Objective To identify key influencing factors for comorbidity between myopia and depressive symptoms among middle school students, and to construct a nomogram predictive model capable of quantitatively assessing their comorbidity risk. Methods A total of 13 976 middle school students aged 11-20 from 14 counties (cities, districts) in Yichang City were selected as study subjects through cluster random sampling. On-site surveys were conducted using the Student Health Status and Influencing Factors Questionnaire and the Depression Assessment Scale. Chi-square test and multivariate logistic regression analysis were employed to investigate the comorbidity association between myopia and depressive symptoms and their influencing factors, and to construct a nomogram model for risk prediction. Results The myopia screening rate among middle school students was 68.67%, the depression detection rate was 23.31%, and the comorbidity detection rate was 16.59%. Logistic regression analysis revealed that boarding school (OR=1.207), smoking history (OR=1.504), alcohol consumption (OR=2.016), outdoor activity time <1 h (OR=1.293), internet addiction (OR=4.008), school bullying (OR=4.358), school absence due to illness within one year (OR=1.712), and severe injury within one year (OR=1.356) were risk factors for myopia-depression comorbidity. Protective factors included male gender (OR=0.578), junior high school students (OR=0.670), nuclear family (OR=0.862), moderate-to-high intensity exercise ≥1 h/d (OR=0.852), screen time <2h (OR=0.803), adequate sleep duration (OR=0.602), and homework time after school <2 h/d (OR=0.766). The nomogram model constructed based on the above variables exhibited excellent discriminant power (AUC = 0.712) and calibration (Hosmer-Lemeshow test, χ²=3.245, P> 0.05). Conclusion Factors such as boarding school attendance, smoking history, alcohol consumption, less than 1 hour of daily outdoor activity, internet addiction, and school bullying are significantly associated with the comorbidity of screening myopia and depressive symptoms among middle school students in Yichang City. The nomogram model effectively predicts the comorbidity risk in this population, facilitating timely intervention for high-risk individuals.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The ^“tripartite linkage^” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.

Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.
Humans ; Alzheimer Disease/physiopathology* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/physiology* ; Animals ; Amyloid beta-Peptides/metabolism*

Objective To investigate the effect of the small molecule inhibitor C42 of kallikrein-related peptidase 7(KLK7)on ovarian cancer with elevated expression of KLK7 and evaluate the feasibility of C42 as a new therapeutic strategy for ovarian cancer.Methods The CCK-8 assay,flow cytometry,cell scratch assay,Transwell assay,and Western blotting were employed to assess the effects of C42 on the proliferation,migration,and invasion of the ovarian cancer cell line SKOV3,which was characterized by high KLK7 expression.Additionally,a subcutaneous xenograft model of ovarian cancer was established with SKOV3 cells in nude mice to evaluate the effects of C42 on the tumor growth and metastasis.The expression levels of proteins associated with tumor metastasis and invasion in the tumor tissue were examined by immunohistochemical techniques.Results The cellular experiment showed that C42 suppressed the proliferation,migration,and invasion(all P<0.001)of SKOV3 cells,compared with the control group.The animal experiment showed that compared with the control group,the 10.2 mg/kg C42 group exhibited a decreased tumor weight(P=0.009) and attenuated liver metastases.Immunohistochemical staining revealed that the 10.2 mg/kg C42 group demonstrated down-regulated expression of the tumor proliferation marker Ki-67(P=0.002)and the tumor metastasis and invasion-associated proteins such as matrix metalloproteinase-9(P=0.027)and Vimentin(P=0.039).Conclusion The small molecule inhibitor C42 of KLK7 effectively suppresses the proliferation,migration,and invasion of ovarian cancer SKOV3 cells.
Female ; Humans ; Ovarian Neoplasms/drug therapy* ; Kallikreins/antagonists & inhibitors* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C

Objective:Utilizing the principles of mechanical vibrations dissections and low-temperature coagulation of harmonic scalpel, and combining the magnifying effect of 3D thoracoscopy and the advantage of low trauma, we used harmonic scalpel to harvest the left internal mammary artery (LIMA) under thoracoscopy, and explored the feasibility and early effect of harmonic scalpel in minimally invasive coronary artery bypass grafting (MICABG).Methods:A total of 488 patients who underwent MICABG from July 2021 to December 2023 in Dong E Hospital were collected. Among them, 347 patients was harvested using harmonic scalpel under thoracoscopy. Following anastomosis, the blood flow and pulsatility index (PI) from the graft to the target vessel were determined using a transit time flow meter (MiraQ, Medistim, Norway), and patency was checked. Data from 347 patients were analyzed.Results:All 347 patients were performed under non-extracorporeal circulation and successful graft patency was achieved in all patients. Analysis of 79 patients revealed a median time to LIMA acquisition of 32 min and a median length of acquisition of 15 cm. No graft-related events or complications occurred in any of the patients, and 2 patients died postoperatively. During a median follow-up of 12.1 months, only one patient experienced graft occlusion necessitating intervention.Conclusion:The utilization of harmonic scalpel for LIMA harvesting in MICABG is feasible and yields stable early results.

Objective:Utilizing the principles of mechanical vibrations dissections and low-temperature coagulation of harmonic scalpel, and combining the magnifying effect of 3D thoracoscopy and the advantage of low trauma, we used harmonic scalpel to harvest the left internal mammary artery (LIMA) under thoracoscopy, and explored the feasibility and early effect of harmonic scalpel in minimally invasive coronary artery bypass grafting (MICABG).Methods:A total of 488 patients who underwent MICABG from July 2021 to December 2023 in Dong E Hospital were collected. Among them, 347 patients was harvested using harmonic scalpel under thoracoscopy. Following anastomosis, the blood flow and pulsatility index (PI) from the graft to the target vessel were determined using a transit time flow meter (MiraQ, Medistim, Norway), and patency was checked. Data from 347 patients were analyzed.Results:All 347 patients were performed under non-extracorporeal circulation and successful graft patency was achieved in all patients. Analysis of 79 patients revealed a median time to LIMA acquisition of 32 min and a median length of acquisition of 15 cm. No graft-related events or complications occurred in any of the patients, and 2 patients died postoperatively. During a median follow-up of 12.1 months, only one patient experienced graft occlusion necessitating intervention.Conclusion:The utilization of harmonic scalpel for LIMA harvesting in MICABG is feasible and yields stable early results.

Objective:To investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy,and to compared the single-center data on surgical out-comes with the Surveillance,Epidemiology,and End Results(SEER)database.Methods:This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial ne-phrectomy in the Department of Urology,Peking University Third Hospital(PUTH)from 2010 to 2023.The clinical data and depicting baseline characteristics were collected.Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration(C-CKD-EPI)formulae were used to calculate the estimated glomerular filtration rate(eGFR).The renal function curves over time were then plotted,and the patients were followed-up to record their survival status.Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included,propensity score matching(PSM)was performed to balance the differences between SEER cohort and PUTH cohort,and the cancer-specific survival(CSS)curves for both groups were plotted and statistical differences were calcu-lated by the Kaplan-Meier method.Results:A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort,respectively,and 31 and 72 patients were screened in each cohort after PSM.Of the baseline characteristics,only tumor size(P=0.042)was found to differ statistically between the two groups.There was no statistically significant difference between the two cohorts in terms of CSS after PSM(P=0.556).The median follow-up time in the SEER cohort was 112.5(65,152)months and a 10-year survival rate of 97.2％,while the PUTH cohort had a median follow-up of 57.0(20,1 172)months and a 10-year survival rate of 100.0％.There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation(P=0.073).There was a statistically significant difference in eGFR among the preoperative,short-term postoperative,and long-term postoperative(P＜0.001),which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period.Conclusion:Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.