ObjectiveTo evaluate the clinical efficacy of Shenqi Yangxin decoction in the treatment of ischemic cardiomyopathy （ICM） with Qi and Yin deficiency and blood stasis syndrome and its effect on serum hydrogen sulfide （H₂S） and calcium ion （Ca²⁺）. MethodsA total of 64 ICM patients with Qi and Yin deficiency and blood stasis syndrome who met the inclusion criteria were randomly divided into a control group （n=32） and a treatment group （n=32）. All patients received conventional Western medicine treatment. The treatment group was additionally given Shenqi Yangxin decoction. The TCM syndrome score， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， 6-minute walk test （6MWT）， New York Heart Association （NYHA） cardiac function classification， and serum H₂S and Ca²⁺ levels were compared between the two groups pre- and post-treatment. ResultsTwo cases dropped out from each group during the study. Finally， 30 patients in each group were included in the analysis. There were no significant differences in age， gender， course of coronary heart disease， underlying diseases， and laboratory tests between the two groups. Compared with baseline， the TCM syndrome score， MLHFQ score， and NT-proBNP in both treatment group and control group decreased significantly （P<0.01）， LVEF， 6MWT， and H₂S increased significantly （P<0.01）， and serum Ca²⁺ increased （P<0.05）. Compared with the control group after treatment， the MLHFQ score and NT-proBNP in the treatment group decreased （P<0.05）， the TCM syndrome score decreased significantly （P<0.01）， LVEF， 6MWT， and serum Ca²⁺ increased （P<0.05）， and H₂S increased significantly （P<0.01）. The improvement degree of the NYHA cardiac function classification in the treatment group was higher than that in the control group， but there was no significant difference. ConclusionShenqi Yangxin decoction is effective in treating ICM patients with Qi and Yin deficiency and blood stasis， which could significantly improve cardiac function and quality of life， and its therapeutic effect may be related to the regulation of serum H₂S and Ca²⁺ levels.

Accommodative dysfunction, particularly accommodative lag, acts as a core hub connecting near work activity to myopic axial elongation. This review thoroughly explores the multidimensional biological mechanisms by which accommodative function drives axial growth. In addition to the classic pathway where hyperopic defocus signals induce retinal-choroidal-scleral biochemical remodeling, two other mechanisms are highlighted: a biomechanical pathway involving direct mechanical traction on the equatorial sclera caused by sustained ciliary muscle contraction, and a neural pathway where abnormal accommodative micro fluctuations degrade retinal image quality, thereby triggering abnormal ocular growth. Based on these comprehensive mechanisms, this paper systematically analyzes the principles of pharmacological(atropine), optical(orthokeratology, defocus lenses), and vision therapy interventions. Myopia progression results from the integrated regulation of optical defocus, mechanical stress, and neural dynamics. Future myopia control should advance toward precise, personalized combination strategies tailored to individual accommodative and genetic profiles.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

ObjectiveTo enhance the genetic diagnostic yield for fetal short femur length （FL） and to evaluate the integration of whole exome sequencing （WES） with chromosomal abnormality detection in prenatal diagnosis. MethodsA total of 27 mid-to-late trimester fetuses diagnosed with short FL ［FL < 5th percentile for gestational age or < -2 SD （Standard Deviation）］ at the Prenatal Diagnosis And Medical Genetics Center，Shenshan Medical Center，Memorial Hospital of Sun Yat-Sen University between November 2023 and May 2025 were included. Amniotic fluid or umbilical cord blood samples were collected and subjected to chromosomal karyotyping （19cases）， chromosomal microarray analysis （CMA） or low-coverage whole genome copy number variation（CNV-Seq） （27 cases）， and trio-based whole exome sequencing （trio-WES） （27 cases）. The pathogenicity of genetic variants were interpreted according to the American College of Medical Genetics and Genomics （ACMG） guidelines. ResultsTwenty-six genomic variants were detected in 17 of the 26 fetuses， including numerical chromosomal abnormalities （mosaic type）， copy number variations （CNVs）， single nucleotide variants （SNVs） and insertions-deletions （INDELs）. Genomic variants detected in 11 cases could explain the short femur phenotype.The overall diagnostic rate was 11/27， with pathogenic/likely pathogenic variants explaining 9 cases and variants of uncertain significance （VUS） accounting for 1 cases. In addition Chromosomal karyotype analysis revealed chromosome mosaicism explaining 1 case. The diagnostic rate of CNV detection （CMA/CNV-seq） was 2/27， while WES achieved a diagnostic rate of 10/27， with an incremental yield of 8/27 in cases with negative or inconclusive CNV results. Pathogenic mutations involved genes such as FGFR3， SHOX， DUOX2， CLCN5， and HBA1/HBA2. ConclusionTrio-WES significantly improves the genetic diagnostic rate for fetal short femur length， particularly in cases where chromosomal analysis fails to identify a cause. Karyotyping remains valuable for detecting low-level mosaicism in large-scale chromosomal abnormalities， thereby complementing WES and CNV detection. A stepwise or parallel genetic testing strategy is recommended in prenatal diagnosis to optimize diagnostic efficiency and support clinical decision-making.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

BACKGROUND: There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region. OBJECTIVE: This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis. MAIN OUTCOME MEASURES: The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention. RESULTS: Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively. CONCLUSION: Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions. TRIAL REGISTRATION ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult ; Female ; Humans ; Male ; Young Adult ; Acupuncture Points ; Acupuncture Therapy ; Body Temperature ; Healthy Volunteers ; Lumbosacral Region/physiology* ; Moxibustion ; Adolescent

Aconiti Lateralis Radix Praeparata (Fuzi) represents a significant traditional Chinese medicine (TCM) that exhibits both notable pharmacological effects and toxicity. Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components, primarily diterpenoid alkaloids. To comprehensively analyze the chemical variations between different Fuzi products, ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was employed to systematically characterize Shengfuzi, Heishunpian and Baifupian. A total of 249 diterpenoid alkaloids present in Shengfuzi were identified, while only 111 and 61 in Heishunpian and Baifupian were detected respectively, indicating substantial differences among these products. An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers. Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples, 8 robust markers distinguishing these products were identified, including AC1-propanoic acid-3OH, HE-glucoside, HE-hydroxyvaleric acid-2OH, dihydrosphingosine, N-dodecoxycarbonylvaline and three unknown compounds. Additionally, the MS imaging (MSI) technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi, revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian. The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products. This research provides valuable insights into the material basis for future investigations of different Fuzi products.
Diterpenes/chemistry* ; Alkaloids/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Aconitum/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Mass Spectrometry/methods* ; Plant Roots/chemistry* ; Molecular Structure