OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.

Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

The number of patients with vascular cognitive impairment(VC I)is increasing year by year,and its incidence rate is second only to that of Alzheimer's disease(AD),becoming the second leading cause of dementia.It should be noted that,VCI is a disease that can be controlled by early diagnosis and timely treatment,and It is even a disease that can achieve clinical cure.Therefore,an in-depth exploration of the pathogenesis of VCI,as well as the development of effective early diagnostic and preventive strategies,is not only of significant clinical guidance importance but also holds profound social value.The Klotho gene,an anti-aging gene,is primarily expressed in the brain's choroid plexus and kidneys.The Klotho protein it encodes not only has anti-aging and longevity-extending functions but is also closely associated with cognitive function.Current research has revealed a strong connection between Klotho protein levels and vascular cognitive impairment induced by ischemic stroke,suggesting that Klotho protein could serve as an important biomarker for predicting vascular cognitive impairment after ischemic stroke.This article aims to comprehensively summarize the latest research progresses on the Klotho gene and its polymorphisms,as well as the Klotho protein and cognitive impairment following ischemic stroke,both domestically and internationally,in the hope of providing a solid theoretical foundation and reference for further research in this field.

Objective To investigate the differences in speech recognition in noise between patients with con-genital and acquired single-sided deafness.Methods Sixty-two patients with single-sided deafness were included in this study,which included 31 congenital single-sided deafness(CSSD)cases and 31 acquired single-sided deafness(ASSD)cases according to the onset of deafness.Thirty-one normal hearing(NH)subjects were also included in this study as the control group.The ability of speech recognition in noise were tested and compared among the three groups,meanwhile the differences between patients with left and right single-sided deafness were compared.Results The speech recognition threshold in noise of ASSD patients was significantly higher than that of CSSD patients,and both of them were significantly higher than that of the NH subjects.Under the 0 and-2 dB signal-to-noise ra-tio conditions,the speech recognition score was significantly lower in ASSD patients compared to CSSD patients,but only in ASSD patients it was significantly lower than that of the NH group,with no significant difference be-tween CSSD patients and the NH group.A significant difference in speech recognition thresholds was observed be-tween left and right CSSD patients.Conclusion CSSD have better speech recognition in noise than ASSD patients,suggesting better central function compensation.In addition,the side of deafness affects the speech recognition per-formance of CSSD patients.

The chemical constituents of sesquiterpenes from 95% ethanol extract of Aquilariae Lignum Resinatum were isolated and purified by various column chromatography techniques, including silica gel, Sephadex LH-20, octadecylsilyl(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their planar structures and absolute configurations were elucidated by ultraviolet(UV) spectrometry, infrared(IR) spectroscopy, mass spectrometry(MS), nuclear magnetic resonance(NMR), electronic circular dichroism(ECD), and other techniques. Eight sesquiterpenoids were isolated and identified as(+)-(7R,10R)-selina-4,11-dien-12-dimethoxy-15-al(1),(+)-(7R,10R)-selina-4,11-diene-12,15-dial(2), agalleudesmanol B(3), aquisinenoid C(4), 12,15-dioxo-α-selinen(5), agarospiranic aldehyde B(6), neopetasane(7), and eremophila-7(11),9-dien-8-one(8). Compound 1 was a new compound, and it was the first time to find a dimethoxy substitution on the side chain of eudesmane-type sesquiterpene skeleton.
Sesquiterpenes/isolation & purification* ; Thymelaeaceae/chemistry* ; Molecular Structure ; Drugs, Chinese Herbal/isolation & purification* ; Magnetic Resonance Spectroscopy

Thyroid nodules are a common endocrine disorder, and their early detection and accurate diagnosis are crucial for the prevention of thyroid cancer. However, the highly heterogeneous morphology and boundaries of thyroid nodules pose significant challenges to their precise identification and classification. Traditional diagnostic approaches rely heavily on physicians' experience, which increases the risk of misdiagnosis and missed diagnoses. With the rapid advancement of computer-aided diagnosis (CAD) technologies, applying deep learning algorithms to the analysis of thyroid nodule ultrasound images has shown great potential. This paper reviews the latest research progress on deep learning-based CAD methods for thyroid nodules, with a focus on their applications in image preprocessing, segmentation and classification. The advantages and limitations of current techniques are analyzed, and potential future directions are discussed. This review aims to highlight the potential of deep learning in thyroid nodule diagnosis and to provide a foundation for selecting feasible pathways for future clinical applications.
Humans ; Thyroid Nodule/diagnostic imaging* ; Deep Learning ; Ultrasonography/methods* ; Diagnosis, Computer-Assisted/methods* ; Algorithms ; Thyroid Neoplasms/diagnostic imaging* ; Image Processing, Computer-Assisted/methods*