OBJECTIVE:Traditional Chinese medicine (TCM) has been widely used in assisted reproduction, but the outcomes have been inconsistent. This study evaluated the impact of sequential TCM treatment on pregnancy outcomes among patients undergoing intrauterine insemination (IUI). METHODS:This retrospective cohort study included female patients who underwent IUI with their husband's sperm at the Reproductive Center of Affiliated Hospital of Shaanxi University of Chinese Medicine between November 2019 and June 2022. Patients were divided into sequential TCM (TCM was administered for at least 14 consecutive days during the treatment cycle) and non-sequential TCM (TCM was administered for fewer than 14 days or not administered) groups according to the duration of TCM administration. The primary outcomes were clinical pregnancy rate and live birth rate. RESULTS:A total of 396 cycles were analyzed, with 160 cycles undergoing sequential TCM treatment. The sequential TCM group exhibited a higher clinical pregnancy rate (26.3% vs 14.0%, P = 0.002) and live birth rate (20.0% vs 10.2%, P = 0.006) compared to the non-sequential TCM group. After adjusting for endometrial pattern and dominant follicle diameter, the odds ratios for pregnancy and live birth in the sequential TCM group were 2.289 (95% confidence interval [1.335, 3.923], P = 0.003) and 2.241 (95% confidence interval [1.226, 4.096], P = 0.009), respectively. CONCLUSION:In this retrospective cohort, sequential TCM treatment was associated with higher clinical pregnancy and live birth rates in patients undergoing IUI treatment. Please cite this article as: Li N, Yan XL, Wang LJ, Zhang H, Chen M, Bai J, Ji N, Zhang YD, Pang Y, Wang HJ. Impact of sequential traditional Chinese medicine intervention on pregnancy outcomes of intrauterine insemination: A retrospective cohort study. J Integr Med. 2026; 24(3):387-393.
Background:The incidence of nonalcoholic fatty liver disease(NAFLD)is increasing.Yinchenhao Decoction(YCHD)has been well studied for its uses in treating NAFLD.Moreover,the metabolism of bile acids(BAs)and eicosanoids have influence on NAFLD.YCHD is a classic prescription for damp-heat syn-drome,and can regulate BA metabolism and alleviate inflammation in NAFLD. Objective:This study evaluated the effects of YCHD on NAFLD and explored the effect of YCHD on eico-sanoids and BAs. Design,setting,participants and interventions:This randomized,double-blind,placebo-controlled trial enrolled 130 NAFLD participants.The participants were randomly assigned to YCHD group or placebo group in a 1:1 ratio,receiving YCHD granules or the placebo for 24 weeks. Outcome measures:Primary outcome was absolute change in liver magnetic resonance imaging proton density fat fraction(MRI-PDFF)from the baseline to week 24.Secondary outcomes included absolute changes in controlled attenuation parameter(CAP),metabolic parameters,and liver injury and function parameters. Results:After 24 weeks of treatment,MRI-PDFF(average),CAP,alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and body mass index(BMI)decreased significantly in the YCHD group compared to placebo group(all P<0.05).Moreover,no serious adverse events were observed.Further,YCHD did not significantly regulate eicosanoids(all P>0.05);however it did regulate taurodeoxycholic acid(TDCA),glycodeoxycholic acid(GDCA),deoxycholic acid(DCA),glycolithocholic acid(GLCA),and the ratio of GDCA to total BAs,compared to the placebo at week 24(P<0.05). Conclusion:YCHD can reduce the MRI-PDFF,CAP,ALT,AST,ALP and BMI without significant adverse events.YCHD can also regulate the metabolism of TDCA,GDCA and DCA,and the ratio of GDCA to total BAs.
OBJECTIVE:Lily bulb, derived from the root of Lilium lancifolium Thunb. (Liliaceae), is a commonly used medicinal material and dietary supplement for climacteric syndrome. This study investigated the effects of total saponins from lily bulbs (TSLB), one of the main biologically active ingredients, on cognitive and mood disorders during menopause, as well as the underlying mechanisms of these effects. METHODS:C57BL/6N mice underwent either ovariectomy (OVX) or sham surgery. After a recovery period of 2 weeks, these mice were exposed to chronic unpredictable mild stress (CUMS) for the subsequent 2 weeks, followed by multiple behavioral tests. Immediately after OVX, TSLB were administered at doses of 12, 24 and 48 mg/(kg∙d) by oral gavage for 36 d. Western blotting was used to assess the effects of TSLB on neurotransmitter modulators, neurotrophins and estrogen receptors (ERs). RESULTS:At the dose of 24 mg/(kg∙d), TSLB exhibited anxiolytic activity evidenced by an increase in the duration in the elevated plus maze test (P = 0.003), antidepressant activity demonstrated by a decrease in immobility time in the tail suspension test (P = 0.047), and cognition-improving activity demonstrated by an increase in time spent in the target zone in the Morris water maze test (P = 0.039). These results were attributed to the predominant activation of ERs through direct binding of TSLB, with a higher affinity to ERβ than to ERα, as well as the regulation of neurotransmitters and neurotrophins in the brain. CONCLUSION:TSLB alleviated cognitive deficits and anxiety-like and depression-like behavior in OVX mice exposed to CUMS, suggesting the potential of TSLB as a novel treatment for menopause-related neuropsychological disorders. Please cite this article as: Zhou XD, Qin ZS, Shi DD, Chiang CY, Zhang ZJ. Anxiolytic, anti-depressive and cognition-enhancing effects of total saponins from lily bulbs in ovariectomized mice: A potential therapy for menopause-associated emotional disorders. J Integr Med. 2026; 24(3):403-414.
OBJECTIVE:This study evaluated the effectiveness of acupuncture for improving pregnancy outcomes, endometrial receptivity (ER), and embryo transfer success in patients with recurrent implantation failure (RIF). METHODS:A retrospective cohort study was conducted using the medical records of 609 RIF patients undergoing frozen embryo transfer between January 2019 and June 2022. Patients were divided into two groups: those receiving acupuncture combined with hormone replacement therapy (HRT) or delayed HRT (d-HRT) and those receiving only HRT/d-HRT. Propensity score matching (PSM) ensured comparability between the groups. Clinical outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and biochemical pregnancy rate (BPR), were analyzed. Endometrial thickness, hormonal levels and uterine blood flow were also assessed. RESULTS:After PSM, 166 patients were included in each group. The acupuncture group demonstrated significantly higher CPR (36.5%), LBR (28.0%), OPR and BPR compared to the control group (P < 0.05). Endometrial thickness, and estradiol and progesterone levels were also significantly higher, while uterine resistance and pulsatility indices were lower in the acupuncture group (P < 0.05). Predictors of live birth included patient age (< 35 years, hazard ratio [HR] = 0.933, P = 0.002), body mass index (BMI) (< 24 kg/m2, HR = 0.974, P = 0.046), anti-Müllerian hormone (AMH) level (> 2 ng/mL, HR = 1.021, P = 0.043), high-quality embryo transfers (HR = 1.670, P < 0.05), and transferring two embryos (HR = 1.181, P < 0.05). CONCLUSION:Acupuncture significantly enhanced ER and improved LBR in RIF patients. Younger patients with lower BMI, higher AMH level, and high-quality or dual embryo transfers benefited most from this complementary therapy. Please cite this article as: Li HZ, Wu YJ, Li XR, Deng B, Pang YX, Lin SY, Lu LM, Li YM. Enhancing pregnancy outcomes in recurrent implantation failure: The role of acupuncture in improving endometrial receptivity. J Integr Med. 2026; 24(3):394-402.
Chinese herbal traditions, with a history of over 2000 years, emphasise the harmony between spirit, body and nature. Integrating these principles with machine learning (ML) offers transformative potential for traditional Chinese medicine (TCM). By leveraging technologies and data-driven models, TCM can evolve while preserving its accumulated wisdom. Knowledge graphs combined with deep learning can enhance diagnosis, treatment planning and prognosis evaluation. This paper reviews current ML applications in TCM and strategies for integration with conventional practices. It categorises key challenges and proposed solutions, focusing on deep learning-based algorithms. ML has demonstrated success in automating personalised herbal prescriptions, predicting diagnostic outcomes and identifying acupoints. However, major obstacles include data standardisation, ethical and legal frameworks, and fostering interdisciplinary collaboration. The development of high-quality, ethical artificial intelligence requires regulatory support and cooperation with TCM practitioners. This study supports the notion that a learning platform is essential for the education of TCM practitioners. ML and TCM may adopt this implementation approach, and the emergence of convex ML can substantially enhance testing algorithms in TCM, hence improving the effectiveness of future healthcare systems. Please cite this article as: Huang X, Goh HH, He TT, Zhang DD, Dai W, Kurniawan TA, Goh KC, Wong HY, Islam MT, Liang X. Integration of traditional Chinese medicine and machine learning: Opportunities, obstacles, and implications for future of healthcare. J Integr Med. 2026; 24(3):295-309.
Invasive laser acupuncture (ILA) is an innovative integration of traditional acupuncture with precise laser stimulation delivered directly into acupoints, yet it is not widely used in clinical practice and lacks extensive clinical studies. In the era of digital healthcare and patient-specific treatment, computational predictive models have become essential tools for optimizing medical procedures and ensuring treatment safety. However, existing computational models for laser-based therapies primarily focused on skin surface treatments or ablation procedures, creating a significant gap in understanding unique characteristics of ILA. This study addressed this challenge by developing and validating a novel computational predictive model that incorporates the geometric characteristics of needle-integrated optical fiber delivery. The model was validated through ex vivo experiments using a 650 nm laser device, demonstrating good agreement in temporal temperature changes at the irradiation point with an average difference of 11.6%. Using this validated model, systematic investigation of ILA responses to varying laser parameters was conducted to analyze the photothermal effects in tissue. These quantitative insights into the relationships between laser parameters and photothermal responses provided a foundation for evidence-based selection of treatment parameters. This computational framework contributes to the advancement of ILA therapy by enabling more precise control of therapeutic outcomes and supporting the development of safety protocols. Please cite this article as: Kim HJ, Kim J, Kim JG, Lee S, Chae Y, Lee IS. Photothermal effect of invasive laser acupuncture: A computational study with experimental validation. J Integr Med. 2026; 24(3):352-364.
Biomedical science has long been based on a reductionist approach, attributing diseases to specific molecular or pathway abnormalities. However, for complex diseases caused by multiple interrelated biological dysfunctions, the static, localized and linear approach struggles to fully capture the biological essence of diseases, which makes it challenging to form effective therapeutic strategies. In contrast, traditional Chinese medicine (TCM) theory offers distinct advantages. TCM identifies the comprehensive pathological state of the human body centered on the concept of syndrome differentiation; it employs systematic regulatory methods and emphasizes the prevention of syndrome progression. This approach embodies both systemic and dynamic perspectives, thereby achieving great therapeutic outcomes for complex diseases. Nevertheless, current research on TCM syndromes has predominantly relied on a reductionist framework, interpreting syndromes merely as abnormalities in molecular expression levels; this limits the appreciation of their inherent systemic and dynamic characteristics. To address this issue, we propose an integrative perspective that is grounded in TCM syndrome theory while employing a nonlinear dynamical systems approach to disease understanding. In this paper, we first elucidate the state-medicine characteristics that are inherent in TCM theory; then we discuss how TCM syndromes align with the properties of an attractor in complex dynamical systems, proposing that TCM syndromes represent pathological attractor states of the human system; finally, we conceptualize a syndrome attractor in the system of the human body and elaborate on its value in modern medicine. This concept introduces the analytical methods of nonlinear dynamics into the study of TCM syndromes, enabling a more comprehensive elucidation of their systemic and dynamic biological basis. It bridges TCM syndrome differentiation and intervention methods with complexity science, thereby offering a new approach for integrating the holistic and systematic views of TCM with biomedical research. This study aimed to promote a dynamic systems-level understanding of diseases in modern medicine, while providing a reference for addressing current challenges for complex and refractory diseases. Please cite this article as: Zhao ZW, Li WY, Li WZ, Wang Y. Syndrome attractors: Providing a system dynamics view of disease from the integrative medicine perspective. J Integr Med. 2026; 24(3):287-294.
Atopic dermatitis (AD) is the most common chronic inflammatory skin condition. It has significant socioeconomic consequences and complex pathophysiology, necessitating updated management guidelines that consider the age, sex and geographic location of patients. Despite the widespread use of Western medicine (WM), including topical corticosteroids, as the primary treatment for AD, the possible negative effects of WM therapies are inescapable. Although there is still a lack of strong evidence, the integration of traditional Chinese medicine (TCM) with WM may yield a more favorable therapeutic response for AD than WM alone, due to the synergistic effects involved. Balancing the application of diagnostic and therapeutic approaches from TCM and WM is crucial for the management of AD, enhancing treatment efficacy for patients, and averting disease recurrence. In 2025, a new clinical guideline for the diagnosis and treatment of AD was released; it emphasized the integration of TCM with WM. This guideline is crucial as it consolidates global expertise and data to provide a standardized framework for the practical integration of techniques to bridge divides among clinical disciplines. As more substantial data emerge, the development and enhancement of integrative medicine for AD management should be prioritized globally, particularly in Asian regions. Please cite this article as: Chen M, Liao WQ. Atopic dermatitis management in the era of integrative medicine. J Integr Med. 2026; 24(2):137-139.
OBJECTIVE:We developed a novel silk fibroin@polydopamine (SF@PDA) material and investigated the mechanism of SF@PDA acupoint implantation for the treatment of Alzheimer's disease (AD) in a mouse model. METHODS:In the materials research phase, we characterized the surface morphology and properties of the novel SF@PDA composites and evaluated their safety using the cell counting kit-8 assay. Following the intervention, C57BL/6 mice underwent open-field experiments and the Morris water maze test. We analyzed the collected tissues with hematoxylin-eosin staining, immunofluorescent staining, Western blotting, reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS:After acupoint implantation, SF@PDA reduced amyloid-β (Aβ) deposition and preserve neurons, thereby improving cognitive performance. In particular, SF@PDA can reduce the expression of inflammatory factors, including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α, and inhibit the inflammatory response, thereby further reducing Aβ accumulation and neuronal damage. The SF@PDA treatment resulted in an increase in exploratory behavior and a decrease in the number of errors in mice. Meanwhile, the number of Aβ plaques in the brain was significantly reduced (P < 0.05), and inflammatory cell infiltration was lessened. CONCLUSION:SF@PDA acupoint implantation has significant therapeutic effects on AD model mice. The mechanism can be related to the inhibition of inflammatory response, reduction of Aβ deposition, and promotion of nerve regeneration. Please cite this article as: Wang C, Liu X, Fan Y, Liu GY, Wu P, Li SC, Du YJ. Silk fibroin@polydopamine for acupoint catgut-embedding therapy in Alzheimer's disease. J Integr Med. 2026; 24(3):415-428.
Over the past decade, the prevalence of hepatic disorders has shown a steady upsurge, raising serious public health concerns. Alcohol consumption, indiscriminate use of medications, a high-calorie diet and exposure to viral infections are all thought to be the primary risk factors for developing hepatic diseases. Due to the lack of effective treatments for hepatic disorders, such as metabolic dysfunction-associated fatty liver disease, alcoholic liver disease, liver fibrosis, cirrhosis and liver cancers, and the numerous side effects of existing therapies, medicinal plants are receiving increased attention as an alternative treatment for hepatic disorders. Iridoids are bitter-tasting secondary metabolites found in many medicinal plants. Numerous in vitro and in vivo studies have demonstrated that iridoids or extracts containing iridoids produce hepatoprotective effects by targeting inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction. This comprehensive review discusses scientific research on the hepatoprotective effects of various iridoids and the targeted pathways involved in liver disorders. Research data on iridoids as hepatoprotective molecules were obtained through multiple databases such as ScienceDirect, Web of Science, PubMed, Wiley Online Library and Scopus using relevant keywords such as iridoids and hepatoprotective. Based on the available information, further research is required for the optimization of the targeted delivery of iridoids in therapeutic and toxicity studies and randomized clinical trials in humans. Please cite this article as: Dogra S, Patial V. Iridoids in liver diseases: Mechanistic insights and molecular mechanism. J Integr Med. 2026; 24(3):310-326.
OBJECTIVE:This study develops a core outcome set (COS) for clinical research concerning Chinese medicine (CM) dampness syndrome (COS-CMDS) that might improve heterogeneity of outcomes, reporting, and inadequate attention to the CM characteristic outcomes in clinical research on CM dampness syndrome. METHODS:An initial outcome pool was constructed based on a systematic review of clinical studies related to CM dampness, registered trials, and semi-structured interviews with patients and healthcare professionals. Various stakeholders were invited to participate in a 2-round Delphi survey to scrutinize the important outcomes. A consensus meeting was held to determine the final COS-CMDS. RESULTS:We identified 1904 studies and 73 registered trials in the systematic review. Six patients and seven healthcare professionals were invited to participate in a semi-structured interview. Then, 541 outcomes were extracted, of which 397 were physicochemical. After combining certain outcomes (especially the physicochemical outcomes) and excluding those with weak relevance by discussion, 26 outcomes were included in round 1 of the Delphi survey. Round 1 was completed by 82.89% of participants, and 22 outcomes were carried on to round 2. Round 2 was completed by 92.06% of participants, and 14 outcomes achieved consensus for inclusion in the COS. Nineteen stakeholders attended the consensus meeting, voted, and discussed the final COS. It included evaluation of dampness syndrome, CM syndrome assessment, effective response, validated laboratory outcomes of CM dampness syndrome, and adverse events. CONCLUSION:The COS-CMDS provides a reference for the selection and reporting of outcomes in clinical research concerning CM dampness syndrome, embodying the characteristics of CM. Please cite this article as: Qiu XY, Tang Q, Cheng T, Cao WC, Liu BQ, Wen ZH, Li G. Developing a core outcome set for clinical research on Chinese medicine dampness syndrome. J Integr Med. 2026; 24(2):201-209.
OBJECTIVE:This study aimed to identify the optimal frequency of acupuncture for alleviating inflammatory pain and to explore the specific mechanisms through which it regulated microglial polarization. METHODS:We first measured the frequency and angle of acupuncture manipulation using an acupuncture manipulation parameter sensor. An inflammatory pain model was induced in Sprague-Dawley rats via injection of complete Freund's adjuvant (CFA) to the hind paw. Using the previously developed acupuncture manipulation simulator, we delivered precisely controlled stimulation with three frequencies (1, 2 and 4 Hz) to the Zusanli (ST36) acupoint. The optimal frequency for relieving inflammatory pain was determined by assessing paw withdrawal threshold, withdrawal latency and oedema. The autophagy inhibitor 3-methyladenine (3-MA) and α7 nicotinic acetylcholine receptor (α7nAChR) antagonist methyllycaconitine (MLA) were intrathecally injected to inhibit microglial autophagy and α7nAChR activation, respectively. Western blotting was used to measure autophagy-related protein levels. Spinal microglial polarization was evaluated using immunofluorescence analysis. The levels of pro- and anti-inflammatory cytokines were measured using enzyme-linked immunosorbent assay. The changes of mitochondrial morphology of spinal microglia were observed with transmission electron microscopy. RESULTS:The acupuncture manipulation simulator was used to precisely deliver treatments to CFA rats at three different frequencies with a rotation of 180°. Acupuncture manipulation at all three frequencies can effectively alleviate inflammatory pain and promote M2 polarization of the microglia, with 4 Hz acupuncture producing the best analgesic effect. The administration of 3-MA inhibited autophagy in spinal microglia, thereby reversing both the analgesic effect of acupuncture and its modulatory effect on microglial polarization. MLA markedly downregulated α7nAChR expression, inhibited autophagy, promoted M1 microglial polarization, and attenuated the analgesic effects of acupuncture. Moreover, acupuncture significantly decreased the expression of acetylcholinesterase. CONCLUSION:Frequency of needle stimulation may be a critical factor influencing the analgesic efficacy of acupuncture. Acupuncture may mitigate inflammatory pain by promoting microglial polarization through α7nAChR-mediated autophagy. Please cite this article as: Dong GQ, Gao H, Sun YJ, Yang QH, Yao Y, Yang HY. Acupuncture alleviates inflammatory pain by regulating microglial polarization through α7nAchR-mediated autophagy. J Integr Med. 2026; 24(3):429-442.
The integration of traditional Chinese medicine (TCM) and Western medicine has shaped clinical practice in China for decades, largely through pragmatic collaboration, combining distinct diagnostic and therapeutic modalities to optimize patient care. With advances in data science, systems biology and artificial intelligence, a new phase of integration is emerging. These technologies are enabling a shift from viewing TCM through the lens of modern clinical medicine to recognizing that TCM's holistic perspective is a driver for future medical innovation. We outline a framework for future medicine, an integration of medical paradigms that is built around a new system of classification, combination therapeutics, and molecular dynamics. Please cite this article as: Ji G, Zhang C, Lü AP. The integration of Chinese and Western medicines: Shaping the future of medical science. J Integr Med. 2026; 24(1):3-6.
OBJECTIVE:This study used machine learning methods to develop a model that can offer personalized acupoint prescriptions for patients based on their symptoms, enhancing both the efficiency and effectiveness of acupuncture and moxibustion therapy (AMT). METHODS:We first preprocessed textual AMT data to build an acupoint prescription database designed for machine learning applications. Then, based on data analysis, we selected the hierarchical classification model hierarchical attention-based recurrent neural network (HARNN) to determine acupoint prescriptions based on symptoms. Computational experiments were conducted using 5-fold cross-validation to evaluate the model's performance, with intersection over union (IoU) as the primary evaluation metric. Finally, to enhance model interpretability, the local interpretable model-agnostic explanation (LIME) method was applied to visualize prediction results and improve its clinical applicability. RESULTS:On the original dataset of 5000 samples, HARNN achieved an IoU of 0.883 in predicting acupoint prescriptions. After data augmentation, the IoU reached 0.954 in 5-fold cross-validation, and 0.932 on a test set of 1000 original samples. The use of LIME enabled intuitive visualization of the model's prediction rationale, thereby enhancing the model's reliability. CONCLUSION:This study developed a hierarchical and interpretable machine learning model that predicts acupoint prescriptions based on symptoms, integrating HARNN for hierarchical classification and LIME for interpretability, which provides an effective technical approach and methodology for the intellectualization of AMT. Please cite this article as: Yang H, Wu R, Nakata M, Ge QW. A hierarchical and interpretable machine learning model for acupoint determination. J Integr Med. 2026; 24(3):340-351.
OBJECTIVE:Progressive ground-glass nodules (GGNs) are associated with a risk of malignancy. Early identification and intervention are crucial for lung cancer prevention. Traditional Chinese medicine (TCM) has advantages of syndrome differentiation, holistic adjustment, and whole-process management. In this study, we built a risk assessment model based on the integration of TCM symptoms and imaging features to identify risks of GGN progression and to guide personalized TCM management and treatment. METHODS:This study enrolled 864 patients with GGNs from January 2015 to December 2023. Assessment factors included general demographic information, TCM symptoms, and imaging features. Machine learning algorithms were used to screen risk factors, regression models were used to establish GGN progression risk assessment models, and a nomogram was used to assess the risk of progression. RESULTS:Age, second-hand smoke exposure, acid reflux, breast or abdominal pain, chest tightness, depression, heartburn, tongue with little coating, and the diameter of the largest pulmonary nodule were significant risk factors for GGN progression. In the nomogram model, the TCM symptom of acid reflux made the highest contribution. The constructed model using these key factors was used to assess the risk of GGN progression. The receiver operating characteristic curve showed that the area under the curve (AUC) in the training set was 0.70 (95% confidence interval [0.65, 0.75]), and the AUC in the test set was 0.74 (95% confidence interval [0.65, 0.82]). CONCLUSION:This study was the first to establish a GGN progression risk assessment model using TCM clinical symptoms and imaging features. The model can help individuals and doctors better understand the health status and take timely preventive measures. Please cite this article as: Maolan A, Yu LH, Li Y, Yan ZS, Xiang XH, Wang LF, Guo QJ, Hu JQ, Zhang GH, Ren XL, Li J, Sun TH, Yang W, Liu R, Hua BJ. A progression risk assessment model for pulmonary ground-glass nodules based on traditional Chinese medicine clinical symptoms combined with imaging. J Integr Med. 2026; 24(3):376-386.
OBJECTIVE:Non-small cell lung cancer (NSCLC), a leading cause of cancer-related mortality, presents a poor prognosis due to its tendency to metastasize and its resistance to standard therapies. Montanine (MTN), a naturally occurring alkaloid, has recently shown potential as an anticancer agent. However, the specific mechanisms through which it exerts its anticancer effects are still largely unknown. This study investigates the anti-NSCLC potential of MTN by utilizing integrative network pharmacology alongside in vitro and in vivo experimental validations. METHODS:Genes targeted by MTN in NSCLC were identified and subjected to functional enrichment analysis to elucidate the most enriched signaling pathways. A protein-protein interaction network was constructed to identify the interactions of potential targets. Adrenoceptor β2 (ADRB2) expression in lung cancer was analyzed using data from The Cancer Genome Atlas and Gene Expression Omnibus datasets. The effects of MTN on NSCLC cell lines, including migration, proliferation, viability and apoptosis, were assessed in vitro. MTN-related mechanisms were investigated using quantitative reverse transcription-polymerase chain reaction and Western blotting. Furthermore, an in vivo lung cancer metastasis experiment was performed in rats using a tail vein assay. RESULTS:MTN at nontoxic doses significantly reduced cell migration and lung colonization in an in vivo metastasis study (P < 0.05). Network pharmacology revealed 29 targets of MTN in NSCLC, highlighting ADRB2 as a primary target linked to poor prognosis in lung cancer. In vitro studies confirmed that MTN notably upregulated ADRB2 expression and downregulated epithelial-mesenchymal transition (EMT) signaling pathways, which was further enhanced by terbutaline sulfate, an ADRB2 activator. CONCLUSION:MTN is a promising therapeutic agent for NSCLC by suppressing the migration via ADRB2 and EMT mechanisms. Please cite this article as: Iksen I, Singharajkomron N, Wongtayan A, Wattanathamsan O, Choonhapan A, Wademonkolgorn S, Nguyen HM, Hoang THX, Nguyen HT, Pongrakhananon V. Unveiling the antimetastatic activity and molecular mechanism of montanine in lung cancer cells via the integration of network pharmacology approaches with in vitro and in vivo investigations. J Integr Med. 2026; 24(2):253-264.
OBJECTIVE:This study investigated the effects of distinct electroacupuncture (EA) intensities in alleviating mechanical hypersensitivity by attenuating spinal dorsal horn (SDH) neuronal sensitization in inflammatory muscle pain. METHODS:Male Sprague-Dawley rats received an intra-muscular injection of complete Freund's adjuvant (CFA) in the left gastrocnemius muscle to induce inflammatory muscle pain. EA with distinct intensities activating Aβ-, Aδ- and C-fibers (EAAβ, EAAδ and EAC) was applied after CFA injection. Pain behaviors were evaluated by weight-bearing asymmetry, the Randall-Selitto test, and the von Frey test. Spinal neuronal activities were observed by in vivo extracellular recordings with a microelectrode array. Neuronal sensitization was assessed through wind-up phenomenon of wide dynamic range (WDR) neurons and long-term potentiation (LTP) of spinal C-fiber-evoked field potential (CFEFP). RESULTS:Both EAAδ and EAC significantly alleviated CFA-induced hyperalgesia. Moreover, EAAδ and EAC interventions markedly reduced the activity of WDR neurons in response to stimulation. Importantly, the wind-up phenomenon of WDR neurons evoked by repetitive noxious stimuli was both immediately and sustainably reduced after EA intervention, with EAC showing a more pronounced effect. Furthermore, EAAδ and EAC increased the threshold of the spinal CFEFP, while EAC intervention additionally significantly attenuated the occurrence of LTP. CONCLUSION:Suppressing the SDH neuronal sensitization by activating Aδ- and C-fiber inputs may be the potential mechanism by which EA alleviates hyperalgesia in inflammatory muscle pain. Please cite this article as: Yu QQ, Sun XY, Chen JK, Li M, Wang XY, Su YS, Zhang ZY, Jing XH. Distinct intensity of electroacupuncture ameliorates mechanical hypersensitivity by attenuating neuronal sensitization in spinal dorsal horn in a rat model of inflammatory muscle pain. J Integr Med. 2026; 24(3):443-453.
BACKGROUND:Endometriosis is an estrogen-dependent, progesterone-resistant gynecological disorder, with dysmenorrhea being the most common manifestation. OBJECTIVE:This study evaluates the efficacy and safety of the Tibetan herbal medication Honghua Ruyi Pill (HHRY) in managing endometriosis-related dysmenorrhea. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:This is a multi-center, randomized, placebo-controlled, double-blinded clinical trial conducted in seven hospitals in China from July 2021 to January 2023. A total of 164 patients with endometriosis and moderate or severe dysmenorrhea (visual analog scale [VAS] score ≥ 4) were assigned to the treatment or placebo group in a 1:1 ratio by block randomization. Patients received HHRY or placebo twice a day for three consecutive menstrual cycles (MCs) and were followed up for three MCs after stopping the medication. MAIN OUTCOME MEASURES:Primary outcomes were VAS score of the maximum (VASmax) of dysmenorrhea, endometriosis health profile-5 (EHP-5) score, and 5-level EuroQoL 5-dimension version (EQ-5D-5L) score. Secondary outcomes were VASmax of non-menstrual pelvic pain, days of leave taken, emergent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and changes in uterine, cyst and nodule sizes. Safety profiles were assessed based on adverse events, vital signs, serology markers, urinalysis, and liver and kidney function indicators. RESULTS:VASmax of dysmenorrhea, EHP-5 score, EQ-5D-5 L score, and VASmax of non-menstrual pelvic pain were significantly lower in the HHRY group compared to the placebo group at the final follow-up (3.00 vs 5.50, P < 0.001; 4.00 vs 8.00, P < 0.001; 4.00 vs 9.00, P < 0.001; 0.00 vs 1.00, P < 0.001; respectively). The emergent use of NSAIDs for breakthrough pain showed no significant difference between groups (P > 0.999), but the number of patients who had taken time off was significantly different (5.00 vs 14.00, P = 0.028). Sonographic evaluations indicated no significant change in uterine size (P = 0.183) but showed a significant reduction in cyst size (2.09 cm vs 0.20 cm, P = 0.027, sum of 3 diameters of cysts) and nodule size (0.70 cm vs 0.00 cm, P < 0.001, maximum nodule diameter). Safety analysis showed no significant difference in the incidence of adverse events between groups (18.85% vs 28.05%, P = 0.059). CONCLUSION:HHRY can improve dysmenorrhea, chronic pelvic pain, and quality of life in patients with endometriosis. It has a good overall safety profile, and a 3-month treatment can maintain its effects for at least 3 months after the last dose. HHRY may be considered as a new therapeutic option for treating endometriosis-related dysmenorrhea. TRIAL REGISTRATION:Trial registration at ClinicalTrials.gov with registration number: NCT04942015. Please cite this article as: Han M, Liang XF, Gao J, Wang Y, Cao LX, Wang BJ, Wang Y, Zerang Z, Liu JP, Du HL. Honghua Ruyi Pill, a compound herbal medicine, improves endometriosis-related dysmenorrhea: A multicenter randomized, double-blind, placebo-controlled trial. J Integr Med. 2026; 24(2):182-191.
OBJECTIVE:Enhancing innate immunity through interferons (IFNs) and IFN-stimulated genes (ISGs) offers a promising strategy for preventing herpes simplex virus type 1 (HSV-1) infection. Prunella vulgaris L., a medicinal herb, has demonstrated significant anti-HSV activity; in particular, its derived polysaccharide complex (PVE30) effectively inhibits viral replication. In this study, we investigate whether PVE30 exerts an anti-HSV-1 activity through activation of the innate immune response. METHODS:To determine the primary stage at which PVE30 exerts its effects during the HSV-1 life cycle, plaque reduction assays were conducted. Viral infection was further assessed by investigating the DNA copies, mRNA levels and protein expression of HSV-1 in infected cells using real-time polymerase chain reaction (RT-PCR) and Western blotting. The activation of the innate immune response was evaluated by detecting mRNA levels of ISGs, including MX dynamin-like GTPase 1 (Mx1), Mx2, 2'-5'-oligoadenylate synthetase 1 (OAS1), ISG15 and IFN regulatory factor 7 (IRF7) using RT-PCR, and levels of TANK-binding kinase 1 (TBK1) and IRF3 proteins using Western blotting. The translocation of phosphorylated IRF3 and stimulator of IFN genes (STING) was observed through fluorescence microscopy. RESULTS:PVE30 pre-treatment exerted protective effects against HSV-1 infection in human immortalized keratinocytes by enhancing the innate immune response. This was shown by increased transcriptional levels of IFN-β and antiviral ISGs, along with a significant reduction in HSV-1 DNA copies, mRNA expression and protein levels. Mechanistically, PVE30 promoted TBK1 phosphorylation, leading to nuclear translocation of IRF3 and subsequent IFN-β transcription; these effects were diminished by TBK1 inhibitor GSK8612. Additionally, STING was identified as a key mediator in PVE30-activated TBK1 signaling, as its inhibition induced by C-176 reduced PVE30's efficacy. CONCLUSION:This study elucidated the molecular mechanisms underlying the protective effects of PVE30 against HSV-1 infection. PVE30 exerted its protective role by enhancing STING-TBK1-IRF3 pathway-mediated innate immune response. Please cite this article as: Zhang YB, Xu L, Yuan M, Liu MF, Li Y, Zhong XL, Lin ZX, Xian YF, Lu P, Xi ZC, Xu HX. Protective effects of Prunella vulgaris polysaccharides against herpes simplex virus type 1 infection through the STING-TBK1-IRF3 pathway. J Integr Med. 2026; 24(3):454-465.
Background: Auriculotherapy is a simple, convenient, nonpharmacological option that has shown positive effects for insomnia patients, but its efficacy and safety remain unknown. Objective: The aim of this study is to evaluate the efficacy and safety of auricular therapy for insomnia. Design, setting, participants and intervention: An 18-week (2-week screening, 4-week treatment, and 12-week follow-up), recruiter- and assessor-blinded, randomized, sham-controlled trial was performed. Patients were recruited from outpatient settings at three clinical centers in China from 2 February 2023 to 26 January 2024. Participants had insomnia for more than 3 months and met the criteria classified in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patients were randomly assigned in a 1:1 ratio to receive auricular therapy (AT) or sham AT (SAT) for 4 consecutive weeks, twice a week, and once every 3 days. Main outcome measures: Primary outcome was the response rate at week 4 after treatment, defined as the percentage of patients with at least a 50% reduction in Pittsburgh Sleep Quality Index (PSQI) from baseline. Secondary outcomes consisted of response rates at other time points, PSQI and 4 related scales, actigraphy-recorded sleep efficiency, sleep arousal frequency, and total sleep time. Results: A total of 234 participants were screened, and 156 patients (122 female [78.2%]; mean [standard deviation] age, 37.2 [13.5] years) were included in the intention-to-treat analysis, with 78 participants randomized to each group. A total of 117 participants (75%) were followed up for 3 months. The AT group had a higher response rate at week 4 than the SAT group (39.73% [29/73] vs 23.29% [17/73], P = 0.03), and the response rates for the AT and SAT groups at week 2 were 28.38% (21/74) and 13.33% (10/75), respectively (P = 0.02). The differences between the two groups in the PSQI at each time point (P < 0.05) and the Insomnia Severity Index at weeks 4 and 12 (both P = 0.03) were also statistically significant. The other partial outcomes also showed statistically significant differences. Adverse events occurred in 2 cases in the AT group (2.60%). Conclusion: Four-week AT treatment was an effective and safe alternative therapy for insomnia, although the difference with the SAT treatment did not reach the minimal clinically important difference. Adverse events were mild or transient.
