ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

ObjectiveGastric hemorrhage is one of the most common and life-threatening emergencies of the upper digestive tract. Early identification and continuous monitoring are essential for reducing rebleeding rates and mortality, particularly within the critical early hours after onset. Although endoscopy and radiological imaging can accurately localize bleeding sites, these approaches are invasive, resource-intensive, and unsuitable for continuous bedside monitoring. Electrical impedance tomography (EIT), as a noninvasive and radiation-free functional imaging technique, offers real-time visualization of conductivity distribution and has the potential for detecting intragastric bleeding based on the electrical contrast between blood and surrounding gastric tissues. In this study, a three-dimensional gastric EIT (3D-gEIT) framework is proposed to achieve noninvasive, real-time, and dynamic monitoring of gastric hemorrhage, with emphasis on spatial localization and quantitative volume assessment. MethodsA three-dimensional upper-abdominal simulation model incorporating the stomach, gastric wall, gastric contents, and surrounding tissues was established. Three electrode configurations, namely the dual layer ring, the four layer staggered ring, and the opposed dual plane array, were designed and systematically compared to evaluate their influence on depth sensitivity and spatial resolution. Based on the Tikhonov-Noser hybrid regularization scheme, a region-clustering constraint was introduced to develop the TK-Noser-RCC algorithm. This approach aggregates spatially adjacent elements with similar conductivity variations, thereby enhancing structural continuity and suppressing isolated noise artifacts. To validate the proposed framework, an upper-abdominal physical phantom was constructed using agar to simulate background tissue conductivity. Hemispherical high-conductivity inclusions with volumes ranging from 10 ml to 50 ml were attached to the inner gastric wall to mimic localized bleeding under different gastric filling states. Boundary voltages were acquired under a 120 kHz excitation current and reconstructed using the TK-Noser-RCC algorithm. Furthermore, an in vivo animal experiment was performed using a porcine model with adult-scale abdominal dimensions. A total of 100 ml of autologous blood was injected incrementally into the stomach to simulate progressive gastric hemorrhage, and time-difference EIT reconstruction was conducted at each injection stage to assess the dynamic system response under physiological conditions. ResultsSimulation results demonstrated that the opposed dual-plane electrode array achieved superior depth sensitivity distribution and spatial resolution. For a 40 ml hemorrhage model, the average ICC and SSIM improved by 55.9% and 38.8% compared with the dual-layer ring configuration, and by 64.0% and 39.5% compared with the four-layer staggered configuration. The proposed region-clustering constraint significantly enhanced reconstruction stability. Under added Gaussian noise of 40 dB and 30 dB, ICC values remained approximately 0.85, indicating effective artifact suppression and preservation of boundary integrity. In physical phantom experiments, reconstructed hemorrhage volumes increased approximately linearly with the preset hemispherical volumes, and the reconstructed high-conductivity regions closely matched the actual bleeding locations. Both empty-stomach and full-stomach conditions were evaluated, demonstrating that the opposed dual-plane configuration maintained stable imaging performance across varying gastric contents. In the animal experiment, reconstructed low-impedance regions expanded progressively with increasing injected blood volume. The spatial localization of the hemorrhage remained stable throughout the procedure, and no significant artifacts were observed. Quantitative analysis showed that reconstructed volume and average conductivity variation exhibited an approximately linear growth trend with injected blood volume, confirming the sensitivity of the system to dynamic intragastric conductivity changes. ConclusionThe proposed 3D-gEIT framework enables quantitative reconstruction of gastric hemorrhage volume and spatial distribution with improved depth sensitivity, structural continuity, and noise robustness compared with conventional EIT approaches. By integrating optimized electrode configuration and a region-clustering-constrained reconstruction algorithm, the system provides stable dynamic monitoring under both controlled phantom conditions and in vivo physiological environments. This method offers a noninvasive, real-time, and low-cost imaging strategy for early diagnosis, postoperative monitoring, and bedside surveillance of gastric bleeding.

Objective To evaluate the dissolution effects of pediatric ammonium urate stones in solutions with different pH values, so as to provide reference for the clinical treatment of this type of stones. Methods Eight pure ammonium urate stones(ammonium urate content ≥90%)of similar size and mass(median mass 4.6 g)were obtained from 8 children(＜14 years)undergoing percutaneous nephrolithotomy at the People's Hospital of Xinjiang Uygur Autonomous Region. The stones were placed in sodium chloride solutions with pH values of 5.0, 6.0, 7.0, and 8.5 and artificial urine with pH values of 4. 6, 5.0, 7.0, and 8.5 at a constant temperature of 37 ℃. The mass of the stones was recorded before placement and at 24, 48, and 72 h after placement. The dissolution rates of the stones were calculated. Results The pediatric ammonium urate stones could be dissolved in sodium chloride solution, and the total dissolution rate was the highest(94.6%)after 72 hours when the pH value was 6.0. The total dissolution rate of ammonium urate stones in artificial urine after 72 hours were all over 50%, and the total dissolution rate was the highest(79.7%)when the pH value was 4.6. Conclusion Pediatric ammonium urate stones are soluble in sodium chloride solution and artificial urine, and the total dissolution rate is higher in acidic environment.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

Owing to its inherent advantages—such as being non-destructive, rapid, highly molecule-specific, and minimally interfered with by moisture—Raman spectroscopy has been widely adopted in the fields of skin barrier function assessment, monitoring the transdermal penetration of active cosmetic ingredients, and the identification and quality control of cosmetic products. Despite these strengths, the practical application of this technique faces a significant bottleneck: the strong fluorescence background generated by endogenous skin components and exogenous cosmetic additives. Endogenous skin substances, such as structural proteins (e.g., collagen and elastin), metabolic coenzymes (e.g., nicotinamide adenine dinucleotide), and pigments (e.g., melanin), together with exogenous cosmetic constituents like organic colorants, chemical sunscreens, and fragrances, often possess strong absorption and emission characteristics. When excited by lasers, these components produce a fluorescence background that can be 10⁶ to 10⁸ times stronger than the Raman scattering signals, effectively masking the inherently weak vibrational fingerprint information. In recent years, driven by the rapid development of optoelectronic hardware and artificial intelligence algorithms, fluorescence suppression strategies have evolved from isolated, single-method approaches into comprehensive, multi-level synergistic systems. These systems are categorized into three distinct tiers: sample preparation, signal acquisition, and data processing. At the sample preparation level, techniques such as photobleaching and surface-enhanced Raman spectroscopy (SERS) are employed to eliminate or bypass the generation of fluorescence at the source. At the signal acquisition level, instrumental improvements—including the use of long-wavelength near-infrared excitation (typically 785 nm or 1 064 nm), confocal spatial filtering, and shifted excitation Raman difference spectroscopy (SERDS)— are utilized to physically isolate Raman signals from the fluorescence background. Furthermore, at the data processing level, numerical baseline correction methods such as polynomial fitting, penalized least squares (e.g., airPLS, arPLS), wavelet transform, and derivative algorithms are increasingly integrated into the analytical pipeline to extract Raman spectral features from mixed signals without increasing hardware costs or acquisition time. This review provides a systematic categorization and critical evaluation of these fluorescence suppression methods, detailing their underlying principles, technical advantages, and inherent limitations in diverse experimental setups. By focusing on critical application scenarios—including skin barrier assessment, percutaneous absorption monitoring, the routine quality control of cosmetics, and the emerging field of portable on-site detection—this paper explores the current state of technique selection and optimization. Finally, the article discusses future development trends, emphasizing the necessity of constructing adaptive, tiered suppression strategies, developing intelligent and automated data processing algorithms, and promoting the integration of portable, multi-modal diagnostic devices. The objective of this review is to provide a comprehensive technical reference to facilitate the transition of Raman spectroscopy from a specialized laboratory tool into a routine, robust analytical platform for advancements in skin science and cosmetic research.

Objective: To investigate the characteristics of psychological symptoms and the associated factors among students with close contact to tuberculosis in school settings,so as to provide evidence for school tuberculosis control and mental health interventions. Methods: A cross sectional study was conducted in April 2023 from 4 schools in Hangzhou using a multistage cluster random sampling method. Students identified as close contacts of tuberculosis cases ( n =406) were assigned to the exposure group, while non close contact students ( n =426) were matched at a 1∶1 ratio within the same schools as the non exposure group. A questionnaire survey was employed to collect data on general demographic and family sociological information. Psychological symptoms were assessed using the Symptom Check List-90 (SCL-90). A global severity index (GSI) score ≥2.0 was defined as moderate to severe psychological symptoms (MSPS). Logistic regression analysis was performed to identify associated factors. Results: The overall MSPS detection rate was 15.38%. The detection rate in the exposure group (20.69%) was significantly higher than the non exposure group (10.33%)( χ 2=17.14, P <0.05). Multivariate Logistic regression analysis showed that middle or lower family economic status ( OR =1.90, 95% CI =1.10-3.28) and poor interaction with others ( OR =2.95, 95% CI =1.79-4.88) were independent factors associated with MSPS among the exposure group (both P <0.05). Conclusions Students who are close contacts of school tuberculosis cases have a relatively high MSPS detection rate. Poor family economic status and poor interaction with social personnel are the main factors influencing MSPS. Schools should simultaneously strengthen psychological health support targeting factors in tuberculosis prevention and control.

AIM: To observe the changes of retinal nerve fiber layer(RNFL)thickness and radial peripheral capillary(RPC)density in patients with unilateral branch retinal vein occlusion(BRVO), and further analyze the correlation between RPC density and RNFL thickness.METHODS: Observational study. Totally 37 patients with unilateral BRVO diagnosed at the ophthalmology department of First Hospital of Qinhuangdao from October 2020 to January 2022 were selected, the 37 affected eyes were the unilateral BRVO group, and 37 fellow healthy eyes were the contralateral unaffected group, and 35 healthy individuals(35 right eyes were selected)without ocular diseases during the same period were selected as the normal control group. The best corrected visual acuity, intraocular pressure, anterior segment, fundus and optical coherence tomography angiography(OCTA)were examined in both eyes of all BRVO patients and healthy individuals. The central macular thickness(CMT), the RNFL thickness, and the optic disc-AV crossing distance(DAVD)were measured by built-in software of the OCTA equipment. The optimized U-net algorithm was used to eliminate the large blood vessels, and then the RPC density was calculated. The CMT, RNFL thickness and RPC density were compared among the three groups. And the correlations of the RPC density with the CMT, RNFL thickness, and the DAVD were investigated.RESULTS: Compared with the contralateral unaffected group and the normal control group, the CMT and the RNFL thickness were significantly thickened in the unilateral BRVO group(all P<0.05); there were no statistical differences in the CMT and the RNFL thickness between the contralateral unaffected group and the normal control group(all P>0.05). The RPC density in the unilateral BRVO group increased compared with the contralateral unaffected group and decreased compared with the normal control group, but there was no statistically difference(all P>0.05). However, the RPC density in the contralateral unaffected group decreased compared with the normal control group(P<0.05). The RPC density in the unilateral BRVO group was not correlated with the CMT(P=0.960), but positively correlated with the RNFL thickness(r=0.401, P=0.014)and negatively correlated with the DAVD(r=-0.339, P=0.040).CONCLUSION: The RNFL thickened significantly and the RPC density did not change significantly in the optic disc area of BRVO patients. The RPC density is positively correlated with the RNFL thickness, indicating that the RNFL thickness can be used as a monitoring indicator to analyze and study the damage degree of the RPC density.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*