OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Image 1.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Objective To explore the correlation between gallbladder stones and small intestinal bacterial overgrowth(SIBO).Methods A retrospective analysis was conducted on the clinical data of 393 patients who attended the Department of Gastroenterology of the Sixth Medical Center of Chinese PLA General Hospital from January 2021 to September 2023.They were divided into gallbladder stones group(n=190)and control group(n=203)based on the presence of gallbladder stones.Their general clinical data,laboratory test results,and abdominal symptoms were compared.Multivariate logistic regression was used to analyze the risk factors for gallbladder stones.Additionally,the total population was divided into SIBO-positive group(n=239)and SIBO-negative group(n=154),and their clinical characteristics were analyzed by logistic regression to explore the risk factors for SIBO.Results Univariate analysis revealed that gallbladder stones group had a higher rate of age,body mass index(BMI),fasting plasma glucose(FPG),glutaminase levels,prevalence of hypertension,diabetes,coronary heart disease,non-alcoholic fatty liver disease,gallbladder polyps,and SIBO,as well as a higher prevalence of CH4-positive and H2-positive in SIBO group than control group(P＜0.05).In terms of abdominal symptoms,the incidence of bad breath(48.4%vs.35.5%),dyspepsia(38.4%vs.28.6%),abdominal pain(30.5%vs.14.8%),bloating(42.1%vs.28.6%),diarrhea(20.5%vs.7.4%),and more exhaustion(46.8%vs.34.5%)were significantly higher in gallbladder stones group than those in control group(P＜0.05).Multivariate logistic regression analysis showed that independent positive determinants for incident gallbladder stones were age,BMI,FPG,total bilirubin(TBIL),coronary heart disease,gallbladder polyps,and SIBO.Univariate analysis revealed that age,prevalence of gallbladder stones,proportion of single stones,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were significantly higher in SIBO-positive group than those in SIBO-negative group(P＜0.05).Multivariate logistic regression analysis showed that the risk factors for SIBO were age,coronary heart disease,and gallbladder stones,while the protective factor for SIBO was high-density lipoprotein cholesterol(HDL-C).Conclusion There is a significant correlation between gallbladder stones and small SIBO;interventions on related factors of gallbladder stones and small SIBO may help reduce their incidence.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.

This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.

Objective To explore the application effect of blood pressure management based on the health belief model in patients with moyamoya disease after cerebral vascular reconstruction sur-gery.Methods From February to July 2024,210 patients with moyamoya disease who underwent cerebral vascular reconstruction surgery in our hospital were selected as study subjects.They were randomly divided into control group and intervention group,with 105 cases in each group.The control group received routine nursing care,while the intervention group applied blood pressure management based on the health belief model on the basis of routine nursing care.The postoperative cerebral hy-perperfusion syndrome and blood pressure control status of the two groups were compared,and the Health Belief Scale and the Mishel Uncertainty in Illness Scale were used to evaluate the effects before and after intervention.Results A total of 203 patients completed the study,including 100 cases in the control group and 103 cases in the intervention group.There were statistically significant differ-ences in the incidence of cerebral hyperperfusion syndrome and the proportion of patients with blood pressure higher than baseline data between the two groups(P＜0.05).After the intervention,there were statistically significant differences in the postoperative cerebral hyperperfusion syndrome status and blood pressure control status between the two groups(P＜0.05).After intervention,there were statistically significant differences in the scores of susceptibility and health motivation dimensions as well as the total score in the Health Belief Scale between the intervention group and the control group(P＜0.05).After the intervention,there were statistically significant differences in the scores of ambiguity and unpredictability dimensions as well as the total score in the Mishel Uncertainty in Ill-ness Scale between the intervention group and the control group(P＜0.05).Conclusion Blood pressure management based on the health belief model can effectively control blood pressure,reduce the incidence of cerebral hyperperfusion,improve health beliefs,and reduce the sense of uncertainty about the disease.