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.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets （TWP） in the treatment of rheumatoid arthritis （RA） in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database （CERTAIN） from January 1，2019 to January， 2024 were collected. According to the inclusion and exclusion criteria， data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching （PSM） was used in both groups to keep the baseline balanced and comparable. The disease activity score （DAS28-ESR） of 28 joints based on the erythrocyte sedimentation rate （ESR）before and after treatment was compared between the two groups， as well as health assessment questionnaire （HAQ），visual analogue scale （VAS），tender joint count （TJC），swollen joint count （SJC）， patient's global assessment （PGA），evaluator's global assessment （EGA），laboratory indexes， clinical curative effect， and adverse reactions. ResultA total of 3 978 patients were included，including 929 in the exposure group and 3 049 in the control group. Before PSM，there were significant differences in demographic information，DAS28-ESR score，PGA，EGA，HAQ，VAS scores，SJC， and TJC between the two groups （P<0.05）. After successful PSM matching，922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment，and the differences in other indexes between the two groups decreased to varying degrees. After treatment，the DAS28-ESR，PGA，EGA，HAQ，SJC，TJC，VAS scores， ESR，and IgG immune index of the two groups were significantly lower （P<0.01）. Compared with those in the control group after treatment，the DAS28-ESR，PGA，EGA，HAQ，VAS scores， and ESR in the exposure group after treatment decreased more significantly （P<0.05，P<0.01）. There was no significant difference in TJC in the exposure group after treatment. However， TJC in the exposure group was significantly higher than that in the control group before treatment （P<0.05）. In terms of TJC reduction，the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment，the clinical symptoms of poor appetite，insomnia and many dreams，upset，fatigue，and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group （P<0.01），there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR，PGA，EGA，HAQ，TJC，and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable，it shows good security.

Progressive fibrosing interstitial lung disease （PF-ILD） has a complex etiology， and is classified as lung impediment stage， impediment-atrophy combination stage， and lung atrophy stage according to the different clinical manifestations during the progression of disease. Based on the theory of opening-closing-pivoting to analyse the characteristics of yin and yang disease mechanism and the idea of prescriptions in the three stages. For lung impediment stage， main as three-Yang fail to keep inside， disharmony between Ying qi （营气） and Wei qi （卫气）， shaoyin impairment， treatment should use Mahuang （Ephedra sinica） and Guizhi （Neolitsea cassia） flexibly to form a formula， or choose pungent-dispersing formulas like Baidu Powder （败毒散） to move qi and save yang， and diffuse and disperse impediment pathogen， meanwhile combining saving-shaoyin medicinals like Fuzi （Aconitum carmichaelii） and Shudihuang （Radix Rehmanniae Praeparata） to reinforce healthy qi and dispel pathogen； for impediment-atrophy combination stage， rooted as yangming impairment and progressed by over-movement of qi， treatment should use Mahuang Shengma Decoction （麻黄升麻汤） to resolve and decrease over-activities， emphasis on both opening and closing， and improve impediment and atrophy； for lung atrophy stage with three-Yin in a bad condition simultaneously and poor prognosis， treatment should use modified Jinshui Liujun Decoction （金水六君煎） to consolidate qi and save yin， disperse phlegm and stasis， to improve the quality of life for patients with PF-ILD.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.