ObjectiveTo determine whether Jinshui Huanxian component formula Ⅱ （ECC-JHF Ⅱ） and matrix hardness interfere with the process of epithelial-mesenchymal transition （EMT） during pulmonary fibrosis by regulating integrin β₁ （ITG β₁）， and to elucidate the underlying mechanism. MethodsA pulmonary fibrosis mouse model was established by a single intratracheal instillation of bleomycin （BLM）. To observe the disease progression at various time points， the mice were sacrificed before modeling and on days 7， 14， 21， 28 and 42 after modeling for assessment of relevant indicators. To evaluate the therapeutic effect of drug intervention， the mice were given ECC-JHF Ⅱ and pirfenidone （PFD） by gavage starting on day 29 after modeling for 14 days of treatment， after which the mice were sacrificed. Pulmonary function， pathological changes， collagen deposition， lung tissue hardness and EMT markers were detected. Polyethylene glycol （PEG） composite hydrogels with different hardness were prepared in vitro using biomaterials such as eight-arm polyethylene glycol thiol （PEG-SH） and eight-arm polyethylene glycol maleimide （PEG-MAL）. Human type Ⅱ alveolar epithelial cells cultured in hard matrix culture dishes were treated with low， medium， and high doses of ECC-JHF Ⅱ （15.31， 30.63， 61.25 mg·L^-1） to observe the intervention effect of ECC-JHF Ⅱ on EMT induced by transforming growth factor beta 1 （TGF-β₁）. Human type Ⅱ alveolar epithelial cells cultured on soft （3.8 kPa） and hard （culture dishes， ~ GPa） matrices were treated with ECC-JHF Ⅱ， respectively. The mRNA and fluorescence expression levels of the epithelial marker E-cadherin （CDH1）， the mesenchymal marker N-cadherin （CDH2） and vimentin （VIM）， as well as ITG β₁， were detected by real-time quantitative polymerase chain reaction （Real-time PCR） and immunofluorescence. Western blot was used to detect the protein expression of CDH1， CDH2 and ITG β₁， and the biomechanical mechanism of ECC-JHF Ⅱ on EMT and pulmonary fibrosis was further verified by knocking down and specific activation of ITG β₁. ResultsECC-JHF Ⅱ treatment improved BLM-induced pulmonary fibrosis in mice， as evidenced by significantly increased minute ventilation （MV） and 50% expiratory flow at tidal volume （EF₅₀） （P<0.05）， and significantly increased tidal volume （TV） after treatment （P<0.01） compared with the model group. Immunohistopathological analysis revealed attenuated inflammation and alveolar injury， reduced deposition of type Ⅰ collagen （Col-Ⅰ）， and significantly decreased lung tissue stiffness （P<0.01）， thereby alleviating disease progression. The real-time PCR results showed that， compared with the model group， the ECC-JHF Ⅱ group showed increased CDH1 expression and decreased CDH2 and VIM expression in mouse lung tissues （P<0.05， P<0.01）， indicating that ECC-JHF Ⅱ inhibited the EMT process to ameliorate pulmonary fibrosis. In vitro experimental results showed that both ECC-JHF Ⅱ and matrix softening reversed the EMT phenotype switch. Specifically， compared with the hard matrix group， the cells cultured on the soft matrix exhibited significantly upregulated expression of the epithelial marker CDH1 （P<0.01） and significantly downregulated expression of the mesenchymal markers CDH2 and VIM （P<0.05）. Furthermore， ECC-JHF Ⅱ inhibited the expression of ITG β₁ both in vitro and in vivo. Knockdown and specific activation of ITG β₁ further confirmed that ITG β₁ is involved in the regulatory process by which ECC-JHF Ⅱ inhibits EMT and ameliorates pulmonary fibrosis. ConclusionECC-JHF Ⅱ and matrix softening can block the EMT process and ameliorate pulmonary fibrosis， and the underlying mechanism may be associated with the inhibition of ITG β₁-mediated mechanotransduction. This study reveals a novel mechanism of ECC-JHF Ⅱ intervention in pulmonary fibrosis from a biomechanical perspective.

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*

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

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:To explore and compare the clinical application value of 8-channel head phased-array coil, an 8-channel temporomandibular joint (TMJ)-specific surface coil, and a single-channel surface coil in TMJ MRI examinations.Methods:A total of 600 temporomandibular disorders (TMD) patients (1 200 joints) who underwent TMJ MRI examination in the First People′s Hospital of Jinzhong from June 2020 to January 2025 were retrospectively screened. Based on inclusion/exclusion criteria, 120 TMD patients (240 joints) with closed-mouth oblique sagittal proton density weighted imaging (OSag PDWI), coronal T2 fat-suppression weighted imaging (OCor fs T2WI) and open-mouth oblique sagittal proton density weighted imaging (OSag PDWI) were included. Patients were divided into groups A, B, and C, with 40 cases in each group. Group A (31female, 9male, median age 24 years old), underwent 8-channel head phased-array coil imaging. Group B (29 female, 11male, median age 23.5 years old) underwent TMJ imaging with an 8-channel surface coil. Group C (29 female, 11male, median age 22.5 years old) underwent single-channel surface coil imaging. There were no significant differences in age, gender, type or disease types among groups ( P>0.05). Six healthy volunteers without TMD (4 female, 2 male, range 19 to 45 years old) underwent imaging with all three coils as self-control. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image quality were compared for five regions of interest (ROI) in both patients and volunteers. Results:Under the same sequence and the same parameters, SNR and CNR in group B were higher than those in group A, and SNR and CNR in group C were also higher than those in group A, the differences were statistically significant ( P<0.05). However, there were significant differences in SNR and CNR between group B and group C in the closed and open positions of ROI1, the open positions of ROI3 and the open positions of ROI5 ( P<0.05), and there were no significant differences in other positions ( P>0.05). Group B had the best image quality, followed by group C and group A had the worst image quality. There were significant differences in the visualization of OSag PDWI in the closed mouth position, OCor T2WI in the coronal position, and OSag PDWI in the open mouth position, such as condyle, anterior attachment, joint disc, double lamina area, joint cavity and lateral pterygoid muscle ( P<0.05). There were significant differences between group B and group C in showing the joint cavity in the closed mouth position and showing the structure of the bilaminar area in the open mouth position ( P<0.05). There was no significant difference in other regions of interest ( P>0.05). The subjective scores of condyle, anterior attachment, articular disc, bilaminar area, articular cavity, lateral pterygos muscle and other structures were medium to high in group A, high in group B, and high or high in group C by two radiologists independently. In the five rois, the 8-channel TMJ surface coil showed more details, especially in the articular disc, condyle and lateral pterygoid muscle regions, and had more advantages in both volunteers and patients. Conclusions:The 8-channel TMJ-specific surface coil provides significantly clearer visualization of critical anatomical details within the ROIs, demonstrating the highest clinical application value and is recommended as the preferred choice.

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.

OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.