,1.55±0.13,4.02±0.22 and 0.88±0.12.Compared with the LPS group,the differences of indicators in the budesonide group,c-Jun inhibitor group and budesonide+c-Jun inhibitor group possessed statistical significance(all P＜0.05).Conclusion Budesonide significantly increased the survival rate of NR8383 cells and significantly decreased the concentrations of oxidative damage representative factors ROS,GSH-Px,8-OHdG and TRX-1,its oxidative damage protection mechanism may be related to the regulation of c-Jun protein.

Tezepelumab(AMG 157/MEDI9929)is a human monoclonal antibody against the epithelial cell-derived cytokine thymic stromal lymphopoietin(TSLP).It is primarily used to treat moderate to severe asthma,particularly in patients with a non-eosinophilic inflammatory phenotype,whose asthma remains uncontrolled despite the use of long-acting beta-agonists and moderate to high doses of inhaled glucocorticoids.This article will summarise the mechanism of action,clinical trial efficacy and safety and tolerability of Tezepelumab in order to provide a comprehensive understanding of the drug and inform clinical work.

Type 2 diabetes mellitus(T2DM)and its chronic complications are the main causes of disability and death in diabetic patients.Traditional Chinese medicine has the advantages of significant curative effect and low recurrence rate.In recent years,the basic research on the treatment of T2DM with traditional Chinese medicine has made significant progress,and its mechanism may be related to the regulation of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signal pathway by traditional Chinese medicine.This paper expounds the relationship between JAK/STAT signaling pathway and T2DM,and summarizes the research progress of traditional Chinese medicine extract and compound prescription in the intervention of T2DM by regulating this signaling pathway,in order to provide references for the clinical application of T2DM therapeutics and the development of new drugs.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.