Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

AIM: To investigate the effect and potential mechanism of liraglutide(LIR)combined with neural stem cells(NSCs)in alleviating diabetic retinopathy(DR)in rats.METHODS:A DR rat model was established using a high-fat diet combined with a single intraperitoneal injection of streptozotocin(STZ). Rats in the control group were fed a normal diet and received an intraperitoneal injection of citric acid-sodium citrate buffer. After modeling, the rats were divided into the control group, DR group, DR+LIR group, DR+BMSCs group, DR+NSCs group, DR+BMSCs+LIR group, and DR+NSCs+LIR group. According to the grouping instructions, rats were given intraperitoneal injection of LIR at 200 μg/(kg·d)and intravitreal injection of bone marrow mesenchymal stem cells(BMSCs), or NSCs, or the combined therapy accordingly for 8 wk. Fasting blood glucose(FBG)and serum insulin levels, as well as retinal oxidative stress indexes and serum inflammatory indexes, were detected in each group. Retinopathy was evaluated by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by TUNEL staining, SIRT1 expression in retinal tissues was detected by immunohistochemistry, and BDNF expression in retinal tissues was detected by immunofluorescence. The transcriptional levels of cZNF532, miR-29a-3p, SIRT1, TGF-β1, NRF2, Keap1, and BDNF in retinal tissues were detected by qRT-PCR, and the protein expression levels of SIRT1, TGF-β1, SMAD2/3, p-SMAD2/3, NRF2, Keap1, p65, and p-p65 in retinal tissues were detected by Western blot. RESULTS:Compared with the other groups of rats, the retinal morphology of rats in the DR+NSCs+LIR group was significantly improved, the levels of FBG, TNF-α, IL-1β, IL-6 and MDA were decreased(all P<0.05), the serum insulin level and the levels of SOD, CAT, and GSH-Px were increased(all P<0.05), the TUNEL-positive rate of retinal cells was reduced(all P<0.05). The expression levels of cZNF532, SIRT1, NRF2, and BDNF in retinal tissue were up-regulated(all P<0.05), whereas the expression levels of miR-29a-3p, TGF-β1, p-SMAD2/3, Keap1, and p-p65 were down-regulated(all P<0.05). CONCLUSION:LIR combined with NSCs alleviates DR by regulating the cZNF532-miR-29a-3p-SIRT1 network and its downstream TGF-β/SMAD, NF-κB, and Keap1/NRF2 signaling pathways.

Clonorchis sinensis primarily lives in the host liver and biliary system, leading to serious health issues, such as hepatobiliary lesions and cholangiocarcinoma. Establishment of rapid, sensitive and specific tools is of great significance for early diagnosis and management of clonorchiasis. Recently, molecular biological techniques have been widely used for detection of C. sinensis infections. This review summarizes the advances in the major molecular assays for detection of C. sinensis infections in intermediate and definite hosts, including PCR, loop-mediated isothermal amplification, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins system, and high-throughput sequencing, and summarizes the characteristics and application prospects of these assays, so as to provide precision detection and management of C. sinensis infection.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Objective:To explore the predictive value of preoperative CT angiography (CTA) for incomplete endothelialization of the occluder after left atrial appendage closure (LAAC) in patients with atrial fibrillation.Methods:The clinical data of 92 atrial fibrillation patients underwent LAAC in the Tangdu Hospital of Air Force Military Medical University from January 2022 to June 2024 were retrospectively analyzed. CTA examinations were performed both before operation and 3 months after operation. Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening, diameter of anchoring area and effective depth were measured. After operation, the condition of occluder endothelialization was evaluated, and the patients were divided into the completely endothelialization group and the incomplete endothelialization group. Multivariate Logistic regression analysis was used to analyze the independent risk factors of occluder incomplete endothelialization after LAAC in patients with atrial fibrillation. The predictive value of independent risk factors was evaluated by the receiver operating characteristic (ROC) curve.Results:Among the 92 patients, CTA 3 months after the operation showed that 58 cases had complete occluder endothelialization (complete endothelialization group), and 34 cases had occluder incomplete endothelialization (incomplete endothelialization group). Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening and diameter of anchoring area in incomplete endothelialization group were significantly larger than those in complete endothelialization group: (28.35 ± 1.77) mm vs. (26.21 ± 2.21) mm, (22.09 ± 2.01) mm vs. (20.86 ± 1.75) mm, (512.76 ± 63.35) mm 2 vs. (453.83 ± 75.39) mm 2 and (24.71 ± 2.50) mm vs. (23.12 ± 2.40) mm, and there were statistical differences ( P<0.01); there was no statistical difference in effective depth between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the long diameter of left atrial appendage opening before operation was an independent risk factor for occluder incomplete endothelialization after LAAC in patients with atrial fibrillation ( OR = 2.141, 95% CI 1.217 to 3.768, P<0.01). ROC curve analysis result showed that the area under the curve of the long diameter of left atrial appendage opening before operation for predicting occluder incomplete endothelialization after LAAC in patients with atrial fibrillation was 0.768 (95% CI 0.674 to 0.862, P<0.01), the optimal cut-off value was 26.5 mm, the sensitivity was 88.2%, and the specificity was 55.2%. Conclusions:A larger long diameter of left atrial appendage opening before operation can lead to occluder incomplete endothelialization after LAAC in patients with atrial fibrillation.

Objective To explore the correlation between stroke etiology and clinical and imaging features in patients with acute ischemic stroke(AIS)due to large vessel occlusion treated by intravascular thrombectomy.Methods A total of 213 patients with AIS and endovascular embolectomy in our hospital from Oct.2016 to Jun.2018 were enrolled retrospectively.According to the etiological classification criteria of Trial of Org 10172 in Acute Stroke Treatment(TOAST),there were 116 cases of cardioembolism and 97 cases of non-cardioembolism.Multivariate logistic regression analysis was used to screen the clinical and imaging characteristics for identifying cardioembolism and non-cardioembolism.Results Compared with non-cardioembolism AIS,cardioembolism AIS was associated with higher NIHSS scores(adjusted odds ratio[OR]=1.09,95%confidence interval[95%CI]1.01-1.18,P=0.02),atrial fibrillation(adjusted OR=76.46,95%CI 26.75-218.51,P＜0.01),absence of hypertension(adjusted OR=0.32,95%CI 0.12-0.84,P=0.02),antiplatelet drug use(adjusted OR=5.03,95%CI 1.22-20.63,P=0.03),shorter onset-to-puncture time(adjusted OR=0.998,95%CI 0.996-1.000,P=0.04),and presence of hyperdense artery sign(HAS)(adjusted OR=4.45,95%CI 1.47-13.49,P=0.01).Conclusion There are some differences in clinical and imaging characteristics between patients with cardioembolism and non-cardioembolism AIS.The occurrence of HAS suggests a higher probability of cardioembolism in AIS patients.