Objective To investigate the expression levels of FOXO1 and SMAD4 in esophageal cancer (EC) tissues and their associations with clinicopathological features and prognosis. Methods Tissue samples of cancerous and adjacent non-cancerous tissues were collected from 131 EC patients. Hematoxylin-eosin (HE) staining was performed to observe the pathological morphology of EC and adjacent tissues. The mRNA expression of FOXO1 and SMAD4 was measured using quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of FOXO1 and SMAD4 was determined by immunohistochemistry; Spearman's correlation analysis was employed to assess the correlation between FOXO1 and SMAD4 protein expression in EC tissues; Cox regression analysis was conducted to analyze factors influencing the prognosis of EC patients; Kaplan-Meier analysis was used to perform survival analysis for EC patients. Results The expression of FOXO1 mRNA and its protein positive expression rate were significantly higher in the EC tissues than those in the adjacent tissues, whereas the expression of SMAD4 mRNA and its protein positive expression rate were significantly lower (P < 0.05). FOXO1 and SMAD4 were associated with tumor diameter, tumor differentiation, lymph node metastasis and TNM stage (P < 0.05). A negative correlation was observed between FOXO1 and SMAD4 protein expression in EC tissues (r=-0.419, P < 0.05). FOXO1, SMAD4, tumor diameter, differentiation, lymph node metastasis and TNM stage were identified as factors influencing mortality in EC patients (P < 0.05). The 3-year overall survival rate of EC patients was 84.73% (111/131). The 3-year cumulative survival rate was significantly lower in the EC patients with positive FOXO1 expression than in thosewith negative FOXO1 expression (P < 0.05), while it was significantly higher in patients with positive SMAD4 expression than in those with negative SMAD4 expression (P < 0.05). Conclusion The positive expression rate of FOXO1 is higher, while that of SMAD4 is lower in EC tissues. Their protein expressions were associated with clinicopathological features and prognosis in EC patients. FOXO1 and SMAD4 may serve as important biomarkers for predicting the prognosis of EC.

Objective:To explore the early effects and safety of using a hybrid fixation strategy with 3D-printed porous tantalum metal augments to reconstruct substantial bone defects in complex primary total knee arthroplasty (TKA).Methods:A retrospective analysis was performed on the clinical data from August 2019 to September 2023, encompassing 20 patients (21 knees) with significant bone loss who underwent hybrid fixation with 3D-printed porous tantalum augments. The procedures were conducted at two medical centers: the First Affiliated Hospital, School of Medicine, Zhejiang University (11 cases) and Xiangya Hospital of Central South University (9 cases). The study cohort comprised 6 males (6 knees) and 14 females (15 knees), with a mean age of 61.05±11.23 years (range, 42-80 years). The distribution of cases was 7 on the left side and 14 on the right side. All cases were categorized as type 3 according to the Anderson Orthopaedic Research Institute (AORI) classification system. The cohort included 19 unilateral and 1 bilateral case, with 5 involving complex primary replacements (3 with Charcot arthropathy, 1 with syphilitic arthropathy, and 1 with severe valgus deformity) and 16 revision surgeries (13 for aseptic loosening and 3 for infection). Preoperative assessments included routine CT scans and digital three-dimensional reconstructions to identify large metaphyseal defects exceeding 50% of the metaphyseal area or those thicker than 10 mm. For such defects, 3D-printed standardized porous tantalum augments were implemented. In cases of extensive cavitary bone defects or severe metaphyseal defects where the medial and lateral defects collectively exceeded 80% of the metaphyseal region or where the residual bone stock was insufficient for screw fixation of standardized augments, 3D-printed personalized custom-made porous tantalum augments were employed for hybrid fixation and repair. Comparative analyses were conducted on pre- and postoperative imaging data (prosthesis positioning and complications), knee range of motion (ROM), visual analogue scale (VAS) for pain, and Knee Society score (KSS).Results:Of the cases, 17 were repaired using standardized 3D-printed porous tantalum augments, while 4 underwent repairs with customized augments for hybrid fixation. Follow-up averaged 26.5±15.0 months (range, 12-62 months). There was a significant increase in knee ROM, improving from 72.8°±31.9° preoperatively to 113.2°±6.8° at 12 months postoperatively ( P<0.05). VAS scores decreased from 6.6±1.4 preoperatively to 2.5±1.0 at 12 months postoperatively ( P<0.05). Similarly, KSS improved from 52.8±6.4 preoperatively to 80.7±7.9 at 12 months postoperatively ( P<0.05). There were no incidences of prosthesis displacement, poor bone integration, or postoperative infections. Conclusion:The hybrid fixation strategy employing 3D-printed porous tantalum augments has been found to be effective in addressing significant bone defects in TKA. The follow-up results indicate a satisfactory biological integration of the porous tantalum metal augments with the host bone, which has resulted in substantial improvements in pain relief and knee joint functionality.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Objective:To study the effects of docetaxel, cisplatin and fluorouracil (TPF) regimen simultaneous intensity modulated radiotherapy (IMRT) on immune function and survival prognosis of patients with advanced esophageal cancer.Methods:A total of 93 patients with advanced esophageal cancer were screened in Hebei Veterans General Hospital from June 2015 to December 2017, and were divided into two groups using randomized envelope method. The observation group (47 cases) was given synchronous TPF regimen and IMRT, and the control group (46 cases) was given synchronous PF regimen (cisplatin combined with fluorouracil) and IMRT. Esophageal barium meal, chest and upper abdominal CT were reviewed within 1 month after treatment to assess the short-term efficacy and compare the immune function of the two groups before and after treatment. Kaplan-Meier survival curve was plotted to evaluate the long-term efficacy based on overall survival (OS). The incidence of adverse reactions in the two groups was collected to evaluate their safety.Results:After treatment, the T cell subgroup CD8 + level of the observation group was higher than that of the control group [(33.55±4.46)% vs. (29.06±3.61)%, P<0.05], while CD3 + [(51.29±5.22)% vs. (56.04±6.10)%, P<0.05], CD4 + [(28.27±3.63)% vs. (30.35±3.52)%, P<0.05] and CD4 + /CD8 + (0.84±0.25 vs. 1.04±0.08, P<0.05) levels were lower than those of the control group. The effective rate of recent treatment in the observation group was 82.98% (39/47), while the effective rate in the control group was only 63.04% (29/46), with a statistically significant difference ( χ2=4.70, P=0.030). The median OS of the observation group was 25.3 months (95% CI: 17.9-26.1), and that of the control group was 18.2 months (95% CI: 14.4-25.5), with a statistically significant difference ( χ2=3.28, P=0.038). Adverse reactions during the follow-up period of the two groups of patients were mainly nausea/vomiting, fatigue, anorexia, hematological toxicity, esophagitis and pneumonia, etc., which were mostly grade 1-2, and disappeared after symptomatic treatment or termination of treatment. Compared with the control group, the incidence of nausea/vomiting (46.81% vs. 78.26%, χ2=9.80, P=0.002), anorexia (44.86% vs. 71.74%, χ2=6.99, P=0.008), leukopenia (36.96% vs. 73.91%, χ2=13.37, P<0.001) and esophagitis (61.70% vs. 82.61%, χ2=5.05, P=0.025) adverse reactions was lower in the observation group. Conclusion:TPF combined with IMRT has high efficacy and low adverse reactions, which can be used as an effective treatment to improve the survival prognosis of patients with advanced esophageal cancer.

Objective: To investigate the effect of glucocorticoid (GC) to cortisol-binding globulin (CBG) expression in rats and the correlation between the changes of CBG levels and the osteonecrosis of the femoral head (ONFH) in rats after GC treatment. Methods: A total of 72 healthy adult SD rats were randomly divided into low-dose group and high-dose group by computer random grouping.Thirty-six rats of low-dose group were injected dexamethasone at a dose of 1.5 mg·kg^-1·d^-1.Thirty-six rats of high-dose group were injected dexamethasone at a dose of 3.0 mg·kg^-1·d^-1.The blood samples were regularly collected, CBG levels in blood samples were detected by Western-blotting.Rats were killed in batches, femoral head was collected and observed under light microscope after HE staining.The bone lacuna of each group was compared and the ratio of empty lacuna was calculated.Finally, the correlation between the change of CBG level and ONFH was evaluated. Results: On the first day after administration, the CBG level of the two groups decreased, and reached the lowest level on the seventh day of administration, and then gradually increased.The reduction of CBG level in the high dose group was greater.With the increase of time after treatment, the number and rate of bone lacuna void in the two groups increased gradually.28 days after treatment, the number of empty bone lacunae and the rate of empty bone lacunae in the low dose group were (6.75±0.42) and (13.98±2.19)%, respectively, which were lower than those in the high dose group[(11.03±0.62) and (21.99±3.17)%, t=4.864, 3.926, all P<0.05]. Conclusion The risk of ONFH is increased with the increase of the dose of dexamethasone, and there was no significant difference between the sexes.The decrease of serum CBG level after medication is correlated with the occurrence of ONFH.