ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is one of the most serious kinds of sperm defects, leading to asthenoteratozoospermia and male infertility. In this study, we use whole-exome sequencing to identify genetic factors that account for male infertility in a patient born from a consanguineous Pakistani couple. A homozygous frameshift mutation (c.1399_1402del; p.Gln468ArgfsTer2) in axonemal dynein light chain domain containing 1 ( AXDND1 ) was identified in the patient. Sanger sequencing data showed that the mutation was cosegregated recessively with male infertility in this family. Papanicolaou staining and scanning electron microscopy analysis of the sperm revealed severely abnormal flagellar morphology in the patient. Immunofluorescence and western blot showed undetectable AXDND1 expression in the sperm of the patient. Transmission electron microscopy analysis showed disorganized sperm axonemal structure in the patient, particularly missing the central pair of microtubules. Immunofluorescence staining showed the absence of sperm-associated antigen 6 (SPAG6) and dynein axonemal light intermediate chain 1 (DNALI1) signals in the sperm flagella of the patient. These findings indicate that AXDND1 is essential for the organization of flagellar axoneme and provide direct evidence that AXDND1 is a MMAF gene in humans, thus expanding the phenotypic spectrum of AXDND1 frameshift mutations.
Humans ; Male ; Sperm Tail/ultrastructure* ; Frameshift Mutation ; Infertility, Male/pathology* ; Pakistan ; Pedigree ; Consanguinity ; Axonemal Dyneins/genetics* ; Adult ; Spermatozoa ; Exome Sequencing

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Maintaining long-term stability of patient's condition is crucial in the treatment for bipolar disorder， while accurately assessing the patient's disease status is important and challenging in maintaining treatment. Excessive status expectation is common in patients with bipolar depression， which would warp the patient's perception of his or her own disease status and， thus， ultimately interfere with clinical decisions. Heightened vigilance should be given to such phenomenon. This paper explores the phenomenon and potential mechanisms of excessive status expectation in patients with bipolar disorder， providing ideas for related diagnosis， treatment and research. ［Funded by Jiangsu Provincial Science and Technology PProject （number， BE2015609）］