OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis （UC） through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor （AhR） axis. METHODS Mice were randomly divided into normal group （normal saline）， model group （normal saline）， microbiota depletion-model group （normal saline）， microbiota depletion-Huangqin decoction group （9.1 g/kg， by crude drug， similarly hereinafter）， Huangqin decoction group and mesalazine group （positive control group， 0.4 g/kg）， with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling， each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration， body weight change ratio， disease activity index （DAI） score， and colon length were evaluated； colon pathological changes were observed； serum levels of interleukin-6 （IL-6）， IL-10， IL-22， and tumor necrosis factor-α （TNF-α） were measured； the expressions of Occludin， zonula occluden-1 （ZO-1）， and AhR in colon tissue were detected； fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group， Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio， colon length， serum content of IL-10， the expressions of Occludin， ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid （IPA）， N -acetylserotonin （NAS） and indole-3-acetic acid （IAA） were all significantly increased （ P ＜0.05）； DAI score， serum levels of IL-6， TNF-α， and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased （ P ＜0.05）； gut microbiota structure was improved， with increased relative abundances of beneficial bacteria such as Lactobacillus ， and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However， after antibiotic-induced microbiota depletion， although Huangqin decoction significantly increased the content of NAS in the feces of mice， the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA， thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Idiopathic pulmonary fibrosis （IPF） is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs， which have poor efficacy and induce side effects， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation （macrophage polarization）， oxidative stress， epithelial-mesenchymal transition （EMT）， autophagy inhibition and other related signaling pathways， while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM， lung collateral obstruction is the basic pathogenesis of IPF. Therefore， according to the principle of dredging and replenishing lung collaterals， IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen， replenishing qi and activating blood， and detoxifying and dredging collaterals， which demonstrate definite curative effect and can effectively relieve clinical symptoms， restore the lung function and blood oxygen partial pressure， improve the quality of life of patients， and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation （macrophage polarization）， oxidative stress， EMT， autophagy inhibition and other signaling pathways. Therefore， from the perspective of impediment， this article reviews pathogenesis of IPF， the research progress in TCM treatment of IPF， and the treatment of IPF from active components， single herbs， and compound prescriptions of TCM， with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

Diabetic macular edema(DME), a serious complication of diabetic retinopathy(DR), is a chronic condition caused by multiple factors. Throughout its progression, inflammatory factors and vascular endothelial growth factor(VEGF)play a critical role. Anti-VEGF drugs have shown significant effectiveness in the treatment of DME; however, some patients may experience persistent DME after injection or require frequent injections. Dexamethasone intravitreal implants(DEX implants)serve as a sustained-release implant characterized by a reasonable release profile and high bioavailability. They offer safe, effective, and prolonged anti-inflammatory effects, aiding in the repair of retinal barrier and reduction of exudation. To further enhance patients' visual quality, exploring the efficacy of DEX implants in combination with existing treatment regimens has great clinical significance. This review primarily discusses the research advancements in DEX implants, focusing on their pharmacological properties, indications for use, and their combination with existing drugs and treatment methods. It also evaluates the advantages and disadvantages of combination therapy or switching to DEX implants compared to current standard treatments, aiming to provide guidance for personalized treatment options for patients with DME.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome