BACKGROUND:Disruption of biological rhythms(circadian rhythms)is a typical problem associated with aging.Maintaining the normal function of biological rhythms may be a promising anti-aging strategy.Expression of nuclear factor erthroid 2-related factor 2(Nrf2)is biologically regulated.The glycogen synthase kinase 3(GSK3)system represents a"regulatory valve"that controls subtle oscillations in Nrf2 levels.Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress.However,the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling. OBJECTIVE:To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field. METHODS:The bibliographic method was used to search,review and screen the relevant literature using the keywords of"glycogen synthase kinase 3,nuclear factor erthroid 2-related factor 2,biorhythms and aging"to lay a theoretical foundation for the analysis of the whole paper.Comparative analysis method,through reading and analyzing the obtained literature,was performed to compare the similarities and differences between the literature,thereby providing reasonable theoretical support for the argument.Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION:GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes.GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms.In addition,GSK3/Nrf2 is involved in several metabolic pathways,including those associated with age-related diseases(type 2 diabetes and cancer)and neurodegenerative diseases.

Objective To develop and validate a model to predict the risk of radiation-induced lung injury (RILI) and assess its clinical feasibility. Methods Clinical data from 125 patients with non-small cell lung cancer (NSCLC) were included in the study. The patients were divided into training group (88 cases) and validation group (38 cases). Key predictive factors were identified using univariate and multivariate logistic regression analyses combined with least absolute shrinkage and selection operator (LASSO) regression. A predictive model was constructed and evaluated using a nomogram, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results The key variables identified by the model were tumor volume (P = 0.017), Eastern Cooperative Oncology Group performance status score (P = 0.035), 95% of the minimum dose to the target volume (P = 0.028), percentage of bilateral lung volume receiving 20 Gy of radiation (P < 0.001), and neutrophil-to-lymphocyte ratio (P = 0.021). The ROC curve showed that the areas under the curve (AUC) for the model in the training and validation groups were 0.987 and 0.992, respectively, indicating good predictive ability. The calibration curve and decision curve further confirmed the accuracy and clinical practicability of the model. Conclusion The predictive model proposed in this study can accurately assess the risk of developing RILI in patients with NSCLC who have undergone radiotherapy, demonstrating its potential value in clinical practice.

ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor （PDGF）/naked cuticle homolog 2 （NKD2） /Wnt signaling pathway in rats with chronic renal failure （CRF）. MethodsSixty male SD rats were randomly divided into normal group， model group， Niaoduqing group （5 g·kg^-1）， low-dose Shenshu Fujian decoction group （5.5 g·kg^-1）， medium-dose Shenshu Fujian decoction group （11 g·kg^-1）， and high-dose Shenshu Fujian decoction group （22 g·kg^-1）， with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling， intragastric administration was given once daily for 28 consecutive days. After treatment， the renal morphology of rats was observed. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect renal histopathological changes， and collagen volume fraction （CVF） was calculated. Serum levels of inflammatory markers interleukin （IL）-1β and IL-6 were measured using enzyme-linked immunosorbent assay （ELISA）. The expressions of fibronectin 1 （FN1）， type Ⅰ collagen （ColⅠ）， α-smooth muscle actin （α-SMA）， platelet-derived growth factor receptor-β （PDGFR-β）， NKD2， dishevelled protein 2 （DVL2） and β-catenin in renal tissue were detected by immunohistochemistry and Western blot. ResultsCompared with the normal group， the model group showed significant renal pathological changes， a markedly increased kidney weight/body weight ratio （P<0.01）， significantly elevated CVF （P<0.01）， and notably increased serum levels of SCr， BUN， IL-1β， and IL-6 （P<0.01）. Expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were also significantly increased （P<0.01）. Compared with the model group， all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF （P<0.01）， as well as markedly decreased serum SCr， BUN， IL-1β， and IL-6 levels. Protein expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were decreased， with more pronounced effects observed in the Niaoduqing， medium-dose， and high-dose Shenshu Fujian decoction groups （P<0.05， P<0.01）. ConclusionShenshu Fujian decoction improves renal function， reduces inflammation， and reverses renal fibrosis in CRF rats， possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.

Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H O ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H O . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na /K -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na /K -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

ObjectiveTo investigate the effects of Guizhi Jia Longgu Mulitang on the expression difference of interleukin-10 （IL-10） and tumor necrosis factor -α （TNF-α） in related organs of insomnia rats with sensory dysfunction dominated by lung and study the mechanism of Guizhi Jia Longgu Mulitang in improving insomnia. MethodSD rats were randomly divided into the blank group， model group， western medicine group， and traditional Chinese medicine （TCM） group， with 10 rats in each group. The rats were deprived of sleep by shallow water environment method in a long platform， and the modeling lasted for 42 d. The blank group and model group were given 0.05 mL·kg^-1 normal saline by gavage， and the western medicine group and TCM group were given drugs during modeling. To be specific， the western medicine group was given 0.105 mg·kg^-1 dexzopiclone tablet by gavage， while the TCM group was given 7 600 mg·kg^-1 Guizhi Jia Longgu Mulitang by gavage， both lasting for 28 days. After successful modeling， the Morris water maze experiment was performed on the 42nd day to detect the motion and spatial memory ability of rats. The levels of IL-10 and TNF-α in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-10 and TNF-α in the lung and brain tissue of rats was detected by Western blot. The levels of IL-10 and TNF-α in the lung and brain tissue of rats were detected by immunohistochemistry. ResultCompared with the blank group， the sleep stages non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) of the model group were significantly shortened （P<0.5， P<0.01）， and the wake stage was significantly increased （P<0.01）. The total time and distance of platform exploration were significantly increased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly decreased （P<0.01）. ELISA results showed that the serum IL-10 level was significantly decreased （P<0.01）， and TNF-α level was significantly increased （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain and lung tissue of rats was significantly decreased （P<0.01）， and the protein expression of TNF-α was significantly increased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in the brain and lung tissue of rats was significantly decreased （P<0.01）， and that of TNF-α was significantly increased （P<0.01）. Compared with the model group， the NREM stage and REM stage of the western medicine group and the TCM group were significantly increased （P<0.5， P<0.01）， and the wake stage was shortened （P<0.5）. The total time and distance of platform exploration were significantly decreased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly increased （P<0.05， P<0.01）. The serum IL-10 level was significantly increased （P<0.01）， and the serum TNF-α level was significantly decreased according to the ELISA results （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.01）， and the protein expression of TNF-α was significantly decreased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.05， P<0.01）， and the expression of TNF-α was significantly decreased （P<0.05， P<0.01）. ConclusionGuizhi Jia Longgu Mulitang can improve the expression of IL-10 and TNF-α in brain and lung tissue of insomnia rats with sensory dysfunction dominated by lung， prolong sleep time， and then improve insomnia. The mechanism may be related to improving the expression level of inflammatory factors.

Objective:To make an individual phantom that was printed by using three dimension(3D)technique,which could reflect the real situation of patient,and to analyze the computed tomography(CT)value and dose distribution of radiotherapy on each organ of the inside of the 3D-printed individual phantom.Methods:According to the localization of CT image of the patient,the empty shell of 3D structure of each organ were reconstructed and printed by using 3D technique.The CT value was used as basis to select the equivalent material of each organ to perform fill,which could obtain the individual phantom of chest that could appear the structural characteristics of patient.The treatment plan of patients were included in treatment plan group,and the plans which were transplanted to 3D-printed individual phantom from treatment plan of patients were included in phantom plan group.The dosimetric parameters of the plans of two groups were compared.Results:The average CT values of left and right lung,soft tissue,cancellous bone,compact bone and heart of the phantom plan group were respectively-709,-737,14,144,760 and 28 HU.The errors of the all CT values between phantom images and located images of patients were less than 16.7%.The exposure doses of normal tissues of radiotherapy plans on the images of two groups could meet the clinical requirements.The minimum dose(Dmin),mean dose(Dmean),the corresponding doses of 98%,50% and 2% target volumes(D98%,D50% and D2%),conformity index(CI),homogeneity index(HI),monitor unit(MU)of dosimetric parameters of the target region could meet the clinical requirements without statistically significant differences.There was significant differences in the maximum dose(Dmax)of the target region(t=2.678,P＜0.05).Among of these Dmax values,the Dmax value of phantom plan group was larger,which was(56.97±0.32)Gy.Conclusion:The CT value,tissue structure and spatial distribution of the phantom,which is finally designed,can emulate the chest of human body in radiotherapy.It has verified the feasibility that 3D-printed phantom is applied in measuring dose in the quality assurance of radiotherapy.

Objective To explore the mechanism of Yanggan Anhun Decoction in the treatment of insomnia with liver failing in storing soul type based on network pharmacological methods;To perform animal model validation.Methods The drug components and targets of Yanggan Anhun Decoction were retrieved from TCMSP and BATMAN-TCM databases,and the targets of insomnia with liver failure store soul type were retrieved from GeneCards,NCBI and DisGeNET databases.By constructing a protein-protein interaction(PPI)network and analyzing GO and KEGG pathway enrichment,the signaling pathway of Yanggan Anxin Decoction in treating insomnia with liver failing in storing soul type was determined,and molecular docking was performed between the main active components and core targets.24 SD rats were randomly divided into normal group,model group,TCM group and Western medicine group,with 6 rats in each group.The insomnia model rats with liver failing in storing soul type were constructed by compound multi factor stimulation method,and were given drugs for 14 days.The cognitive memory ability of rats were detected by Morris water maze test;Nissl staining was used to observe the morphology and number of Nissl bodies in the hypothalamus of rats;serum IL-6 and TNF-α contents were detected by ELISA;IL-6 and TNF-α in hypothalamus and Bcl-2,Bax protein expression levels of rats were detected by immunohistochemistry.The relative expressions of p38 MAPK,p-p38 MAPK,Bcl-2,Bax proteins in the hypothalamus of rats were detected by Western blot.Results A total of 301 active components,321 potential targets and 92 key targets were obtained.Key active components such as quercetin,kaempferol,luteolin,wogonin,sebiferic acid and β-sitosterol,as well as core targets such as MAPK,IL6 and TNF were obtained after screening.The key targets mainly focused on various signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,dopaminergic synapse,and neuroactive ligand-receptor interaction,etc.Kaempferol,quercetin,digitonin and other flavonoids had good binding activity and stability with MAPK,TNF,IL6 and showed good affinity.The results of animal experiments showed that,compared with the normal group,the cognitive memory ability of the model group decreased(P<0.05),Nissl bodies were stained shallowly,the density was lower,the cell body was shrunk and deformed,the cell nucleus was broken and dissolved,and the serum and hypothalamic IL-6,TNF-α increased(P<0.05),the expressions of p-p38 MAPK/p38 MAPK and Bax in hypothalamus increased(P<0.05),while the expressions of Bcl-2 and Bcl-2/Bax decreased(P<0.05);compared with the model group,the cognitive memory ability of the TCM group and the Western medicine group were improved,the number of Nissl bodies significantly increased,the nucleus was clear,the cell body shrinkage and deformation were improved(P<0.05),the levels of IL-6 and TNF-α in serum and hypothalamus decreased(P<0.05),while the expressions of p-p38 MAPK/p38 MAPK and Bax decreased,and the expression of Bcl-2 and Bcl-2/Bax increased(P<0.05).Conclusion Yanggan Anhun Decoction may play its effects in treating insomnia with liver failing in storing soul type by regulating MAPK,TNF,IL6,Bcl-2,Bax and other core targets,and interfering with p38MAPK signaling pathway.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

BACKGROUND: Lung cancer is the first leading cause of morbidity and mortality among the malignant tumors, which has become a hot issue in current research. Clinically, lung cancer is divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) according to the pathological types. NSCLC includes adenocarcinoma, squamous cell carcinoma and other types of lung cancer, accounting for about 80% of all lung cancer. Venous thromboembolism (VTE) includes deep venous thrombosis (DVT) and pulmonary embolism (PE), which is a recognized complication in lung cancer patients with higher morbidity and mortality. The aim of this study is to determine the incidence of DVT and reveal the risk factors for DVT in the postoperative patients with lung cancer. METHODS: We collected 83 postoperative patients with lung cancer admitted to the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital from December 2021 to December 2022. All these patients were examined by color Doppler ultrasound of lower extremity vein upon admission and after operation to analyze the incidence of DVT. In order to explore the possible risk factors for DVT in these patients, we further analyzed the correlations between DVT and their clinical features. At the same time, the changes of coagulation function and platelet were monitored to investigate the value of blood coagulation in the patients with DVT. RESULTS: DVT occurred in 25 patients after lung cancer operation, and the incidence rate of DVT was 30.1%. Further analysis found that the incidences of postoperative lower limb DVT were higher in lung cancer patients of stage III+IV or over 60 years of age (P=0.031, P=0.028). D-Dimer level in patients with thrombosis was significantly higher than that in non-thrombus patients on the 1st, the 3rd, and the 5th day after operation (P<0.05), and there was no significant difference in platelets and fibrinogen (FIB) (P>0.05). CONCLUSIONS The overall incidence of DVT in our center after lung cancer patients operation was 30.1%. Late-stage and older postpatients were more likely to develop DVT, and these patients with higher D-Dimer values should be considered the possibility of VTE events.
Humans ; Middle Aged ; Aged ; Lung Neoplasms/surgery* ; Incidence ; Carcinoma, Non-Small-Cell Lung ; Venous Thromboembolism ; Venous Thrombosis/etiology*

Objective To analyze the immunological effect and its influencing factors of HAART on HIV/AIDS with a baseline CD4 of less than 350 cells/mm³ in Hubei Province during 2011-2020. Methods The treatment information of people living with HIV/AIDS (PLWH) was collected through China Disease Control and Prevention Information System, and the change of CD4 mean value was analyzed by Wilcoxon sign rank sum test. Chi square test and multivariate logistic regression were used to analyze the factors influencing the immunological effect. Results The mean value of CD4 cell count at baseline was (172.78±107.65) cells/mm3 before treatment and (398.85±206.71) cells/mm³ in the fifth year after treatment. Patients with baseline CD4<50 /mm3 had the largest increase in CD4 mean value after treatment (P<0.05). Multivariate logistic regression analysis showed that Age ≥35 years, heterosexual transmission, time interval from diagnosis to treatment≥1 month, baseline CD4<50 /mm3, treatment time 7-<18 months, and drug failure were the risk factors for the success of antiviral therapy(P<0.05). Conclusion The immunological effect of HIV/AIDS antiviral therapy in Hubei Province is affected by many factors. It is necessary to strengthen the implementation of early detection and early treatment strategy and promote treatment compliance education for patients aged ≥35 years.