To address the current issues of data imbalance and scarcity in photoplethysmography (PPG) data for type 2 diabetes mellitus (T2DM) prediction, this study proposes an improved conditional Wasserstein generative adversarial network with gradient penalty (CWGAN-GP). The algorithm integrated gated recurrent unit (GRU) networks and self-attention mechanisms to construct a generator, aiming to produce high-quality PPG signals. Various data augmentation methods, including the improved CWGAN-GP, were employed to expand the PPG dataset, and multiple classifiers were applied for T2DM prediction analysis. Experimental results showed that the model trained on data generated by the improved CWGAN-GP achieved the optimal prediction performance. The highest accuracy reached 0.895 0, and compared with other data enhancement methods, this approach exhibited significant advantages in terms of precision and F1-score. The generated data notably enhances the accuracy and generalization ability of T2DM prediction models, providing a more reliable technical basis for non-invasive early T2DM screening based on PPG signals.
Photoplethysmography/methods* ; Diabetes Mellitus, Type 2/diagnosis* ; Humans ; Algorithms ; Neural Networks, Computer ; Signal Processing, Computer-Assisted ; Prediction Algorithms

Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
Animals ; Alzheimer Disease/pathology* ; Pseudogenes/genetics* ; Mice ; Memory Disorders/metabolism* ; MicroRNAs/genetics* ; Disease Models, Animal ; Spatial Learning/physiology* ; Mice, Transgenic ; Presenilin-1/genetics* ; Male ; Amyloid Precursor Protein Secretases/metabolism* ; Mice, Inbred C57BL ; Aspartic Acid Endopeptidases/metabolism*

AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Objective To investigate the distribution of high-risk human papillomavirus(HR-HPV)subtypes and risk factors in Jiaxing,so as to provide reference for cervical cancer screening in high-risk population.Methods A total of 22 573 women from Zhejiang cervical cancer screening project management system from April to October 2023 were selected for HR-HPV screening,and they were divided into HR-HPV positive group(2045 cases)and negative group(20 528 cases).The medical history data of the patients were analyzed,and the risk factors of HR-HPV infection were analyzed by univariate and multivariate regression analysis.Results The overall HR-HPV infection rate was 9.06％.HPV52 was the most common type in single infection(29.6％),and HPV2 was the most common type in multiple infections(13.0％).There were significant differences between HR-HPV positive group and negative group in age,education level,gravidity,number of abortions and different neighborhoods(P＜0.05).Multivariate Logistic regression analysis showed that age＞45 years old,primary school education or below,gravidity were independent risk factors for HR-HPV infection.Conclusion HPV52 is the predominant type of HR-HPV in Jiaxing.Age＞45 years,primary school education or below,and gravidity are related risk factors for HR-HPV infection.These populations should still focus on screening,which has a pivotal role in the prevention and treatment of cervical lesions.

[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P＜0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P＜0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P＜0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P＜0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P＜0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P＜0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P＜0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.

Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.

Objective Chronic obstructive pulmonary disease(COPD)is a global respiratory disorder characterized by chron-ic inflammation and airflow limitation.Dysregulation of lipid metabolism plays a pivotal role in its progression.This study aimed to explore the expression of the lipid metabolism-related gene GRIM-12 in COPD,and assess the therapeutic potential of its in-hibitor,Danthron.Methods Gene expression datasets GSE10006 and GSE11784 from the Gene Expression Omnibus(GEO)were analyzed to identify GRIM-12 as a lipid metabolism-related gene upregulated in the small airway epithelium(SAE)of COPD patients.Human airway epithelial cells(16HBE)were stimulated in vitro with cigarette smoke extract(CSE)to evaluate GRIM-12 expression and the regulatory effects of Danthron.IL-6 level was assessed by using enzyme-linked immunosorbent assay(ELISA),while reactive oxygen species(ROS)level was quantified via fluorescence probe assays.The involvement of the Nrf2/HO-1 signaling pathway was also investigated.Results GRIM-12 expression was significantly upregulated in the SAE of COPD patients and in CSE-treated 16HBE cells.Molecular docking analysis showed that Danthron had a high binding affinity with GRIM-12,and inhibited its function through hydrogen bonding and hydrophobic interaction.Danthron treatment significantly suppressed CSE-induced GRIM-12 overexpression in v itro,reduced IL-6 secretion,and attenuated ROS production,alleviated oxidative stress and inflammatory responses.Mechanistic studies further revealed that Danthron enhanced cellular antioxidant defenses by activating Nrf2/HO-1 signaling pathway,thereby mitigating CSE-induced oxidative damage and inflammation.It is proved that Danthron regulated COPD-related pathological changes by targeting and inhibiting GRIM-12 expression.Conclusion Danthron effectively alleviates oxidative stress and inflammation in COPD by GRIM-12 expression inhibition and Nrf2/HO-1 signaling pathway activation,offering a promising therapeutic strategy for COPD management.

BACKGROUND:The mechanisms underlying the occurrence of pressure injuries are complex,and it is not entirely clear which factors play a central role in the development of pressure injuries and how these factors operate. OBJECTIVE:To investigate the relationship between Piezo-type mechanosensitive ion channel component 1(Piezo1)and the occurrence of pressure injuries. METHODS:(1)Cellular experiment:Human immortalized keratinocytes(HaCaT)were treated with Yoda1,a Piezo1 agonist,at different concentrations.Cell viability,calcium ion influx,Piezo1,and apoptosis-related protein expression were detected.(2)Animal experiment:Twelve Sprague-Dawley rats were randomly divided into a control group and three experimental groups,with three rats in each group.The control group was not subjected to pressure,while in the three experimental groups,magnets with a thickness of 1,2,and 3 mm were used to press on both sides of the rats'back for 1 hour,respectively,to establish the animal models of pressure injuries.After modeling,all traumatic tissues were excised and subjected to hematoxylin-eosin,Masson,immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:Cellular experiments:The results of live/dead cell staining showed that HaCaT cell apoptosis increased with the increase of Yoda1 concentration(0,2.5,5,and 10 μmol/L),and calcium ion influx increased with the increase of Yoda1 concentration(0,5,and 10 μmol/L),as well as with the prolongation of treatment time.Western blot assay results showed an increase in the expression of BAX,TG2,and PIEZO1 and a decrease in the expression of the expression of Bcl-2 protein in HaCaT cells in 5 and 10 μmol/L Yoda1 groups compared with the control group(0 μmol/L Yoda1).Animal experiments:The results of hematoxylin-eosin and Masson staining showed that the skin structure of the three experimental groups was damaged at the compression site,there was subcutaneous fat liquefaction and necrosis,and collagen was sparse and disorganized,and damage to the skin structure at the compression site was aggravated with the increase of magnet thickness.Immunofluorescence staining and western blot results showed that compared with the control group,the expression of BAX,TG2,Yap1 and PIEZO1 proteins was elevated,and the expression of Bcl-2 proteins was lowered in the three experimental groups.Moreover,the expression of related proteins showed more significant changes with the increase of magnet thickness(pressure).To conclude,skin compression activates PIEZO1,leading to a significant influx of calcium ions.As the pressure increases,this ultimately results in cell apoptosis due to calcium overload.

[Objective] To compare the diagnostic accuracy of three imaging modalities, inlducing CT urography (CTU), contrast-enhanced MRI (CE-MRI), and contrast-enhanced ultrasound (CEUS) in the qualitative diagnosis of renal space-occupying lesions. [Methods] A retrospective analysis was performed on 542 patients with renal lesions confirmed by surgical pathology in our hospital during Jan.2019 and May 2024.The diagnostic results of CTU, CE-MRI and CEUS were compared and analyzed based on the patients' clinical and pathological data. [Results] The diagnostic accuracy rate of CTU, CE-MRI and CEUS were 84.50%, 83.14% and 86.14%, respectively.For the 161 patients who underwent all three examinations, CEUS was significantly more accurate than CTU (84.16% vs. 77.02%, P=0.018), while there was no significant difference between CTU or CEUS and CE-MRI (79.81%) (P>0.05). Further analysis found that for lesions ≤4 cm, the accuracy of the three examinations was as follows: CEUS=CTU 79.55%, CE-MRI 76.14%, with no significant difference (P>0.05). However, for lesions >4 cm, CEUS ranked the first, followed by CE-MRI and CTU (89.73% vs. 84.25% vs. 73.97%), and CEUS and CE-MRI were better than CTU (P<0.05). Additionally, for the diagnosis of clear cell renal carcinoma and benign renal space-occupying lesions, there was no statistically significant difference among the three imaging modalities (P>0.05), while for the qualitative diagnosis of non-clear cell renal carcinoma, CEUS ranked the first, followed by CE-MRI and CTU (83.87% vs. 74.19% vs. 56.45%), and CE-MRI and CEUS were better than CTU (P<0.05). [Conclusion] All of them have important diagnostic value, and the appropriate selection should be based on patients' specifc conditions.CEUS and CE-MRI are more accurate in the qualitative diagnosis of renal space-occupying lesions than CTU, especially for large lesions and non-clear cell carcinoma.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.