ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

Triclosan (TCS) and triclocarban (TCC) are widely used synthetic broad-spectrum antibacterial agents that can enter the human body through the skin, gastrointestinal tract, and other pathways. More and more studies have found that exposure to TCS and TCC can affect human health, but currently, review reports on the health effects of human exposure to TCS and TCC are limited. Therefore, this study reviewed population studies on the relationship between TCS and TCC exposure and health effects by searching the PubMed database, summarized the associated health outcomes, and elucidated the biological mechanisms. A total of 56 studies were retrieved, among which cross-sectional studies (25 studies, 44.64%) and cohort studies (25 studies, 44.64%) accounted for a relatively large proportion, while case-control studies (6 studies, 10.72%) were relatively few. Studies on TCS exposure (48 studies, 85.71%) were far more prevalent than those on TCC exposure (2 studies, 3.57%). The remaining 6 studies involved both TCS and TCC exposure. The research results revealed that TCS exposure was associated with male and female abnormal reproductive functions, fetal growth restriction, abnormal behavior development in children, obesity, gestational diabetes mellitus (GDM), and immune-related diseases. Although the results of different studies show significant differences, they have indicated that exposure to TCS is a potential risk factor for these health problems. Due to the limited number of studies, the evidence for the relationship between TCC exposure and most of the aforementioned health effects is insufficient. Population studies and in vitro and in vivo studies have shown that exposure to TCS and TCC can interfere with the microbial homeostasis, the endocrine system, oxidative stress and immune function of the body, which are potential mechanisms causing adverse health effects. In the future, large-scale prospective cohort studies, as well as in vivo and in vitro studies, are still needed to further clarify the associations between TCS and TCC exposure and health effects, and to deeply explore its mechanism of action. These efforts will provide references for clarifying the human health hazards of TCS and TCC exposure and formulating targeted prevention and control strategies.

The disease-syndrome combination model of spleen deficiency with dampness pattern in ulcerative colitis（SDDP-UC） is an important experimental carrier for traditional Chinese medicine （TCM） research on the prevention and treatment of ulcerative colitis （UC）， and the quality of model construction and evaluation directly influences the scientific rigor and translational value of related research conclusions. However， this field still lacks methodological synthesis and a standardized consensus. Based on a comprehensive review of existing literature， this paper summarized isomorphic cues between the spleen deficiency with dampness pattern and UC across four dimensions， including energy metabolism， immune homeostasis， mucosal barrier， and intestinal microecology. The cues were mainly involved in impaired mitochondrial energy supply and glucose metabolic reprogramming， a lowered pro-inflammatory threshold of innate immunity with insufficient adaptive immune regulation， disruption of epithelial barrier gating accompanied by compromised repair capacity， and attenuation of the luminal hypoxia barrier with accumulation of toxic metabolites. A mutually reinforcing process between local "form damage" and systemic "Qi depletion" was further interpreted from a holistic perspective. Regarding modeling strategies， existing studies predominantly use rats as the carrier， apply combined interventions such as improper diet， external damp exposure， and fatigue-related dysregulation to establish the spleen deficiency with dampness pattern background， and subsequently superimpose chemical stimulation to induce UC-like colonic damage， with a total modeling period generally spanning three to four weeks. In terms of the evaluation system， a multidimensional framework integrating syndrome assessment， histopathology， mechanistic indices， and pharmacodynamic counter-verification was outlined. On this basis， current methodological bottlenecks of models were systematically identified， including syndrome drift risk and compounded stress dilemma in temporal sequencing， syndrome confounding from etiological simulation， cross-sectional evaluation bias related to modeling duration， inadequate disease-syndrome linkage and control design within the evaluation system， and limited controls with overly single-track decision logic in formula-based syndrome verification. To address the above issues， a construction and evaluation strategy emphasizing streamlining of core etiological factors， multi-node dynamic monitoring， integration of core disease-syndrome indicator clusters， and establishment of a formula-based syndrome verification system was proposed， providing a reference for the standardized construction and scientific evaluation of the SDDP-UC model.

Periodontitis and diabetes have a close bidirectional relationship that is mutually exacerbated through mechanisms including inflammatory factor interplay and metabolic dysregulation. Research has shown that non-surgical periodontal therapy (NSPT), focused on scaling and root planing (SRP), effectively treats periodontitis, enhances glycemic control, and ameliorates systemic inflammation in diabetic patients. This review summarizes the glycemic improvement effects of diverse NSPT modalities (including SRP alone, SRP with adjunctive antimicrobials, and SRP with laser therapy) on patients with diabetes and periodontitis. SRP significantly reduces hemoglobin A1c (HbA1c) levels, while adjunctive antimicrobials and laser therapy considerably potentiate the glucose-lowering efficacy of SRP. Furthermore, we focus on elucidating the underlying regulatory mechanisms for NSPT-mediated glycemic control improvement, encompassing inflammation factor-mediated JNK/IKKβ pathway activation inducing insulin resistance; advanced glycation end products (AGEs)-triggered RAGE-ROS/NF-κB pathway dysregulation leading to pancreatic β-cell dysfunction; gut microbiota dysbiosis-driven TLR4-MyD88/TRIF signaling axis causing insulin resistance; flagellin from periodontal pathogens impairing insulin secretion; and lipopolysaccharide (LPS) of periodontal pathogens disrupting Th17/Treg balance with downstream STAT3/SOCS3 pathway inhibiting insulin signaling. These insights aim to provide novel references for targeted interventions and synergistic management of diabetes with periodontitis. Although current studies reveal potential benefits and partial mechanisms of NSPT, the following problems remain: unelucidated specific effector molecules and pathway networks for glycemic regulation by different NSPT regimens, significant interindividual variability in treatment response, and undetermined long-term stability of adjunctive therapy benefits. Future research should explore combined therapeutic strategies for synergistic efficacy, mechanistically dissect regulatory pathways, identify key targets, and advance precision management of diabetes-periodontitis comorbidities.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

The development of novel point-to-point drugs targeting resistance mechanisms is a critical and popular research field; nevertheless, success remains challenging. Therefore, given the short survival time and heightened expectations of patients with advanced NSCLC, the design of various combination therapy strategies––integrating preclinical, clinical, and real-world evidence (such as radiotherapy, chemotherapy, targeted therapy, antibody–drug conjugates, oncolytic viruses, and cell therapy)––may be a wise and practical choice to address the disease. Resistance to immunotherapy involves almost all cell types in the body, primarily cancer cells and T cells involved in immune surveillance. As a result of space limitations, this article focuses on the progress and challenges of various combined strategies for directly eliminating cancer cells. We also emphasize the realignment of treatment goals, shifting from primarily focusing on eliminating cancer cells (via chemotherapy and radiotherapy) to fully utilizing immune regulation to overcome resistance to immune checkpoint inhibitors.

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.