Objective: To assess the causal association between specific oral microbiota and the risk of oral leukoplakia (OLK) using a Mendelian randomization (MR) approach, and to elucidate the potential mediating role of immune cells. Methods: Summary statistics from genome-wide association studies (GWAS) of the oral microbiome, GWAS data for immune cell phenotypes, and GWAS summary statistics for OLK from FinnGen were used. The inverse variance weighted (IVW) method was adopted as the primary approach, and it was supplemented by MR Egger regression, simple mode, weighted median, and weighted mode methods for additional analyses, to investigate the causal relationship between 3 117 types of tongue coating and salivary microbiota, as well as 731 immune cell traits, and OLK. Furthermore, a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK. Results: IVW analysis revealed causal associations between 15 oral microbial genera and OLK. Among these, Streptococcus, Neisseria, and Catonella were associated with a reduced risk of OLK, with Fusobacterium showing the most significant protective effect (OR = 0.41, P = 0.023). In contrast, genera, including Microbacterium, Campylobacter, and Haemophilus_A, were linked to an increased risk of OLK, with Lancefieldella exhibiting the strongest risk effect (OR = 2.66, P = 0.006). Eleven immune cell phenotypes with potential causal associations with OLK were identified, including four protective and seven risk-increasing factors. Mediation analysis further identified four key mediating pathways: pathogenic genera, particularly Campylobacter_A and Lancefieldella, may promote the development and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes, B cells, and myeloid cells. Conversely, the potentially protective genus Catonella appeared to exert inhibitory effects on OLK by significantly downregulating dendritic cell subsets. Conclusion This study is the first to reveal, at the genetic level, causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses. These findings provide novel insights into the immunopathological mechanisms underlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or immune cell subsets.

ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Minimally conscious state （MCS） is at the edge between closed and open consciousness， but it still belongs to the category of "wind-strike block" syndrome. The basic pathogenesis of MCS is the obstruction of pathogenic qi， orifices closed and spirit hidden， with pathological factors including phlegm， fire， and blood stasis. Wind movement and water retention may also be present， and often leading to deficiency syndrome due to the exhaustion of qi， blood， yin， and yang at later stages. Treatment chooses Shexiang （Moschus） as the chief medicinal， emphasizing combination of medicinals and urgency of medication administration； the key therapeutic method is to open the orifices， with focuses on expelling pathogens and reinforcing healthy qi. For patients with severe phlegm or fire， use Xiaochengqi Decoction （小承气汤） to open the lower orifices， discharge heat and unblock the bowels， combined with Shexiang （Moschus） and Niuhuang （Bovis Calculus） to open the upper orifices， awaken the spirit and guide qi. For patients with turbid phlegm as the predominant， temporarily replace Shexiang （Moschus） with Baizhi （Angelicae dahuricae radix）， using Ditan Decoction （涤痰汤） to eliminate phlegm to open the orifices， when turbid phlegm gradually subsided， Shexiang （Moschus） could be added. For patients with blood stasis as the predominant， Tongqiao Huoxue Decoction （通窍活血汤） will be used to activate blood and open orifice， if the blood circulates， the endogenous wind will be calmed， the water will be induced， the orifices will open and the consciousness will restore. For patients with closed orifices and body deficiency， the treatment should open the orifices and reinforce healthy qi， and consider the root and branch simultaneously； qi deficiency syndrome can be addressed with Buyang Huanwu Decoction （补阳还五汤） to boost qi and reinforce healthy qi； yin deficiency syndrome can be treated with Shaoyao Gancao Decoction （芍药甘草汤） combined with Fengsui Pill （封髓丹） to nourish yin， soften sinews， and secure kidney essence； yang deficiency can be managed by using Dihuang Yinzi Decoction （地黄饮子） to enrich yin， supplement yang， and open the orifices.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Alzheimer's disease （AD） is a chronic neurodegenerative disorder characterized by the progressive loss of cognitive and memory functions. Its pathological features mainly include neurofibrillary tangles formed by the aggregation of hyperphosphorylated tau proteins and amyloid plaques formed by the accumulation of β-amyloid. The exact pathogenesis of AD has not been fully elucidated， and there are currently no effective specific drugs or radical treatments available in clinical practice. In recent years， the incidence of AD has been on the rise， severely affecting life and health， making the search for effective drugs and therapeutic components for AD treatment crucial. Modern medical research has found that the brain-derived neurotrophic factor （BDNF）/tropomyosin receptor kinase B （TrkB） signaling pathway is closely related to neurogenesis， apoptosis， neuroinflammation， synaptic plasticity， and oxidative stress， playing a vital role in the pathophysiological development of AD. Additionally， Chinese medicine has a long history of treating neurodegenerative diseases with few adverse reactions and features a multi-target， multi-link， and multi-pathway approach to treatment. Therefore， the author reviewed the latest research reports in China and abroad to elaborate on the role of the BDNF/TrkB signaling pathway in the onset and progression of AD， and summarized the research progress on the regulation of the BDNF/TrkB pathway by Chinese medicine compounds and monomers in AD intervention. This study is expected to provide references for the development of clinical drugs for the prevention and treatment of AD and to broaden the perspective on Chinese medicine treatment of AD.

It is regarded that the general qi is the combination of spleen-kidney qi and heart-lung yang qi in the chest， which is filled between the muscles and is able to maintain the normal shape of the muscles. Accordingly， it is proposed that the core pathogenesis of amyotrophic lateral sclerosis （ALS） is the deficiency sinking of general qi， with "deficiency" as the root， and "toxin" and "wind-heat" as the key factors for the rapid progression of the disease. The development process of ALS was classified into the initial onset stage， the increasingly progressive stage， and the rapid exacerbation stage， and differentiated and treated by deficiency， toxin， and wind-heat. Based on clinical experience， the wind medicinals were preferred. We formed self-prescribed Juxian Decoction （举陷汤） and modified from the perspective of "deficiency， toxicity， wind-heat" based on the wind medicinals of Huangqi （Radix Astragali）， Shengma （Actaea cimicifuga L.）， Chaihu （Bupleurum spp.） and so on. For the initial onset stage， Yiqi Shengji Juxian Decoction （益气生肌举陷汤）， Wenyang Liyan Juxian Decoction （温阳利咽举陷汤） could be used； for the increasingly progressive stage， Jiedu Juxian Decoction （解毒举陷汤） could be used； for the rapid exacerbation stage， Yinqiao Shufen Juxian Decoction （银翘疏风举陷汤）， Yangxue Xifeng Juxian Decoction （养血熄风举陷汤） could be used.

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Chaihu Guizhi Decoction is an excellent prescription of ZHANG Zhongjing;however,nowadays the application of Chaihu Guizhi Decoction is primarily derived from the text.The xiang thinking is the source of traditional Chinese medicine thinking.Understanding Chaihu Guizhi Decoction from the xiang thinking,it is easy to perceive the true meaning of ZHANG Zhongjing,and grasp the location of the disease and the patient's overall qi,so as to make better use of this formula.This article discusses the understanding of Chaihu Guizhi Decoction from five perspectives:firstly,it gives an overview of the xiang thinking,pointing out the source and essential value of the xiang thinking;secondly,it analyses the disease position and the patient's qi of Chaihu Guizhi Decoction under the perspective of the xiang thinking as a whole;thirdly,it discusses the disease position and the patient's qi of the original text of Chaihu Guizhi Decoction from the xiang thinking;fourthly,it discusses how to understand the principle of formula formation and the main and minor parts of Chaihu Guizhi Decoction by xiang thinking;finally,it analyses the primary medicines in Chaihu Guizhi Decoction by using xiang thinking based on the records of Shennong Bencao Jing.Based on these five points,we hope to reveal the traditional Chinese medicine thinking behind Chaihu Guizhi Decoction,and provide new ideas for the clinical application of Chaihu Guizhi Decoction.

This article summarizes the unique viewpoints and experience application of the famous and veteran Chinese medicine practitioner,Professor Wang Xinzhi,in treating emotional diseases from the perspective of gallbladder theory.Based on the physiologi-cal functions and characteristics of the gallbladder in Chinese medicine,it is proposed that the"heart mind-gallbladder-viscera"axis dominates the generation and changes of emotions,and it is believed that gallbladder failure is the key pathogenesis of emotional disor-ders.The treatment of clinical syndromes should be based on the type of gallbladder,and emotional diseases can be divided into types of insufficient gallbladder qi,unfavorable Shaoyang,gallbladder and heat excess,timidity-deficiency,and heart-gallbladder indeci-sion,according to clinical manifestations;based on the basic principle of adjusting the functions of the heart,spleen,liver,gallblad-der,kidney and other organs,treatment methods such as tonifying the spleen and kidneys,increasing gallbladder qi,resolving Shaoy-ang,clearing gallbladder heat,warming yang and replenishing qi,calming the mind,resolving phlegm and removing blood stasis should be used,highlighting the joint treatment of the heart and the gallbladder,and the simultaneous regulation of the liver and gall-bladder,so that the mind can be at ease,the gallbladder can be decisive,and the emotions can be harmonious.