ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease （DKD） in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis， and to explore its mechanism of inhibiting the endoplasmic reticulum stress （ERS）-apoptosis axis and delaying renal fibrosis （RF）. MethodsA single-center， randomized， parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine （TCM） pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group （conventional Western medicine treatment） and an experimental group （Yishen Jiangtang decoction combined with conventional Western medicine treatment）， with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters： Blood urea nitrogen （BUN）， serum creatinine （SCr）， estimated glomerular filtration rate （eGFR）， urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C）. Enzyme-linked immunosorbent assay （ELISA） kits were used to measure serum glucose-regulated protein 78 （GRP78）， serum cysteinyl aspartate-specific protease-3 （Caspase-3）， and serum and urinary transforming growth factor-β₁ （TGF-β₁） levels before and after treatment. TCM symptom scores， TCM syndrome efficacy， and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3， as well as serum and urinary levels of TGF-β1， with renal function， proteinuria， and glucose and lipid metabolism indicators in patients with DKD. In addition， safety indicators were also monitored. ResultsA total of 75 patients completed the study （38 in the control group and 37 in the experimental group）. ① Baseline data： The two groups were comparable in terms of sex and age， with no statistically significant difference. ② Efficacy outcomes： Compared with baseline levels， both groups showed reductions in BUN， SCr， UACR， FBG， TG， TC， LDL-C， and TCM symptom scores （P<0.01） and increases in eGFR level （P<0.01）. Moreover， the experimental group outperformed the control group in altering the indicators above （P<0.05）. Regarding TCM syndrome efficacy， the total response rate in the experimental group was 83.78%， which was higher than that （57.89%） in the control group （P<0.05）. Regarding overall clinical efficacy， the total response rate in the experimental group was 78.38%， which was higher than that （50.00%） in the control group （P<0.05）. ③ Mechanism outcomes： Compared with baseline levels， both groups showed declined serum levels of GRP78， Caspase-3， and TGF-β₁ and urinary level of TGF-β₁ after treatment （P<0.01）. Moreover， the experimental group showed greater declines than the control group （P<0.05）. The serum levels of GRP78， Caspase-3，and TGF-β₁ and the urinary level of TGF-β₁ in DKD patients showed positive correlations with BUN， SCr， UACR， and FBG and negative correlations with eGFR （P<0.05）. ④ Safety outcomes： Neither group showed drug-related adverse reactions， and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms， correct glucose and lipid metabolism disorders， and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.

ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease （DKD） in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis， and to explore its mechanism of inhibiting the endoplasmic reticulum stress （ERS）-apoptosis axis and delaying renal fibrosis （RF）. MethodsA single-center， randomized， parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine （TCM） pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group （conventional Western medicine treatment） and an experimental group （Yishen Jiangtang decoction combined with conventional Western medicine treatment）， with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters： Blood urea nitrogen （BUN）， serum creatinine （SCr）， estimated glomerular filtration rate （eGFR）， urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C）. Enzyme-linked immunosorbent assay （ELISA） kits were used to measure serum glucose-regulated protein 78 （GRP78）， serum cysteinyl aspartate-specific protease-3 （Caspase-3）， and serum and urinary transforming growth factor-β₁ （TGF-β₁） levels before and after treatment. TCM symptom scores， TCM syndrome efficacy， and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3， as well as serum and urinary levels of TGF-β1， with renal function， proteinuria， and glucose and lipid metabolism indicators in patients with DKD. In addition， safety indicators were also monitored. ResultsA total of 75 patients completed the study （38 in the control group and 37 in the experimental group）. ① Baseline data： The two groups were comparable in terms of sex and age， with no statistically significant difference. ② Efficacy outcomes： Compared with baseline levels， both groups showed reductions in BUN， SCr， UACR， FBG， TG， TC， LDL-C， and TCM symptom scores （P<0.01） and increases in eGFR level （P<0.01）. Moreover， the experimental group outperformed the control group in altering the indicators above （P<0.05）. Regarding TCM syndrome efficacy， the total response rate in the experimental group was 83.78%， which was higher than that （57.89%） in the control group （P<0.05）. Regarding overall clinical efficacy， the total response rate in the experimental group was 78.38%， which was higher than that （50.00%） in the control group （P<0.05）. ③ Mechanism outcomes： Compared with baseline levels， both groups showed declined serum levels of GRP78， Caspase-3， and TGF-β₁ and urinary level of TGF-β₁ after treatment （P<0.01）. Moreover， the experimental group showed greater declines than the control group （P<0.05）. The serum levels of GRP78， Caspase-3，and TGF-β₁ and the urinary level of TGF-β₁ in DKD patients showed positive correlations with BUN， SCr， UACR， and FBG and negative correlations with eGFR （P<0.05）. ④ Safety outcomes： Neither group showed drug-related adverse reactions， and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms， correct glucose and lipid metabolism disorders， and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.

ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

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.

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.