Objective: To investigate the longitudinal associations between dietary patterns in early childhood and myopia among children, so as to provide evidence for improving early childhood dietary patterns and promoting healthy ocular development among children. Methods: Participants were derived from the Ma-anshan Birth Cohort (MABC). A total of 1 432 children were included. Dietary patterns at 2.5 years of age were collected in 2017 using a food frequency questionnaire completed by parents. In 2022, cycloplegic refraction and ocular biometric parameters were measured in children aged 7-8 years. Food components were grouped into tertiles ( T1-T 3), and latent class analysis (LCA) was used to identify dietary pattern at the age of 2.5. Log-binomial regression and multiple linear regression model were applied to examine the associations of dietary patterns and their latent classes with myopia, spherical equivalent (SE), and axial length (AL). Results: The prevalence of myopia among children was 23.9%. After adjusting for covariates, the T 2 group of cereals and tubers was negatively associated with myopia rate ( RR=0.72, 95%CI =0.57-0.90) and AL ( β=-0.15, 95%CI =-0.24 to -0.05), and positively associated with SE ( β=0.21, 95%CI =0.06-0.35)(all P ＜0.05). Linear regression models showed that the T 2 group of fruits and vegetables was positively associated with AL ( β=0.09, 95%CI =0.00- 0.19 ); the T 3 group of high sugar foods ( β=0.11, 95%CI =0.00-0.21) and the T 3 group of processed foods ( β= 0.10 , 95%CI =0.00-0.19) were positively associated with AL; total scores for high sugar foods ( β=0.07, 95%CI =0.00-0.14) and processed foods ( β=0.09, 95%CI =0.01-0.17) were positively associated with AL (all P <0.05). After adjusting for sex, age, and parental myopia, the comprehensive high intake pattern was positively associated with AL ( β=0.12, 95%CI =0.00-0.23, P <0.05). After further adjusting for daily screen time and daily outdoor activity time, the association was no longer statistically significant ( β= 0.11 , 95%CI =-0.00-0.23, P >0.05). Conclusions Moderate consumption of cereals and tubers in early childhood may reduce the risk of myopia and delay AL growth. In contrast, high sugar and highly processed diets may promote AL and increase myopia risk. Establishing healthy dietary habits in early childhood and limiting intake of high sugar and processed foods is crucial for promoting ocular development in children.

Objective To investigate the influencing factors of advanced bone age in early adolescence, and to provide a scientific basis for the early identification of children and adolescents with abnormal bone age development. Methods A prospective cohort study design was adopted. From July 2022 to September 2023, height, weight, and body composition data of children were collected, with the baseline age of the study participants being 8.42±0.50 years. Subsequently, from March 2024 to November 2025, these children in the cohort were followed up and their bone age development was monitored. In the end, a total of 1142 participants with complete data were included in the study. Results In early adolescence, there were 239 individuals (20.93%) with early bone age development and 103 (9.02%) with delayed development. The proportion of early bone age development was higher among individuals whose mothers had gestational hypertension during pregnancy, and the difference was statistically significant (χ²=8.90, P<0.05). The proportion of early bone age development was higher among boys, and the difference was statistically significant (χ²=41.69, P＜0.001). Disordered multiclass logistic regression analysis showed that after adjusting for demographic factors, overweight (OR=2.65, 95%CI:1.81-3.88), obesity (OR=6.51, 95%CI: 4.45-9.53), and excessive body fat percentage (OR=4.60, 95% CI: 3.01-7.03) were associated with an increased risk of early bone age development in children and adolescents. Conclusion Being overweight/obese and having an excessive body fat percentage can increase the risk of early bone age development in adolescents.

Objective: To explore the association between the triglyceride-glucose-frailty index and the risk of diabetes mellitus among middle-aged and elderly population, so as to provide the evidence for diabetes mellitus risk screening and management among middle-aged and elderly population. Methods: Based on data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, middle-aged and elderly individuals aged ≥45 years without diabetes mellitus at baseline were selected as study participants. Demographic characteristics, lifestyles, and laboratory test data were collected. The triglyceride-glucose index was calculated using triglyceride and fasting blood glucose levels, and the frailty index was derived from a 29-item health deficit accumulation model. The triglyceride-glucose-frailty index was obtained by multiplying the two indices, and participants were divided into four groups according to quartiles. Association between the triglyceride-glucose-frailty index and diabetes mellitus incidence risk was analyzed using a multivariable Cox proportional hazards regression model, and the dose-response relationship was assessed using a restricted cubic spline model. Results: A total of 5 246 participants were included, including 2 364 males (45.06%) and 2 882 females (54.94%). The mean age was (58.38±8.78) years. The median of the triglyceride-glucose-frailty index was 0.78 (interquartile range, 1.13). By 2018, 452 diabetes mellitus cases were identified, with a cumulative incidence of 8.62%. Multivariable Cox proportional hazards regression analysis showed that, after adjusting for demographic characteristics, lifestyle factors, and biochemical indicators, each one-standard-deviation increase of the triglyceride-glucose-frailty index was associated with a 37.5% higher risk of diabetes mellitus incidence (HR=1.375, 95%CI: 1.278-1.479). Compared with the Q1 group, the risk increased by 50.8% (HR=1.508, 95%CI: 1.072-2.123), 91.3% (HR=1.913, 95%CI: 1.380-2.651) and 241.6% (HR=3.416, 95%CI: 2.499-4.671) in the Q2, Q3 and Q4 groups, respectively, presenting an upward trend (Pfor trend <0.05). Restricted cubic spline analysis showed a non-linear relationship between the triglyceride-glucose-frailty index and diabetes mellitus incidence risk (P<0.05). Conclusion The triglyceride-glucose-frailty index was positively associated with diabetes mellitus risk among middle-aged and elderly population, and a nonlinear dose-response relationship was observed between the two.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Hepatic Stellate Cells/physiology* ; Disease Progression ; Signal Transduction/physiology* ; Transforming Growth Factor beta/metabolism* ; Cell Proliferation ; Hedgehog Proteins/metabolism* ; Tumor-Associated Macrophages ; Platelet-Derived Growth Factor/metabolism* ; Cell Communication/physiology*