BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Inflammation is the body’s response to damage， infection or other stimuli， but its excessive or continuous development can lead to a variety of diseases. Although modern medical anti-inflammatory therapies were widely used， it is often accompanied by limitations such as more adverse reactions. Based on the “holistic view” and “differential treatment”， traditional Chinese medicine （TCM） regards inflammation as a manifestation of the imbalance of yin and yang in the body and the conflict between good and evil. The application of anti-inflammatory TCM is not only aimed at the pathological state of “inflammation”， but also based on the overall consideration of “syndrome”. According to different types of syndrome， anti-inflammatory TCM can be divided into heat-clearing and detoxifying agents （such as Lonicera japonica and Isatis indigotica ）， heat-clearing and drying dampness agents （such as Coptidis Rhizoma）， blood-activating and stasis-dissolving agents （such as Salvia miltiorrhiza ） and vital qi-strengthening and pathogenic factor-expelling agents （such as Panax ginseng ）. Four types of anti-inflammatory TCM restore the body’s immune balance through the systematic regulation of multi-component， multi-target and multi-pathway， exhibiting a good anti-inflammatory effect. Future research should focus on integrating systematic biology， applying artificial intelligence， carrying out high-quality evidence-based research， and combining traditional Chinese medicine and Western medicine， so as to reveal the overall regulatory law of anti-inf lammatory effects of TCM and promote clinical rational use.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Objective: To systematically evaluate the clinical efficacy of topical preparations of Mongolian medicine Manggari hot compress therapy (hereafter referred to as Manggari hot compress therapy) in treating cervical spondylotic radiculopathy (CSR) and explore the possible pharmacological material basis in the formula, providing evidence for the clinical application of Mongolian medicine in the treatment of CSR. Methods: The clinical trial employed a randomized, controlled, open-label, and outcome-assessor-blinded design. The CSR patients who were treated at the Department of Traditional Therapeutics Outpatient Clinic, Xilinguole Meng Mongolian General Hospital between July 1, 2024 and August 31, 2025, were enrolled. They were randomly assigned to three groups: an oral control group (administration of oral administration of mecobalamin tablets combined with cervical electric traction), an experimental group (Manggari external hot compress), and a patch control group (flurbiprofen gel plaster). The intervention lasted two weeks. Before and after treatment, the following subjective indicators were recorded: Mongolian Medicine Syndrome (MMS) score, Visual Analog Scale (VAS) score, Northwick Park Neck Pain Questionnaire (NPQ) score, and tongue morphology. Serum levels of inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β)] and oxidative stress markers [malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity] were measured using enzyme-linked immunosorbent assay (ELISA). Overall therapeutic efficacy was evaluated. One month after treatment completion, a follow-up assessment was conducted, and the MMS, VAS, and NPQ scores were recorded again for all patients. For the pharmacological substance exploration, ultra-high-performance liquid chromatography-Q-exactive orbitrap-mass (UHPLC-QE-MS) was employed to analyze blood-absorbed prototype components of Manggari, under both positive and negative ion modes. The targeting relationship between the core active compounds and the target protein was validated using molecular docking. Results: This study ultimately included 90 patients with CSR for analysis. Baseline characteristics showed no statistically significant differences among the three groups (P > 0.05). (i) Symptom scores. After treatment, the MMS, VAS, and NPQ scores decreased significantly from baseline in all three groups (P < 0.001). At follow-up, there was no significant difference in MMS, VAS, and NPQ scores of the experimental group compared with those at the end of the treatment (P > 0.05). After treatment, the experimental group showed significantly greater reductions in MMS, VAS, and NPQ scores than oral control and patch control groups (P < 0.001). At follow-up, these differences remained significant (P < 0.001). (ii) Inflammatory and oxidative stress markers. After treatment, serum levels of TNF-α, IL-6, and IL-1β, and MDA activity decreased significantly from baseline in all three groups (P < 0.001), and SOD content and GSH-Px activity increased significantly from baseline (P < 0.05). After treatment, the experimental group had significantly lower serum levels of TNF-α, IL-6, and IL-1β than oral and patch control groups. Additionally, it exhibited lower MDA activity and higher SOD content and GSH-Px activity compared with the two control groups. (P < 0.05). (iii) Overall efficacy. The total effective rate was 93.33% in the experimental group, 86.66% in the oral control group, and 83.33% in the patch control group. (iv) Pharmacological substance analysis. A total of 152 compounds were identified in the blood-absorbed components of Manggari. Among them, the core compounds—4-hydroxycoumarin, N-methylanthranilic acid, genistein, and ginsenoside-Rk1—showed binding energies to the key target proteins TNF-α and IL-1β range from − 4.7 to − 7.1 kcal/mol, with the majority of the binding energies being below − 5.0 kcal/mol, suggesting that it generally has a good binding affinity. Conclusion Mongolian medicine hot compress therapy effectively modulates inflammatory and oxidative stress responses through the combined action of its thermal effects and active pharmaceutical ingredients Manggari. It inhibits cervical nerve root inflammation and alleviates radicular pain, improving clinical symptoms, reducing pain severity, and alleviating neck functional disability.

Objective To understand the epidemiological characteristics of a clustered outbreak of severe fever with thrombocytopenia syndrome(SFTS)as well as the ecological tick monitoring results for Zibo City, and to provide a scientific basis for formulating prevention and control strategies. Methods A case definition was cited before epidemic investigations were performed. Epidemiological investigations were performed on the index cases and their close contacts. Blood samples were collected from cases and close contacts, and quantitative real-time RT-PCR was used to detect SFTS virus(SFTSV)nucleic acid sequences. A retrospective cohort study was conducted to analyze risk factors and develop prevention and control strategies. Results This clustered outbreak involved two index cases and six close contacts with no deaths. Case A exhibited symptom onset on July 26. SFTS was confirmed on August 2. Case B exhibited symptom onset on August 1, and SFTS was confirmed on August 3. Patient B reported a recent history of tick bites. In both index cases, the incubation period for SFTS was inferred to be 7-12 days. The time interval from symptom onset to clinical diagnosis in the two cases ranged from 2-8 days, with an average period of 5 days. SFTSV nucleic acid test result were positive for both patients, whereas all six close contacts tested negative. All captured ticks tested negative for SFTSV using quantitative real-time RT-PCR. The densities of parasitic and free-living ticks in the emergency monitoring area around the cases were 12.60 and 4.65 ticks/(flag·100 m). In 2024, the average parasitic tick index and free-living tick density index were 4.21 and 2.43 ticks/(flag ·100 m)in Yiyuan County, respectively. Conclusions No evidence of human-to-human transmission was found in the assessed SFTS clusters. The infections were likely acquired through tick bites during fieldwork, and the risk of a subsequent outbreak spreading was low.

Electroencephalography (EEG) is a non-invasive neurophysiological monitoring technique. It records the electrical activity of the cerebral cortex using electrodes placed on the scalp surface. Owing to its high safety, portability, and millisecond-level temporal resolution, EEG has been widely utilized in a variety of fields, including clinical diagnosis, brain-computer interfaces (BCIs), and cognitive neuroscience research. However, due to its microvolt-level amplitude, EEG is highly susceptible to various artifacts, including electrooculographic (EOG), electrocardiographic (ECG), electromyographic (EMG), and power line interference (PLI). These artifacts can obscure genuine neural activity and introduce spurious electrophysiological features. Consequently, they may compromise EEG signal quality, thereby reducing the reliability of downstream analyses. To address this issue, numerous EEG artifact removal methods have been developed, including both traditional denoising techniques and deep learning-based approaches. Traditional EEG denoising methods have long served as the primary solutions for artifact removal. Representative approaches include filtering, regression, and blind source separation. Although these methods have demonstrated effectiveness in specific scenarios, they suffer from several inherent limitations. Filtering assumes that artifacts and EEG signals can be separated in the frequency domain, but many artifacts, such as EOG and EMG, overlap with EEG spectra, which may lead to the loss of valuable neural information. Regression methods require high-quality artifact references to estimate and subtract contaminations, limiting their effectiveness in reference-free scenarios. Blind source separation can remove artifacts without external references, but it typically requires the number of EEG channels to exceed the number of sources, restricting its application in single- or low-channel EEG recordings. Deep learning-based EEG denoising methods address these limitations effectively. First, they learn the nonlinear mapping between contaminated and clean EEG directly from data in an end-to-end manner. This approach does not rely on assumptions about spectral separability, thereby preserving neural activity more completely. Second, the reference information is incorporated during the training phase, allowing the trained model to perform artifact removal independently without external references. Third, deep learning models can be flexibly designed to accommodate various recording setups, achieving robust denoising for both high-density and single-channel EEG. Collectively, these advantages enable deep learning-based methods to overcome the main challenges of traditional approaches, providing more accurate and reliable EEG signal recovery. The superior denoising performance of deep learning-based EEG denoising methods has attracted increasing attention in EEG artifact removal research. As a result, many deep learning-based denoising methods have been developed and successfully applied in neural engineering areas. However, a systematic review of the techniques and applications in this field is still lacking. To address this gap, this paper reviews recent advances in deep learning-based EEG denoising from four perspectives: technical principle, benchmark dataset, denoising model, and evaluation method. Representative applications in neural signal analysis and BCI decoding are also summarized. Furthermore, the advantage, existing challenge, and future research direction of deep learning-based EEG denoising are discussed. This review aims to provide valuable theoretical insights and technical guidance for researchers. It is also expected to promote further advances and broader applications of deep learning-based EEG denoising techniques.

Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

OBJECTIVE: To compare the clinical efficacy of acupuncture with yin-yang regulation method versus local acupuncture in treating chronic low back pain (CLBP) in elderly patients with lumbar disc herniation (LDH), and to evaluate the changes in the multifidus muscle before and after treatment using musculoskeletal ultrasound. METHODS: A total of 128 elderly patients with CLBP due to LDH were randomly assigned to an observation group (64 cases, 2 cases dropped out) and a control group (64 cases, 2 cases dropped out). The control group received local acupuncture at bilateral L₃-L₅ Jiaji points (EX-B2), Shenshu (BL23), Dachangshu (BL25), Weizhong (BL40), Yaoyangguan (GV3), and ashi points. The observation group received acupuncture with yin-yang regulation method, which included an abdominal protocol with Baihui (GV20), Zhongwan (CV12), Qihai (CV6), Guanyuan (CV4), bilateral Tianshu (ST25), and Dahe (KI12), etc., and a lumbar protocol with Baihui (GV20), Dazhui (GV14), Jizhong (GV6), Yaoyangguan (GV3), and ashi points, etc., alternated bilaterally. Both groups were treated once every other day, three times per week, for a total of 12 sessions. The visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and the indexs of musculoskeletal ultrasound multifidus muscle (resting and functional thickness and Young's modulus values) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After 1 and 4 weeks of treatment, both groups showed lower VAS scores compared to baseline (P<0.05), the VAS scores in the observation group were lower than those in the control group (P<0.001). ODI scores in both groups were decreased after 1 and 4 weeks of treatment compared to baseline (P<0.05), with a further reduction at 4 weeks of treatment compared to 1 week of treatment (P<0.05); the observation group showed lower ODI score than the control group after 1 week of treatment (P<0.001). After treatment, both groups demonstrated increased resting and functional multifidus muscle thickness bilaterally compared to baseline (P<0.01), with an increased right-side thickness change rate (P<0.01), though no significant difference was observed between groups (P>0.05). Compared to baseline, after treatment, the observation group exhibited decreased Young's modulus values for bilateral resting and functional multifidus muscle (P<0.01), while the control group showed reductions only in bilateral resting and right-side functional Young's modulus values (P<0.01). After treatment, the bilateral functional Young's modulus values in the observation group were lower than that in the control group (P<0.05), and the bilateral resting and functional changes in Young's modulus values were greater in the observation group than those in the control group (P<0.01). The overall effective rate was 93.5% (58/62) in the observation group, which was higher than 79.0% (49/62) in the control group (P<0.05). CONCLUSION Acupuncture with yin-yang regulation method effectively alleviates pain, improves functional disability, increases multifidus muscle thickness, and reduces Young's modulus values in elderly patients with CLBP due to LDH, which has superior therapeutic effect compared to local acupuncture.
Humans ; Low Back Pain/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Aged ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Yin-Yang ; Lumbar Vertebrae ; Acupuncture Points ; Treatment Outcome

Based on the theory of "three regions and sanjiao" in traditional Chinese medicine (TCM), the acupuncture-moxibustion differentiation and treatment system is explored and constructed for spasm syndrome, so as to provide a clearer guiding framework for TCM treatment of spasm syndrome. This disorder is caused essentially by the invasion of pathogenic wind, and located in brain marrow. The key regions of illness cover five zang organs and five tissues, and the core pathogenesis is associated with wind disturbance in brain marrow. In differentiation, spasm syndrome refers to overall transmission (from the upper to the lower) and local transmission (from exterior to interior). This disorder can be classified into sanjiao spasm (heart-lung spasm of the upper jiao, liver-spleen spasm of the middle jiao, and liver-kidney spasm of the lower jiao) and three-region spasm (skin-vessel spasm of the upper region, tendon-muscle spasm of the middle region, and tendon-bone spasm of the lower region). Based on "three regions and sanjiao" theory of acupuncture and moxibustion, 7 "expelling-wind" points can be selected in terms of the etiology of this disease. Baihui (GV20)-toward-Taiyang (EX-HN5) needling is applied to regulate the brain marrow, focusing on the core location of illness; and regarding the key location of illness, the combination of back-shu and front-mu points and that of jing-well and xing-spring points are adopted to regulate five zang organs. The five needling techniques (half needling, leopard-spot needling, joint needling, Hegu needling and shu needling) are used to regulate five tissues.
Humans ; Acupuncture Therapy ; Spasm/diagnosis* ; Moxibustion ; Acupuncture Points ; Medicine, Chinese Traditional ; Diagnosis, Differential

AIM: To investigate the correlation of serum Silent mating-type information regulation 2 homolog 1(SIRT1)and Vasostatin-2 content with pathological changes in diabetic retinopathy(DR)patients.METHODS: A total of 104 DR patients(104 eyes)admitted to our hospital from April 2021 to April 2024 were included as the DR group. According to different disease stages, they were assigned into a non-proliferative DR(NPDR)group of 44 cases(44 eyes)and a proliferative DR(PDR)group of 60 cases(60 eyes). Meantime, 104 patients(104 eyes)with simple diabetes were treated as non-DR group. ELISA was applied to detect the levels of SIRT1 and Vasostatin-2 in serum. The diagnostic value of serum SIRT1 and Vasostatin 2 in DR was analyzed by ROC curve. Multivariate Logistic regression was applied to analyze the factors that affected the occurrence of DR. Pearson correlation was applied to analyze the relationship between the levels of SIRT1 and Vasostatin-2 in the serum of DR patients and angiogenesis indicators(VEGF, Ang-2).RESULTS: Compared with the non-DR group, the levels of SIRT1 and Vasostatin-2 in the serum of the DR group were significantly decreased(P<0.05). Compared with the NPDR group, the levels of SIRT1 and Vasostatin-2 in the serum of the PDR group were significantly decreased(P<0.05). Compared with the non-DR group, the levels of VEGF and Ang-2 in the serum of the DR group were obviously higher(P<0.05). Compared with the single detection of serum SIRT1 and Vasostatin-2 levels, combined detection significantly increased the AUC in the diagnosis of DR(Z=4.180, 5.128, all P<0.05). Multivariate Logistic regression analysis showed that HOMA-IR(OR=3.455), fasting blood glucose(OR=1.467), SIRT1(OR=0.836), Vasostatin-2(OR=0.767), VEGF(OR=2.564), and Ang-2(OR=1.834)levels were the influencing factors on the occurrence of DR(all P<0.05). Pearson correlation analysis showed that the levels of SIRT1 and Vasostatin-2 in the serum of DR patients were negatively correlated with VEGF and Ang-2(rSIRT1 vs VEGF=-0.395, rSIRT1 vs Ang-2=-0.474, rVasostatin-2 vs VEGF=-0.323, rVasostatin-2 vs Ang-2=-0.583, all P<0.001).CONCLUSION: The abnormal decrease of serum SIRT1 and Vasostatin 2 levels in DR patients is closely related to the stage of DR lesions and angiogenesis.