OBJECTIVES: To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula. METHODS: A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated. RESULTS: The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas. CONCLUSIONS The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans ; Male ; Female ; Child, Preschool ; Child ; Coronary Artery Disease/diagnostic imaging* ; Infant ; Mucocutaneous Lymph Node Syndrome ; Regression Analysis ; Coronary Vessels/diagnostic imaging* ; Echocardiography ; Adolescent

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Immunotherapy has become a pivotal treatment regimen for hepatocellular carcinoma (HCC); however, its efficacy is influenced by various factors. Hepatitis B virus (HBV) infection is one of the primary etiological factors leading to HCC. HBV DNA replication can alter the immune microenvironment through multiple mechanisms, notably by upregulating the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby facilitating tumor immune escape. Paradoxically, this upregulation of PD-1/PD-L1 may enhance the response rate to PD-1/PD-L1 inhibitors and potentiate the antitumor effect. This review aims to summarize current research progress on the relationship between HBV DNA load and the efficacy of PD-1/PD-L1 inhibitors, explore the underlying mechanisms, and provide a scientific basis for promoting personalized treatment strategies for patients with HBV-related HCC.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of post-stroke depression(PSD) and analyzed the clinical study characteristics and outcome indicators, aiming to optimize the design and establish the core outcome set in the future clinical trials of the TCM treatment of PSD. PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed were searched for the relevant RCT published in recent 3 years. The basic characteristics, intervention measures, and outcome indicators of the included RCT were extracted, and the descriptive analysis was carried out. A total of 76 RCTs were eventually included, with the sample size concentrated in 80-100 cases. The most frequent TCM syndromes were liver depression and Qi stagnation(15 times, 31.91%) and phlegm combined with stasis(5 times, 10.63%). The frequency of intervention methods followed a descending trend of TCM decoction(35 times, 46.05%) and TCM decoction + acupuncture(4 times, 5.26%), Chinese patent medicine(3 times, 3.94%), and the intervention mainly lasted for 1 to 3 months(43 times, 60.56%). The adverse reactions of patients were mainly digestive system reaction(150 patients, 39.37%) and nervous system reaction(112 patients, 29.39%). Most of the included studies had unclear risk of bias, involving 84 outcome indicators, which belonged to 8 indicator domains. The RCTs of TCM treatment of PSD showed a variety of problems, such as non-standard TCM syndrome differentiation, inconsistent names of TCM syndrome scores and measurement tools, low quality, unclear risk of bias, neglect of endpoint indicators, unreasonable selection of substitute indicators, lack of differentiation between primary and secondary outcome indicators, non-standard reporting of safety indicators, insufficient attention to economic indicators, and lack of long-term prognosis evaluation. It is suggested that the future research should improve the quality of methodology and build a standardized core outcome set to promote the development of high-quality clinical research in this field.
Humans ; Randomized Controlled Trials as Topic ; Drugs, Chinese Herbal/administration & dosage* ; Stroke/psychology* ; Depression/etiology* ; Treatment Outcome ; Medicine, Chinese Traditional