Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

Objective:To investigate the correlation between relative fat mass(RFM)and Estimated Glomerular Filtration Rate(eGFR)in an elderly hypertensive population.Methods:This cross-sectional study enrolled elderly hypertensive individuals aged 65 years and older from Huai'an city between June 2023 and December 2023.Clinical data for these subjects were collected, and RFM and eGFR were calculated according to established formulas.Subsequently, the subjects were divided into two groups based on their eGFR levels: the eGFR normal group and the eGFR decreased group.Differences between these two groups were compared.Multivariate logistic regression models were employed to analyze the association between RFM and eGFR, and a subgroup analysis was conducted.The predictive value of RFM for renal function decline was evaluated using receiver operating characteristic curves(ROC).Results:Among the 2, 603 subjects, 921(35.4%)were assigned to the eGFR decreased group, while 1, 682(64.6%)were assigned to the eGFR normal group.The proportion of males, married individuals, smokers, and alcohol drinkers, as well as diastolic blood pressureand cultural levels, were significantly lower in the eGFR decreased group compared to the eGFR normal group (all P<0.05). Conversely, the duration of hypertension, proportion of comorbidities, age, fasting blood glucose, triglycerides, low-density lipoprotein cholesterol(LDL-C), relative fat mass(RFM), visceral fat index(VAI), dysfunctional obesity index(DAI), body roundness index(BRI), and conicity index(C-index)were all significantly higher in the eGFR decreased group compared to the eGFR normal group(all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis revealed that when RFM was treated as a continuous variable, the risk of eGFR decline increased with rising RFM(odds ratio[ OR]=1.035, 95% confidence interval[95% CI]: 1.008-1.063, P=0.010). When grouped according to RFM quartile levels(in ascending order)into Q1(<26.22), Q2(26.22-<30.53), Q3(30.53-<39.26), and Q4(≥39.26), using the Q1 group as a reference, the risk of eGFR decline increased in the Q3( OR=1.691, 95% CI: 1.777-2.430, P=0.004)and Q4( OR=1.743, 95% CI: 1.118-2.717, P=0.014)groups.In the subgroup analysis, gender( P-interaction=0.034)and smoking( P-interaction=0.012)were identified as having significant interaction effects on RFM and the decline in eGFR.In the male subgroup( OR=1.067, 95% CI: 1.027-1.108, Ptrend=0.001)and the smoking subgroup( OR=1.109, 95% CI: 1.026-1.199, Ptrend=0.009), the risk of eGFR decline significantly increased with higher levels of RFM.The restricted cubic spline(RCS)analysis indicated that when RFM exceeded 30.609, the risk of eGFR decline increased with rising RFM levels, demonstrating a non-linear correlation between RFM and the risk of eGFR decline( Pnonlinearity=0.048 5). The ROC curve analysis revealed that the area under the curve(AUC)for RFM in predicting eGFR reduction was 0.635(95% CI: 0.613-0.657, P1<0.001), which was significantly higher than the AUC for VAI(AUC=0.573, 95% CI: 0.550-0.596, P2<0.001), DAI(AUC=0.562, 95% CI: 0.539-0.584, P2<0.001), BRI(AUC=0.564, 95% CI: 0.541-0.587, P2<0.001), and the C-index(AUC=0.536, 95% CI: 0.513-0.559, P2<0.001). Conclusions:Elevated RFM is an independent risk factor for eGFR decline in elderly hypertensive individuals.There exists a significant interaction between gender and smoking with respect to the risk of RFM and eGFR decline.Additionally, RFM demonstrates a notable predictive value for eGFR decline in elderly hypertensive individuals.

Objective:To investigate the miRNA-mRNA regulatory network in a rat model of Tourette syndrome(TS)using transcriptomic technology and to screen key signaling pathways and potential traditional Chinese medicine(TCM)candidates for intervention.Methods:A TS rat model was established using iminodipropionitrile(IDPN).RNA sequencing was performed to identify differentially expressed miRNAs and mRNAs in the brain tissues of TS rats.Bioinformatics analysis was applied to construct interaction networks,and network pharmacology was further employed to screen potential TCM compounds.Results:After 7 days of IDPN modeling,the model group exhibited motor and stereotypical behavioral changes,with behavioral scores greater than 3 points.Hema toxylin-eosin(HE)staining revealed irregular neuronal nuclear morphology,uneven chromatin distribution,nuclear pyknosis,and increased glial cell density.KEGG enrichment analysis identified key pathways:calcium signaling pathway,neuroactive ligand-receptor interaction,p53 signaling pathway,ECM-receptor interaction,and TGF-β signaling pathway.miR-125a-3p,miR-106-3p,and miR-760-3p were identified as pivotal miRNAs.Potential TCM candidates included Ajuga decumbens,Acanthopanax bark,Codonopsis pilosula,Stephania japonica,Os Draconis,Notopterygium root,Siraitia grosvenorii,Zanthoxylum nitidum root,Morinda officinalis,and Corydalis yanhusuo.Conclusion:The miRNAs miR-106-3p,miR-125a-3p,and miR-760-3p may mediate TS pathogenesis by altering critical signaling networks,including the calcium signaling pathway,neuroactive ligand-receptor interaction,and ECM-receptor interaction pathways,leading to neuroimmune inflammation and dopaminergic system dysregulation.TCM compounds such as Corydalis yanhusuo and Ajuga decumbens may exert therapeutic effects through multi-component synergistic regulation of these miRNAs and downstream pathways.

Objective To explore the effect of hyperbaric oxygen combined with synchronous brain bionic electrical stimulation on patients with stroke-related sleep disorders.Methods From November,2023 to November,2024,a total of 68 stroke patients with stroke-related sleep disorders ad-mitted to Huashan Hospital,Fudan University were selected.They were randomly divided into control group(n=34)and experimental group(n=34).The control group received routine hyperbaric oxygen therapy,while the ex-perimental group received routine hyperbaric oxygen therapy combined with synchronous brain bionic electrical stimulation inside the chamber,for four weeks.Pittsburgh Sleep Quality Index(PSQI),sleep-monitoring wrist-bands,Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS)were used to assess the outcomes before and after treatment..Results Four patients in the control group and one in the experimental group dropped out.After treatment,the scores of each factors of PSQI decreased in both groups(t>2.693,P<0.05),and were lower in the experimental group than in the control group(t>2.699,P<0.01),expect hypnotic drug use(P>0.05);the total sleep time,deep sleep time and rapid eye movement sleep time became longer in both groups(|t|>7.270,P<0.001),and they were longer in the experimental group than in the control group(|t|>5.712,P<0.001);the scores of SAS and SDS decreased in both groups(t>9.530,P<0.001),and they were less in the experimental group than in the control group(t>4.740,P<0.001).Conclusion Synchronous brain bionic electrical stimulation in hyperbaric oxygen chamber could effectively prolong the total sleep time,deep sleep time and rapid eye movement time of patients with stroke-related sleep disorders,re-lieve anxiety and depression after stroke,and improve sleep quality.

Objective:To investigate the correlation between relative fat mass(RFM)and Estimated Glomerular Filtration Rate(eGFR)in an elderly hypertensive population.Methods:This cross-sectional study enrolled elderly hypertensive individuals aged 65 years and older from Huai'an city between June 2023 and December 2023.Clinical data for these subjects were collected, and RFM and eGFR were calculated according to established formulas.Subsequently, the subjects were divided into two groups based on their eGFR levels: the eGFR normal group and the eGFR decreased group.Differences between these two groups were compared.Multivariate logistic regression models were employed to analyze the association between RFM and eGFR, and a subgroup analysis was conducted.The predictive value of RFM for renal function decline was evaluated using receiver operating characteristic curves(ROC).Results:Among the 2, 603 subjects, 921(35.4%)were assigned to the eGFR decreased group, while 1, 682(64.6%)were assigned to the eGFR normal group.The proportion of males, married individuals, smokers, and alcohol drinkers, as well as diastolic blood pressureand cultural levels, were significantly lower in the eGFR decreased group compared to the eGFR normal group (all P<0.05). Conversely, the duration of hypertension, proportion of comorbidities, age, fasting blood glucose, triglycerides, low-density lipoprotein cholesterol(LDL-C), relative fat mass(RFM), visceral fat index(VAI), dysfunctional obesity index(DAI), body roundness index(BRI), and conicity index(C-index)were all significantly higher in the eGFR decreased group compared to the eGFR normal group(all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis revealed that when RFM was treated as a continuous variable, the risk of eGFR decline increased with rising RFM(odds ratio[ OR]=1.035, 95% confidence interval[95% CI]: 1.008-1.063, P=0.010). When grouped according to RFM quartile levels(in ascending order)into Q1(<26.22), Q2(26.22-<30.53), Q3(30.53-<39.26), and Q4(≥39.26), using the Q1 group as a reference, the risk of eGFR decline increased in the Q3( OR=1.691, 95% CI: 1.777-2.430, P=0.004)and Q4( OR=1.743, 95% CI: 1.118-2.717, P=0.014)groups.In the subgroup analysis, gender( P-interaction=0.034)and smoking( P-interaction=0.012)were identified as having significant interaction effects on RFM and the decline in eGFR.In the male subgroup( OR=1.067, 95% CI: 1.027-1.108, Ptrend=0.001)and the smoking subgroup( OR=1.109, 95% CI: 1.026-1.199, Ptrend=0.009), the risk of eGFR decline significantly increased with higher levels of RFM.The restricted cubic spline(RCS)analysis indicated that when RFM exceeded 30.609, the risk of eGFR decline increased with rising RFM levels, demonstrating a non-linear correlation between RFM and the risk of eGFR decline( Pnonlinearity=0.048 5). The ROC curve analysis revealed that the area under the curve(AUC)for RFM in predicting eGFR reduction was 0.635(95% CI: 0.613-0.657, P1<0.001), which was significantly higher than the AUC for VAI(AUC=0.573, 95% CI: 0.550-0.596, P2<0.001), DAI(AUC=0.562, 95% CI: 0.539-0.584, P2<0.001), BRI(AUC=0.564, 95% CI: 0.541-0.587, P2<0.001), and the C-index(AUC=0.536, 95% CI: 0.513-0.559, P2<0.001). Conclusions:Elevated RFM is an independent risk factor for eGFR decline in elderly hypertensive individuals.There exists a significant interaction between gender and smoking with respect to the risk of RFM and eGFR decline.Additionally, RFM demonstrates a notable predictive value for eGFR decline in elderly hypertensive individuals.

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

Objective:To retrieve, evaluate, and summarize the best evidence on ultrasound-guided placement and tip confirmation of peripherally inserted central catheter (PICC) in neonates.Methods:Based on the "6S" evidence pyramid model, literature on ultrasound-guided placement and tip confirmation of PICC in neonates was sequentially searched on guideline websites, professional society websites, and journal databases. The search period was from database establishment to September 30, 2024. Two researchers used uniform criteria for independent quality assessment and evidence extraction from the literature, and the extracted evidence was integrated and summarized.Results:A total of ten articles were included, including five guidelines, one clinical decision, two expert consensus, one Meta-analysis, and one evidence summary. Thirty pieces of evidence were developed in six aspects: personnel qualification and training, catheter selection, assessment of placement veins, ultrasound-guided PICC puncture in neonates, PICC tip confirmation in neonates, and prevention and management of malposition.Conclusions:This study summarizes the best evidence for ultrasound-guided placement and tip confirmation of PICC in neonates. It is recommended that evidence be selected and applied to develop a standardized process for neonatal PICC placement in conjunction with the resource environment of the department and the skill level of the healthcare professionals to improve the quality of nursing and to ensure the safe and effective use of the PICC in clinical practice.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.