Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

Purpose To investigate the diagnostic value of 18F-FDOPA PET/CT imaging and semi-quantitative analysis platform for the diagnosis of Parkinson's disease(PD).Materials and Methods There were 27 healthy controls and 56 clinically diagnosed PD patients,including 33 early PD(Hoehn-Yahr class Ⅰ-Ⅱ)and 23 advanced PD(Hoehn-Yahr class Ⅲ-Ⅳ),underwent 18F-FDOPA PET imaging in Nanjing First Hospital,Nanjing Medical University were consecutively enrolled from January 2018 to December 2019.The striatal to occipital ratio(SORs)in radioactivity was calculated by HERMES BRASS platform,thereby completing the semi-quantitative analysis of the brain based on regions of interest and observing the asymmetry of the striatal subregions in early-stage PD and late-stage PD patients.Using artificial intelligence techniques to perform principal component analysis on the SORs of the striatal subregions in PD group and healthy control group,the degree of data aggregation and the distinguishability between groups were observed.Results The SORs was significantly reduced in the whole caudate,anterior,posterior putamen and striatum of advanced PD patients(t=9.02-11.72,P<0.000 1).The area under the curve was 0.952,0.973,0.995 and 0.982,respectively.Compared with the healthy control group,the loss of striatal asymmetry index(mean)in each subregion of the striatum in early PD group was caudate(7.61±5.50)%,anterior putamen(11.43±8.97)%,posterior putamen(17.17±11.63)%,and whole striatum(10.65±7.46)%,respectively.The uptake of 18F-FDOPA in the striatum of PD patients was significantly reduced,and the most obvious loss of early PD patients was contralateral posterior putamen,with a decrease of 34%.Conclusion The platform semi-quantitative analysis of 18F-FDOPA PET/CT images provides objective semi-quantitative values for early diagnosis and differential diagnosis of PD.Asymmetry in the striatum,especially in the putamen,may be an important parameter for early diagnosis of PD..

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To investigate the potential of immune-inflammatory markers and the characteristics of magnetically controlled capsule endoscopy in distinguishing gastric adenocarcinoma from precancerous lesions,as well as to develop and validate a risk prediction model.Methods Retrospective analysis was conducted on medical records of 578 patients who underwent magnetic controlled capsule endoscopy at our hospital between January 2021 and December 2023.Following the principle of Pareto's law(80/20 rule),they were randomly divided into a training set(462 cases)and a validation set(116 cases).Magnetic controlled capsule endoscopy and blood cell tests were performed,with pathological diagnosis results serving as the"gold standard",to classify patients into groups of gastric adenocarcinoma and precancerous lesions.The magnetic controlled capsule endoscopic features,neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR)in patients with gastric adenocarcinoma and precancerous lesions were compared to develop and validate a risk diagnostic model for gastric adenocarcinoma.Results Among the 462 patients who underwent magnetic controlled capsule endoscopy,gastric adenocarcinoma was diagnosed in 76 cases through pathological examination,accounting for 16.45%(76/462),while precancerous lesions were observed in 386 cases,accounting for 83.55%(386/462).In the validation set of 116 patients who underwent gastric endoscopy,there were 22 cases of gastric adenocarcinoma,representing an incidence rate of 18.97%(22/116),and a total of 94 cases with precancerous lesions,accounting for an incidence rate of 81.03%(94/116).No statistically significant differences(P＞0.05)were found between the two groups regarding lesion size,border appearance,mucus presence or lesion morphology.However,compared to the precancerous lesion group,the proportion of whitish coloration as well as irregular surface microstructure and grid-like microvessels was significantly higher in the gastric adenocarcinoma group(P＜0.05).Moreover,both NLR and PLR values were significantly higher in the gastric adenocarcinoma group compared to those in the precancerous lesion group(P＜0.05).Irregular surface microstructure(OR=2.213,95%CI:1.288～3.801),irregular grid-like microvessels(OR=2.489,95%CI:1.458～4.249),NLR(OR=2.369,95%CI:1.389～4.046),and PLR(OR=3.016,95%CI:1.767～5.148)were identified as risk factors for gastric adenocarcinoma(P＜0.05).The sensitivity of the risk model for diagnosing gastric adenocarci-noma in the training set was 0.800(95%CI:0.716～0.891),with a specificity of 0.783(95%CI:0.694～0.851)and an area under the curve of 0.858(95%CI:0.787～0.931).In the validation set,the sensitivity for diagnosing gastric adenocarcinoma was 0.861(95%CI:0.771～0.945),with a specificity of 0.769(95%CI:0.683～0.841)and an area under the curve of 0.844(95%CI:0.765～0.923).Conclusion The surface microstructure,microvas-cular morphology,NLR,and PLR of gastric lesions are correlated with the occurrence of gastric adenocarcinoma.Developing a risk diagnostic model facilitates early identification and diagnosis of gastric adenocarcinoma.

ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg^-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg^-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.

Lung cancer is the fastest-growing cancer type in terms of incidence and mortality worldwide， posing a huge threat to the health and life of the population. Radiation therapy is one of the main methods for treating lung cancer， and there is a clear dose-effect relationship between the radiation dose and local control rate of lung cancer. However， the lung is a radiation dose-limiting organ， and the radiation resistance of lung cancer tissues and the radiation damage to normal tissues limit the radiation efficacy for lung cancer. The pathogenesis of lung cancer in traditional Chinese medicine （TCM） is characterized by an initial deficiency in vital Qi， followed by the internal invasion and gradual accumulation of pathogenic Qi. After radiation therapy for lung cancer， the body's vital Qi becomes weaker， and syndromes of phlegm coagulation， Qi stagnation， and static blood blocking collaterals become more severe， leading to radiation resistance of lung cancer tissues. Therefore， the key issue to better clinical efficacy of radiation therapy for lung cancer patients is to use drugs to enhance the radiation sensitivity of lung cancer cells and improve the radiation tolerance of normal lung tissues. TCM can be used as a radiation sensitizer by regulating the cell cycle to increase the proportion of cells in the radiation-sensitive phase， promoting upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes to induce cell apoptosis， enhancing DNA damage caused by radiation and inhibiting damage repair， improving blood circulation and tissue oxygen supply， and so on， to enhance the sensitivity of tumor cells to radiation and amplify the toxicity of radiation to tumor tissues. TCM can also be used as a radiation protector by inhibiting cell damage， regulating cytokines and immune balance， reducing the release of inflammatory and fibrotic factors， and inhibiting the activation of related signaling pathways to prevent and treat radiation-induced lung injury. This article systematically reviewed the research results of TCM on radiation sensitization and radiation protection in lung cancer in recent years， aiming to elucidate the mechanism of TCM in regulating the effect of radiation therapy for lung cancer and provide more theoretical and practical basis for TCM to participate in improving the prognosis of lung cancer patients undergoing radiation therapy.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Injury monitoring is an important approach for injury control and is an important part of comprehensive disease monitoring. With the development of medical digitalization, an intelligent injury monitoring system has been created in Yinzhou District, Ningbo City, Zhejiang Province using artificial intelligence techniques based on Ningbo Municipal Health Information Platform and has been applied across the district since 2019. The manual card-reporting mode has been transformed to intelligent card-reporting mode in this system, which achieves functions of epidemiological analyses of the monitoring data, early warning of high-incidence injuries, classified management of injury and quality control of report cards. Nearly 300 thousand cards have been automatically reported since the system was online available since November 2022, and the epidemiological characteristics of injury were preliminarily understood, which provide data supports to early earning and interventions of injury. The intelligent injury monitoring system greatly improves the injury monitoring efficiency and card-reporting quality, and saves a large number of manpower and material resources, which provides a powerful technical support to widespread injury monitoring.

AIM: To investigate the molecular mechanism through which DKK1 is transcriptionally regulated in HCC (hepatocellular carcinoma) cells. METHODS: Real time PCR was used to explore whether EGFR was involved in regulating DCLK1 mRNA expression in HCC cells; Western blot assay was used to examine whether EGFR-mediated the up-regulation of DCLK1 protein in HCC cells; Immunohistochemical (IHC) analyses were used to examine the protein expression of EGFR and DCLK1 in 39 human HCC tumor specimens. RESULTS: EGF promoted the expression of DCLK1 mRNA and protein in HepG2 and Huh-7 cells (P<0.05, P<0.01), while knockdown of EGFR with two specific siRNA could reverse EGF-induced the up-regulation of DCLK1 mRNA and protein (P<0.01). IHC analyses revealed that the amount of EGFR correlated significantly with that of DCLK1 (r=0.669 6). CONCLUSION: EGFR promoted DCLK1 transcription in HCC.