Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

Objective To investigate the impact of serine/threonine-protein kinase 1(AKT1)-mediated autophagy in hepatocellular carcinoma(HCC)cells on their sensitivity to 125I seed irradiation.Methods ① iProX database and STRING12.0 website were utilized to analyze the proteomic data of HCC before and after 125I seed irradiation to explore the differentially expressed proteins and associated functional connections.Meanwhile,The Cancer Genomics Atlas(TCGA)database was employed to analyze the relationship between AKT1 expression level and the survival of HCC patients.② Human HCC cell lines HUH7 and Hep3B were exposed to continuous irradiation from 125I radioactive seeds with an initial apparent activity of 0.8 mCi per seed for approximately 120 h,accumulating a total dose of 8 Gy,while the control cells were cultured under normal condition for 120 h.③ Autophagy inhibitor,chloroquine(CQ)and inducer,rapamycin(RAPA)were used to treat the HCC cells respectively to establish the CQ group and the RAPA group.The lentiviral transfection technique was employed to construct the HCC cells with overexpressed AKT1,namely the AKT1 group.The HCC cells treated in the same way were continuously irradiated with 125I seeds for 120 h to construct the CQ+125I group,the RAPA+125I group,and the AKT1+125I group.④The changes in microtubule-associated protein light chain 3(LC3),p62,AKT1 and p-AKT1 were detected by Western blotting.Cell immunofluorescence assay was employed to observe the expression of autophagy related proteins,such as LC3.The colony forming ability and apoptotic rate were detected with plate cloning assay and flow cytometry.Results ① Continuous irradiation with 125I seeds resulted in decreased expression of p62 and increased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.05)when compared with the negative control(NC)group.Immunofluorescence assay revealed more green fluorescence spots of LC3.When compared with the 125I group,the CQ+125I group had significantly increased expression of p62(P＜0.01),decreased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.01),lower apoptotic rate(P＜0.01),and more colony formations(P＜0.01).In contrast,the results in the RAPA+125I group were opposite to those of the CQ+125I group.② Analysis on the iProX database showed that the expression of AKT1 was decreased in the irradiated group,and analysis on the TCGA database indicated that high expression of AKT1 predicted a poor prognosis for HCC patients(P＜0.01).③After irradiation with 125I seeds,the expression of AKT1 at both the RNA and protein levels was decreased in the 125I group(P＜0.01).After overexpression of AKT1,the level of autophagy was decreased(P＜0.05).Irradiation of HCC cells with overexpressed AKT1 using 125I seeds could partially restore the level of autophagy.In the AKT1+125I group,the expression of AKT1,pAKT1 and p62 were all decreased,and the ratio of LC3Ⅱ/LC3Ⅰwas increased than the AKT1 group(P＜0.05).④ The apoptotic rate of the AKT1+125I group was lower than that of the 125I group(P＜0.05)and higher than that in the AKT1 group(P＜0.05).In HUH7 cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group(P＜0.05).In Hep3B cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group,and the clonogenic ability of the AKT1 group was higher than that of the NC group(P＜0.05).Conclusion 125I seed irradiation induce lethal autophagy in HCC cells by reducing the expression of AKT1,providing a new theoretical basis for the implantation of 125I radioactive seeds in the treatment of HCC.

Objective:To explore the effects and potential mechanisms of cell growth regulator 1 ( CGREF1) with an EF hand domain in colorectal cancer proliferation and migration. Methods:Fifty paraffin specimens of colorectal cancer tissues and corresponding paracancerous tissues were selected from January 2023 to January 2024 from the Northern Jiangsu People's Hospital Affiliated to Yangzhou University for analysis, and TCGA, GDSC, KMPLOT and STRING databases were used to explore the expression, prognosis, immune microenvironment, drug sensitivity and related signaling pathway functions of CGREF1 in colorectal cancer. Tissue and cellular expression levels of CGREF1 were analyzed by immunohistochemistry and qRT-PCR. Lentiviral-mediated CGREF1 overexpression in SW-620 cells (OE- CGREF1 vs NC groups) was functionally characterized through CCK-8 proliferation assays, colony formation tests, and scratch wound healing migration assays, with mechanistic investigation via Western blot analysis of apoptosis markers, invasion-related proteins, and RAS/RAF/ERK pathway components. In vivo tumorigenicity was assessed by subcutaneous injection of control or CGREF1-overexpressing SW620 cells in nude mice ( n=3 per group) with tumor growth monitoring. Software of GraphPad Prism 9 was used for statistical analysis of experimental data. Results:CGREF1CGREF1RASERK Studies based on databases, clinical samples and colorectal cancer cell line analyses demonstrated that CGREF1 is downregulated in colorectal cancer, where low CGREF1 expression showed positive correlation with tumor diameter and invasion depth. CGREF1 is closely related to tumor immune infiltration microenvironment and sensitivity to multiple anti-tumor drugs. Overexpression of CGREF1 promoted cell apoptosis while inhibiting cell proliferation, invasion and migration. Overexpression of CGREF1 downregulated the expression levels of RAS, ERK and P-P38/MAPK pathway proteins. CGREF1 inhibited tumor growth in vivo. Conclusion:CGREF1 can inhibit the proliferation, colony formation, and migration of CRC cells through the RAS/ERK/MAPK pathway.

Objective:To translate the Creature of Habit Scale(COHS)into Chinese version and test its va-lidity and reliability in community adults.Methods:A total of 474 adult participants(Sample 1)were recruited through social media platforms for item analysis and exploratory factor analysis.Additionally,4 102 community a-dults(Sample 2)were recruited for confirmatory factor analysis,criterion validity,and internal consistency reliabili-ty testing.Four weeks later,235 participants were randomly selected from Sample 1 for a retest.The State-Trait Anxiety Inventory-Trait Questionnaire(STAI-T),Obsessive-Compulsive Inventory-Revised(OCI-R),and Brief Barratt Impulsiveness Scale(BBIS)were used as criterion questionnaires.Results:The Chinese version of the COHS contained 23 items,grouped into two factors,namely regularity and automaticity.The item loadings ranged from 0.40 to 0.89,with the two-factor model cumulatively explaining 56.7％of the total variance.Confirmatory factor analysis indicated a good model fit(x2/df=2.17,CFI=0.86,TLI=0.85,RMSEA=0.07,SRMR=0.06).The total COHS scores were positively correlated with the STAI-T and OCI-R scores(r=0.32,0.50;Ps＜0.01),and the automaticity factor scores were positively correlated with the BBIS scores(r=0.30,P＜0.01).The Cron-bach's α coefficient for the total scale was 0.89,and the test-retest reliability was 0.87.Conclusion:The Chinese version of the Creature of Habit Scale is a reliable and valid tool for measuring habitual behaviors in community a-dults.

Objective:To evaluate the therapeutic value of radiotherapy in combined immunotherapy and chemotherapy as first-line treatment for patients with oligometastatic non-small cell lung cancer (NSCLC).Methods:A retrospective analysis was conducted on data from 195 NSCLC patients who lacked epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and were treated at the Anyang Tumor Hospital and the Fourth Hospital of Hebei Medical University from January 2019 to December 2021. These patients consisted of 166 male and 29 female cases, aged from 28 to 85 years, with an average age of (61.4 ± 9.3) years. These patients were divided into two groups, with each group receiving the radiotherapy and combined immunotherapy and chemotherapy (the radiotherapy and combination group, n = 60) and combined immunotherapy and chemotherapy only (the combination group, n = 135). Then, propensity score matching (PSM) was performed to analyze the differences in prognosis between both groups before and after PSM, as well as the short-term efficacy and adverse reactions after PSM. Results:For the 195 NSCLC patients, the median follow-up time was 31.8 months, with median overall survival (OS) and median progression-free survival (PFS) recorded at 23.8 months and 9.2 months, respectively. The radiotherapy and combination group exhibited enhanced 1-, 2-, and 3-year survival rates of 78.5%, 55.9%, and 45.1%, respectively, significantly higher than the combination group (48.3%, 35.6%, and 26.6%, respectively, χ2 = 14.65, P < 0.001). Similarly, the radiotherapy and combination group displayed 1-, 2-, and 3-year PFS rates of 51.9%, 29.5%, and 22.7%, respectively, exceeding those of the combination group (30.0%, 24.5%, and 16.9%, respectively, χ2=6.09, P=0.014). After PSM, the radiotherapy and combination group manifested an objective response rate (ORR) of 60.0% (33/55) and a disease control rate (DCR) of 89.1% (49/55), which were 16.4% (9/55) and 56.4% (31/55), respectively for the combination group. These results suggested that the radiotherapy and combination group demonstrated significantly higher ORR and DCR ( χ2 = 22.18, 14.85, P<0.001). After PSM, the radiotherapy and combination group yielded 1-, 2-, and 3-year survival rates of 70.9%, 52.3%, and 41.9%, respectively, significantly than the combination group (43.6%, 29.8%, and 27.1%, respectively, χ2=8.95, P=0.003). The radiotherapy and combination group exhibited 1-, 2-, and 3-year PFS rates of 47.3%, 27.3%, and 18.7%, respectively, significantly higher than the combination group (23.6%, 17.6%, and 15.4%, respectively, χ2 = 6.71, P = 0.010). Multivariate Cox regression analysis revealed that independent factors affecting OS included clinical stage, treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.88, 2.11, 0.23, 1.79, P < 0.05). Similarly, independent factors affecting PFS consisted of treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.62, 0.37, 3.42, P <0.05). There were no statistical differences in the incidence of grade ≥ 2 bone marrow suppression (18.2% vs. 12.7%) and grade ≥ 2 pneumonia (21.8% vs. 14.5%) between both groups ( P>0.05). Conclusions:Introducing radiotherapy into combined immunotherapy and chemotherapy as first-line treatment for oligometastatic NSCLC can optimize both local and systemic disease control and significantly improve patient prognosis without increasing treatment-related adverse reactions.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective:To investigate the bone augmentation effects of domestic decellularized porcine small intestinal submucosa (PSIS) absorbable biomembrane and domestic bovine pericardium tissue (BPT) absorbable biomembrane in guided bone regeneration (GBR) for single-tooth implantation in diabetic patients.Methods:A prospective case-control study was conducted with 48 diabetic patients who received single-tooth implant restoration at the Department of Prosthodontics, School of Stomatology. The Fourth Military Medical University, between January 2023 and January 2024. Patients were randomly assigned to the study group (PSIS group) and the control group (BPT group) using a random number table, with 24 patients in each group. GBR was performed simultaneously with the implant surgery. Cone-beam CT was used to compare the buccal-side horizontal bone gain at 6 months post-operation between the two groups. Wound healing was evaluated at 1 and 4 weeks post-operation using wound healing scores.Results:At 6 months post-operation, the buccal-side horizontal bone gain at 2 mm below the implant abutment in the study group [69.1 (55.2, 82.4) mm] and the control group [71.4 (59.8, 77.0) mm] showed no statistically significant difference ( Z=-0.25, P=0.805). The wound healing scores at 1 and 4 weeks post-operation in the study group did not differ significantly from those in the control group at the same time points (1 week: Z=-0.49, P=0.627; 4 weeks: Z=-0.61, P=0.539). Conclusions:The use of two types of domestic absorbable collagen membranes for GBR in single-tooth implantation in diabetic patients showed comparable buccal-side horizontal bone gain effects at 6 months post-operation and similar clinical outcomes for wound healing at 1 and 4 weeks post-operation in both groups. The GBR effects of PSIS and BPT are similar.

Objective:To evaluate the therapeutic value of radiotherapy in combined immunotherapy and chemotherapy as first-line treatment for patients with oligometastatic non-small cell lung cancer (NSCLC).Methods:A retrospective analysis was conducted on data from 195 NSCLC patients who lacked epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and were treated at the Anyang Tumor Hospital and the Fourth Hospital of Hebei Medical University from January 2019 to December 2021. These patients consisted of 166 male and 29 female cases, aged from 28 to 85 years, with an average age of (61.4 ± 9.3) years. These patients were divided into two groups, with each group receiving the radiotherapy and combined immunotherapy and chemotherapy (the radiotherapy and combination group, n = 60) and combined immunotherapy and chemotherapy only (the combination group, n = 135). Then, propensity score matching (PSM) was performed to analyze the differences in prognosis between both groups before and after PSM, as well as the short-term efficacy and adverse reactions after PSM. Results:For the 195 NSCLC patients, the median follow-up time was 31.8 months, with median overall survival (OS) and median progression-free survival (PFS) recorded at 23.8 months and 9.2 months, respectively. The radiotherapy and combination group exhibited enhanced 1-, 2-, and 3-year survival rates of 78.5%, 55.9%, and 45.1%, respectively, significantly higher than the combination group (48.3%, 35.6%, and 26.6%, respectively, χ2 = 14.65, P < 0.001). Similarly, the radiotherapy and combination group displayed 1-, 2-, and 3-year PFS rates of 51.9%, 29.5%, and 22.7%, respectively, exceeding those of the combination group (30.0%, 24.5%, and 16.9%, respectively, χ2=6.09, P=0.014). After PSM, the radiotherapy and combination group manifested an objective response rate (ORR) of 60.0% (33/55) and a disease control rate (DCR) of 89.1% (49/55), which were 16.4% (9/55) and 56.4% (31/55), respectively for the combination group. These results suggested that the radiotherapy and combination group demonstrated significantly higher ORR and DCR ( χ2 = 22.18, 14.85, P<0.001). After PSM, the radiotherapy and combination group yielded 1-, 2-, and 3-year survival rates of 70.9%, 52.3%, and 41.9%, respectively, significantly than the combination group (43.6%, 29.8%, and 27.1%, respectively, χ2=8.95, P=0.003). The radiotherapy and combination group exhibited 1-, 2-, and 3-year PFS rates of 47.3%, 27.3%, and 18.7%, respectively, significantly higher than the combination group (23.6%, 17.6%, and 15.4%, respectively, χ2 = 6.71, P = 0.010). Multivariate Cox regression analysis revealed that independent factors affecting OS included clinical stage, treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.88, 2.11, 0.23, 1.79, P < 0.05). Similarly, independent factors affecting PFS consisted of treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.62, 0.37, 3.42, P <0.05). There were no statistical differences in the incidence of grade ≥ 2 bone marrow suppression (18.2% vs. 12.7%) and grade ≥ 2 pneumonia (21.8% vs. 14.5%) between both groups ( P>0.05). Conclusions:Introducing radiotherapy into combined immunotherapy and chemotherapy as first-line treatment for oligometastatic NSCLC can optimize both local and systemic disease control and significantly improve patient prognosis without increasing treatment-related adverse reactions.

Objectives:To investigate the coccygeal morphology in adult Chinese without coccydynia using CT scans,and to provide a morphological reference for assessing the risk of coccydynia in Chinese popula-tion.Methods:A retrospective analysis was conducted on 113 patients without coccydynia who underwent pelvic three-dimensional CT scans at the Second Affiliated Hospital of Wenzhou Medical University between August 2018 and August 2023.There were 67 males and 46 females,with a mean age of 53.5±19.1 years(range:18-93 years).The morphological characteristics of the sacrococcygeal anatomical structures,including coccyx number,coccyx type(modified Nathan classification),sacrococcygeal joint fusion,intercoccygeal joint subluxation,coccygeal sacralization,lateral deviation of coccygeal tip,ventral angulation of S5,and coccygeal bony spicule,were analyzed on the three-dimensional reconstructed CT images;And relevant morphological parameters were measured,such as the coccygeal straight length,sacral straight length,sacrococcygeal straight length,sacrolumbar angle,sacrococcygeal angle,sacrococcygeal joint angle,intercoccygeal angle,and first in-tercoccygeal joint angle,with consistency tests conducted for the measurements.The differences in morpholog-ical parameters were compared between different genders and age groups(＜50 years and ≥50 years).Results:Among the 113 asymptomatic adult Chinese subjects,88 cases(77.9％)had a 4-segment coccyx,and type Ⅰcoccyx(modified Nathan classification)was the most common type(53 cases),accounting for approximately 46.9％.The incidence of sacrococcygeal joint fusion,intercoccygeal joint subluxation,coccygeal sacralization,lateral deviation of the coccygeal tip,ventral angulation of S5,and coccygeal bony spicule were 52.2％(59 cases),25.7％(29 cases),20.4％(23 cases),53.1％(60 cases),7.1％(8 cases),and 15.0％(17 cases),respectively.The consistency test showed that the consistency of the measurement data among observers was good.In Chi-nese population,the coccygeal straight length was 3.59±0.72cm,sacral straight length was 10.97±0.92cm,and sacrococcygeal straight length was 12.68(11.99,13.69)cm.The lumbosacral angle,sacrococcygeal angle,inter-coccygeal angle,and first intercoccygeal joint angle were 38.0°±7.3°,110.6°±10.6°,173.1°(164.2°,178.2°),131.5°±21.5°,and 152.8°±17.1°,respectively.Gender comparisons showed that males had greater sacrococ-cygeal straight length and sacrococcygeal angle than females(P＜0.05).Age group comparisons revealed that subjects＜50 years had shorter coccygeal straight length,smaller lumbosacral angle,sacrococcygeal joint angle,and first intercoccygeal joint angle than those ≥50 years(P＜0.05),while the sacral straight length was longer in the＜50 years group(P＜0.01).Conclusions:Among the adult Chinese without coccydynia,4 coccygeal seg-ments and type Ⅰ(modified Nathan classification)are the most common.Sacrococcygeal joint fusion,coccygeal bony spicules,intercoccygeal joint subluxation,and coccygeal sacralization have relatively high incidences.Males have longer and straighter sacrococcygeal structures than females.Compared with those ≥50 years,subjects＜50 years have shorter coccyxes,longer sacra,and smaller lumbosacral angles.