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.

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.

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.

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.

Objective To compare the efficacy and safety of stellate ganglion block(SGB)with those of conventional western medication in the treatment of insomnia.Methods A computerized retrieval of academic papers concerning the clinical randomized controlled trials of SGB versus conventional western medication in the treatment of insomnia from the databases of PubMed,Embase,Cochrane Library,CNKI,Wanfang Data knowledge service platform,VIP database and CBM database was conducted.The retrieval time period was from the establishment of the database to June 13,2023.NoteExpress v3.5 software was used to make literature screening,Stata17.0 software was used to perform meta-analysis of the obtained data,TSA0.9.5.10 beta software was used to make sequential analysis,and GRADEpro was used to perform the grade classification.Results A total of 11 articles including 875 patients with insomnia were included in this analysis.Compared with the conventional western medication,SGB showed certain advantages in the following aspects:improving total clinical effectiveness(RR total=1.24,95％CI:1.16-1.32,P＜0.01),increasing the proportion of patients who could sleep for more than 3 hours after treatment(RR total=1.24,95％CI:1.09-1.41,P=0.001),increasing total sleep time(SMD=1.53,95％CI:0.89-2.16,P＜0.01),reducing sleep latency(MD=-14.08,95％CI:-18.72--9.43,P＜0.01),decreasing PSQI score(MD=-3.54,95％CI:-4.31--2.78,P＜0.01),and reducing the recurrence rate within 6 months(RR=0.19,95％CI:0.10-0.37,P＜0.01).However,the difference in the proportion of patients who could sleep for more than 6 hours after treatment between the two groups was not statistically significant(RR=1.31,95％CI:0.97-1.76,P=0.078).The traditional SGB therapy had a certain risk of adverse events,ultrasound-guided SGB therapy was much safer.Trial sequential analysis showed that the cumulative sample size of the effective rate crossed the conventional threshold and TSA threshold,the positive results had been obtained in advance although it did not reach RIS.The quality of evidence evaluated by GRADE for the sleep latency,PSQI and recurrence rate within 6 months was medium grade,and the quality for the remaining indexes was low grade.Conclusion Compared with conventional western medication for the treatment of insomnia,the effect of SGB in increasing the total response rate,the proportion of patients who get sleeping for more than 3 hours after treatment and the total sleep duration,in reducing sleep latency,PSQI score and recurrence rate within 6 months has gained some certain evidence supports.The SGB and conventional western medication have similar efficacy in improving the proportion of patients who get sleeping for more than 6 hours after treatment.The results of this study are stable and reliable,but the current level of evidence grade is lower,therefore,large-sample randomized controlled trials need to be conducted before its clinical efficacy can get further evidence-based support.

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.

The uncertainty of prognosis for chronic diseases is a persistent problem in the medical community.Mechanical attribution such as questioning disease （stubbornness）， equipment （medical and nursing level）， and patients （low compliance）， it is believed that there is a bias in analyzing the deep causes of low compliance on prognosis after breakthrough progress in the treatment of this type of diseases.Taking hepatitis B patients from the perspective of hermeneutics as an example， this paper clarified the reasons for the non-identity of doctor-patient cognition on the problem of doctor-patient communication in health education.Meanwhile， it was found that there is a pre-structure of heterogeneous experience in the ontology of understanding between doctors and patients， which presents inherent limitations， openness， generativity， and external micro power penetration in their history of dialogue logic.Finally， epistemologically， this paper clarified the essence such as the history of identity effect was pointed by the reconstruction of heterogeneous “meaning ideals” of doctors and patients， the understanding of certainty and elimination of subjectivity was guided by meaning ideals under the fusion of horizons， as well as good personalized prognostic behavioral literacy was led by cultivations of embodied practice.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Post-stroke depression is a common complication after a stroke. Based on the theory of ＂deficiency of heart qi leading to sadness＂recorded in Huangdi Neijing, our team proposes that deficiency of heart qi is the basic pathogenesis of post-stroke depression, with sadness being its main manifestation. Therefore, we advocate treating post-stroke depression from the perspective of the heart, and clinically, it can be divided into four stages: heart-liver stage, heart-lung stage, heart-spleen stage, and heart-kidney stage. Treating post-stroke depression with the principle of regulating qi and nourishing the heart, patients in the heart-liver and heart-lung stages are mainly middle-aged and young adults, with a pathological nature of qi stagnation and mild deficiency of heart qi, and therefore, the method of promoting the flow of meridians and regulating qi should be adopted. In contrast, patients in the heart-spleen and heart-kidney stages are mainly middle-aged and elderly, with a pathological nature of qi deficiency and severe deficiency of heart qi, and therefore, nourishment and tonification should be prioritized. In response to the above four stages, our team has achieved good clinical efficacy by administering Xiaoyao Powder, Baihe Dihuang Decoction, Ganmai Dazao Decoction and Jingui Shenqi Pill respectively. This study discusses the approach to treating post-stroke depression from the perspective of a "deficiency of heart qi leading to sadness" by examining three aspects: the theoretical basis of Chinese and Western medicine to treat post-stroke depression from the heart, the basic pathogenesis and staging of post-stroke depression, and the treatment principle of regulating qi and nourishing the heart. The study also briefly analyzes the clinical experience of the medications used for this condition to provide a reference for the treatment of post-stroke depression.