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 evaluate the effectiveness of amplification intervention with hearing aids for restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss. Methods:This study selected 30 patients with normal hearing in one ear and moderate to severe sensorineural hearing loss in the other ear. They were fitted with hearing aids for the worse ear and underwent more than half a year and one year of adaptation training. The Chinese translation of the Twelve-item version of SSQ（C-SSQ12）, angle identification test, speech recognition score（SRS） at different signal-to-noise ratios（SNR=5 and SNR=10） and audiometric thresholds were used to compare the results before and after hearing aid use to evaluate the effectiveness of the unilateral hearing loss intervention. Results:The results of the audiometric thresholds, C-SSQ12 scores, angle identification test, and SRS at SNR=5 and SNR=10 in the worse ear of the unilateral hearing loss patients after hearing aid use were all statistically significant compared to before hearing aid use（P<0.01）. Conclusion:Amplification intervention with hearing aids has significant effects on restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss.
Humans ; Hearing Aids ; Hearing Loss, Unilateral/therapy* ; Middle Aged ; Hearing Loss, Sensorineural/rehabilitation* ; Adult ; Female ; Male ; Auditory Threshold ; Young Adult ; Aged

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Objective:To analyze and compare the pathological data characteristics of patients with simple papillary thyroid carcinoma (PTC) and PTC combined with Hashimoto’s thyroiditis (HT), so as to provide clinical treatment ideas.Methods:A retrospective analysis was performed on the medical records of 326 PTC patients who met the requirements and underwent surgical treatment in the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine from Jan. 2020 to May. 2022. There were 81 males and 245 females. They were divided into PTC group and HT-PTC group, according to whether they were combined with HT. Clinical data were collected and organized. The collection indicators included patient gender, age, body mass index (BMI), five preoperative thyroid function items including free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), BRAF gene mutation, single or bilateral lesions, single or multiple lesions, largest postoperative pathological tumor lesions diameter, cervical lymph node metastasis (LNM) status, etc. At the same time, all patients were divided into CLNM group and no CLNM group according to CLNM status. The two groups were compared in terms of gender, age ≥55 years old, whether combined with HT, number of lesions, unilateral and bilateral, extraglandular invasion, microcarcinoma, and BRAF gene. Statistical software was used to analyze the results. t test, χ2 test, and logistic regression analysis were adopted. P<0.05 indicates that the difference is statistically significant. Results:The proportion of female patients in both groups was higher, and the proportion of female patients in the HT-PTC group (90/100, 90%) was higher than that in the PTC group (155/226, 69.59%). HT-PTC patients were younger than patients in the PTC group (43.03±12.72 vs. 43.70±12.63) years old, and their TSH (2.71±1.69 vs. 2.02±1.46) uIU/mL was higher. The differences were statistically significant (all P<0.05). There were no statistically significant differences in BMI, FT3, FT4, T3, or T4 (all P>0.05). The HT-PTC group had a lower proportion of BRAF gene mutations [87/100 (87%) vs. 212/226 (93.8%) ], a smaller maximum tumor diameter (1.06±0.73 vs. 1.32±0.97 cm), and a lower proportion of CLNM [37 /100 (37%) vs. 118/226 (52.2%) ]. The number of LNMs with metastasis is less (3.33±2.21 vs. 4.76±4.00), and it was more likely to be multifocal [44/100 (44%) vs. 73/226 (32.74%) ]. All differences were statistically significant (all P<0.05), and the differences in bilateral gland lobes involvement and extra-glandular invasion were not statistically significant. When accompanied by CLNM, gender (male vs. female) [55/100 (35.45%/64.52%) vs. 26/145 (15.2%/84.85%) ], age ≥ 55 years (yes vs. no) [21/134 (13.55) %/86.45%) vs. 50/121 (29.24%/70.76%) ], HT (yes vs. no) [37/118 (23.87%/76.13%) vs. 63/108 (36.84%/63.16%), number of lesions (single focus vs. multiple focus) [90/65 (41.94%/50.06%) vs. 119/52 (69.59%/30.41%) ], microcarcinoma (yes vs. no) [83/72 (53.55%/45.45%) vs. 139/32 (81.29%/18.71%) ] and extraglandular invasion (with vs. without) [38/117 (24.52%/75.48%) vs. 27/144 (17.42%/84.21%) ] had statistics significance (both P<0.05). There was no statistical significance in bilateral lesion involvement or BRAF gene mutation (all P>0.05). Multivariate logistic regression analysis showed that age, microcarcinoma, HT, gender, and number of lesions were independent risk factors for CLNM, and male gender and multifocal cancer were risk factors for CLNM. Age ≥55 years, microcarcinoma, and combined HT were negatively associated with CLNM. Conclusions:HT may promote the occurrence of PTC, but can inhibit its development. In the short term, patients with HT can have a better prognosis than those with simple PTC.

BACKGROUND:Irisin,a myokine isolated from the transmembrane protein FNDC5 by muscle cells during exercise,has the function of inducing the browning of white adipose tissue,but its effect on lipotoxicity-induced osteogenic differentiation and the mechanism is unclear. OBJECTIVE:To investigate the effect of irisin on the osteogenic ability of palmitic acid-induced bone marrow mesenchymal stem cells and the mechanism of action. METHODS:CCK-8 assay was used to detect the effect of different concentrations of palmitic acid on the proliferation of mouse bone marrow mesenchymal stem cells and the effect of irisin on the proliferation of mouse bone marrow mesenchymal stem cells in the presence of palmitic acid.After pretreatment with irisin and palmitic acid for 24 hours,osteogenic differentiation of mouse bone marrow mesenchymal stem cells was induced by alkaline phosphatase staining as well as qRT-PCR was performed to detect the expression of osteogenesis-related genes on day 7 of osteogenic induction culture.The expression of proteins related to the AMPK/BMP2/SMAD signaling pathway was detected by western blot assay.Alizarin red staining was conducted on day 21 to detect osteogenic differences. RESULTS AND CONCLUSION:(1)The CCK-8 assay results suggested that the amplification of bone marrow mesenchymal stem cells was inversely proportional to the concentration of palmitic acid,but at 0.02 mmol/L concentration,palmitic acid had no significant effect on the amplification of bone marrow mesenchymal stem cells,and irisin did not affect the proliferation of bone marrow mesenchymal stem cells when its mass concentration was in the range of 0.1-20 μg/L.(2)Alkaline phosphatase staining and alizarin red staining showed that palmitic acid inhibited the osteogenic differentiation ability of bone marrow mesenchymal stem cells.Irisin improved palmitic acid-induced osteogenic inhibition of bone marrow mesenchymal stem cells.qRT-PCR results showed that palmitic acid could cause the downregulation of osteogenic-related genes,and irisin could inhibit this trend.(3)Western blot assay results showed that compared with the palmitic acid intervention group,irisin treatment enhanced AMPK/BMP2/SMAD signal transduction in bone marrow mesenchymal stem cells.It is found that irisin can improve the osteogenic differentiation ability of bone marrow mesenchymal stem cells pretreated with palmitic acid,and proposed that the specific mechanism might be mediated by AMPK/BMP/SMAD signaling pathway.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

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.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.