ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveTo investigate the therapeutic effect of Shaoyao Gancaotang （SYGCT） on high-fat diet （HFD）-aggravated colitis induced by dextran sulfate sodium （DSS） in mice and decipher the potential mechanism. MethodsForty male C57BL/6J mice were fed an HFD for 14 days， followed by gavage of 2%DSS for 7 days for the modeling of HFD-aggravated colitis. The mice were randomly allocated into control， model （HFD-aggravated colitis）， low-dose （5.2 g·kg^-1） SYGCT， high-dose （10.4 g·kg^-1） SYGCT， and 5-aminosalicylic acid （5-ASA， positive control， 50 mg·kg^-1） groups. Body mass changes and disease activity index （DAI） scores were recorded. The colon length was measured. Pathological changes in the colon tissue were observed through hematoxylin-eosin （HE） staining. Transcriptomic analysis was performed to identify differentially expressed genes. Western blot was employed to quantify the protein levels of Occludin， Claudin3， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with the control group， the model group exhibited diarrhea， bloody stools， increased DAI scores （P<0.01）， colon shortening （P<0.01）， severe colonic pathological damage， and reduced expression of tight junction proteins Occludin and Claudin3 （P<0.05， P<0.01）. Transcriptomic analysis revealed that the differentially expressed genes between the high-dose SYGCT group and the model group were significantly enriched in the ferroptosis signaling pathway. Compared with the model group， SYGCT treatment alleviated diarrhea and bloody stools， reduced DAI scores （P<0.01）， increased the colon length （P<0.01）， mitigated colonic pathological damage， and upregulated the expression of Occludin and Claudin3 （P<0.01）， as well as proteins （SLC7A11， GPX4， and FTH1） associated with the inhibition of ferroptosis （P<0.05）. ConclusionSYGCT significantly ameliorates HFD-aggravated DSS-induced colitis by suppressing ferroptosis via activation of the SLC7A11/GPX4 pathway.

ObjectiveTo dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. MethodsTwenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. ResultsCompared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. ConclusionThe vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.

ObjectiveTo dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. MethodsTwenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. ResultsCompared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. ConclusionThe vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

OBJECTIVES: We propose a new melanoma segmentation model, SG-UNet, to enhance the precision of melanoma segmentation in dermascopy images to facilitate early melanoma detection. METHODS: We utilized a U-shaped convolutional neural network, UNet, and made improvements to its backbone, skip connections, and downsampling pooling sections. In the backbone, with reference to the structure of VGG, we increased the number of convolutions from 10 to 13 in the downsampling part of UNet to achieve a deepened network hierarchy that allowed capture of more refined feature representations. To further enhance feature extraction and detail recognition, we replaced the traditional convolution the backbone section with self-calibrated convolution to enhance the model's ability to capture both spatial and channel dimensional features. In the pooling part, the original pooling layer was replaced by Haar wavelet downsampling to achieve more effective multi-scale feature fusion and reduce the spatial resolution of the feature map. The global attention mechanism was then incorporated into the skip connections at each layer to enhance the understanding of contextual information of the image. RESULTS: The experimental results showed that the SG-UNet model achieved significantly improved segmentation accuracy on ISIC 2017 and ISIC 2018 datasets as compared with other current state-of-the-art segmentation models, with Dice reached 92.41% and 86.62% and IoU reaching 92.31% and 86.48% on the two datasets, respectively. CONCLUSIONS The proposed model is capable of effective and accurate segmentation of melanoma from dermoscopy images.
Melanoma/diagnosis* ; Humans ; Neural Networks, Computer ; Dermoscopy/methods* ; Skin Neoplasms ; Image Processing, Computer-Assisted/methods* ; Calibration ; Algorithms

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*