AIM:To explore the relationship be-tween the level of myeloid-derived suppressor cell(MDSC)infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC).METHODS:A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024.Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration,dividing the patients into high-in-filtration group(MDSC≥2)and low-infiltration group(MDSC＜2).The objective response rate(iORR),disease control rate(iDCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves,and Cox regression analysis was applied to identify factors influencing prognosis.RESULTS:Among the 92 patients,53 were in the low MDSC infiltration group,and 39 were in the high MDSC infiltration group.The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group.The objective response rate(iORR)was 77.3％in the low MDSC infiltration group,higher than the 56.4％in the high MDSC in-filtration group(P=0.033).The disease control rate(iDCR)was 94.3％,also significantly higher than the 66.7％in the high MDSC infiltration group(P=0.001).Moreover,the median progression-free sur-vival(PFS)and overall survival(OS)in the low MD-SC infiltration group were 16.9 months and 27.6 months,respectively,which were significantly lon-ger than those in the high MDSC infiltration group(PFS 12.6 months,OS 22.3 months).Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group.Cox univariate analysis showed that smoking,PD-L1 ex-pression levels,tumor stage,and MDSC infiltration level were closely associated with PFS and OS.Mul-tivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS(HR=2.678,P=0.013)and OS(HR=2.254,P=0.022).CONCLUSION:The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor com-bined with chemotherapy in NSCLC patients.High MDSC infiltration suggests reduced treatment sen-sitivity and poor prognosis.MDSC infiltration level may serve as a predictive biomarker for the effica-cy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

AIM:To explore the relationship be-tween the level of myeloid-derived suppressor cell(MDSC)infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC).METHODS:A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024.Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration,dividing the patients into high-in-filtration group(MDSC≥2)and low-infiltration group(MDSC＜2).The objective response rate(iORR),disease control rate(iDCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves,and Cox regression analysis was applied to identify factors influencing prognosis.RESULTS:Among the 92 patients,53 were in the low MDSC infiltration group,and 39 were in the high MDSC infiltration group.The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group.The objective response rate(iORR)was 77.3％in the low MDSC infiltration group,higher than the 56.4％in the high MDSC in-filtration group(P=0.033).The disease control rate(iDCR)was 94.3％,also significantly higher than the 66.7％in the high MDSC infiltration group(P=0.001).Moreover,the median progression-free sur-vival(PFS)and overall survival(OS)in the low MD-SC infiltration group were 16.9 months and 27.6 months,respectively,which were significantly lon-ger than those in the high MDSC infiltration group(PFS 12.6 months,OS 22.3 months).Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group.Cox univariate analysis showed that smoking,PD-L1 ex-pression levels,tumor stage,and MDSC infiltration level were closely associated with PFS and OS.Mul-tivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS(HR=2.678,P=0.013)and OS(HR=2.254,P=0.022).CONCLUSION:The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor com-bined with chemotherapy in NSCLC patients.High MDSC infiltration suggests reduced treatment sen-sitivity and poor prognosis.MDSC infiltration level may serve as a predictive biomarker for the effica-cy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Objective To explore the effect of virtual reality treadmill training on balance and gait in stroke patients. Methods From March,2022,to March,2023,40 stroke patients in Beijing Tiantan Hospital,Capital Medical University were randomly divided into control group(n = 20)and experimental group(n = 20).Both groups received rou-tine rehabilitation training.The control group received ordinary treadmill walking training,and the experimental group received treadmill walking training with virtual reality,for two weeks.They were assessed with Berg Bal-ance Scale(BBS)and Timed Up and Go Test(TUGT),and the envelope ellipse area,center of pressure(COP)av-erage speed of movement,step length,stride length and stride width were compared between two groups before and after treatment. Results After treatment,the scores of BBS and time of TUGT improved in both groups(|t|>3.508,P<0.01),and they were better in the experimental group than in the control group(|t|>3.019,P<0.01);there was no significant dif-ference in the envelope ellipse area,COP average speed,and stride width between two groups(P>0.05);howev-er,the step length and stride width improved in the experimental group(|t|>4.008,P<0.01). Conclusion Treadmill training with virtual reality can improve the balance and walking ability of stroke patients.

Objective To observe the abnormal brain activity in patients with migraine without aura(MwoA)with MRI.Methods Fifty MwoA patients(MwoA group)and 46 healthy volunteers(control group)were prospectively enrolled.Functional MRI(fMRI)was performed to observe the dynamic regional homogeneity(dReHo)of brain regions,then brain regions with differences of dReHo value between groups were extracted,and correlations with clinical scales were analyzed.Results Compared with control group,dReHo values of surrounding cortex of bilateral calcarine fissure and right middle occipital gyrus increased,of right middle temporal gyrus,right middle frontal gyrus and left cuneus decreased in MwoA group(GRF correction,voxel level all P＜0.005,cluster level all P＜0.05).The weight analysis showed that brain regions with top 3 absolute weight values were surrounding cortex of right calcarine fissure,left cuneus and right middle occipital gyrus.dReHo value of surrounding cortex of left calcarine fissure in MwoA patients was negative correlated with self-rating depression scale(SDS)(r=-0.28,P=0.04).Conclusion Abnormalities in the upward transmission pathway of visual information existed in MwoA patient,especially in surrounding cortex of right calcarine fissure,left cuneus and right middle occipital gyrus.

Timely restoration of blood supply after myocardial infarction is crucial for saving the infarcted myocardi-um.So far,the most effective method is to restore myocardial oxygenation and coronary blood flow through coronary inter-ventional therapy.However,reperfusion may also lead to greater heart damage due to the reintroduction of molecular oxy-gen.New treatments are needed to protect the heart from myocardial ischemia-reperfusion injury(MIRI)to improve clini-cal outcomes in patients with acute myocardial infarction and heart failure(HF).A deeper understanding of the mecha-nisms of MIRI and the search for new treatments could provide key evidence to mitigate myocardial damage and improve pa-tient survival.At present,it has been found that copper,as a trace element in human body,can have a significant pro-tective effect on MIRI.Copper can reduce apoptosis in cardiomyocytes,that is,control the self-destruction process of cell,so as to reduce the degree of myocardial injury.However,the potential relationship between abnormal copper ion metabolism as well as cuproptosis and MIRI as well as HF has not been explored.In this review,we focus on potential therapeutic strategies for MIRI and understand the metabolic pathways of copper in the human body,so as to provide more options and hope for the treatment of cardiovascular diseases.

Timely restoration of blood supply after myocardial infarction is crucial for saving the infarcted myocardi-um.So far,the most effective method is to restore myocardial oxygenation and coronary blood flow through coronary inter-ventional therapy.However,reperfusion may also lead to greater heart damage due to the reintroduction of molecular oxy-gen.New treatments are needed to protect the heart from myocardial ischemia-reperfusion injury(MIRI)to improve clini-cal outcomes in patients with acute myocardial infarction and heart failure(HF).A deeper understanding of the mecha-nisms of MIRI and the search for new treatments could provide key evidence to mitigate myocardial damage and improve pa-tient survival.At present,it has been found that copper,as a trace element in human body,can have a significant pro-tective effect on MIRI.Copper can reduce apoptosis in cardiomyocytes,that is,control the self-destruction process of cell,so as to reduce the degree of myocardial injury.However,the potential relationship between abnormal copper ion metabolism as well as cuproptosis and MIRI as well as HF has not been explored.In this review,we focus on potential therapeutic strategies for MIRI and understand the metabolic pathways of copper in the human body,so as to provide more options and hope for the treatment of cardiovascular diseases.

Osteosarcoma (OS) is the most common primary malignant bone tumor that more commonly occurs in children and adolescents. The most commonly used treatment for OS is surgery combined with chemotherapy, but the treatment outcomes are typically unsatisfactory. High rates of metastasis and post-treatment recurrence rates are major challenges in the treatment of OS. This underlines the need for studying the in-depth characterization of the pathogenetic mechanisms of OS and development of more effective therapeutic modalities. Previous studies have demonstrated the important role of the bone microenvironment and the regulation of signaling pathways in the occurrence and development of OS. In this review, we discussed the available evidence pertaining to the mechanisms of OS development and identified therapeutic targets for OS. We also summarized the available treatment modalities for OS and identified future priorities for therapeutics research.
Child ; Adolescent ; Humans ; Bone Neoplasms/drug therapy* ; Signal Transduction ; Bone and Bones/metabolism* ; Treatment Outcome ; Osteosarcoma/drug therapy* ; Tumor Microenvironment

Objective:To characterize the injury to the ipsilateral ankle joint after low energy spiral fracture of the distal tibia.Methods:A retrospective study was conducted to analyze the 80 patients with distal tibial spiral fracture who had been treated at Department of Traumatic Orthopedics, Affiliated Hospital of Jining Medical University from March 2010 to March 2021. There were 61 males and 19 females with an age of (43.5±12.5) years. Their mean follow-up time was 67.0 (38.5, 90.0) months. All patients underwent preoperative X-ray examination, 64 ones preoperative CT examination, and 30 ones preoperative MRI examination. Of the 80 patients, 3 received conservative treatment with plaster external fixation, 3 closed reduction and intramedullary nail fixation, and 74 plate fixation. Statistically analyzed were incidence of posterior malleolus fracture, characteristics of posterior malleolus fracture lines, normal matching rate of the ipsilateral ankle joint, positive rate of intraoperative Cotton test or stress external rotation test of ipsilateral ankle joint, positive rates of passive pronation-external rotation and supination-external rotation stress tests during follow-up, incidences of short-term ankle pain (≤2 years) and medium-long term pain (>2 years) after operation, injuries to the anterior inferior tibiofibular ligament, the deep medial malleolus deltoid ligament and the posterior malleolus, and incidence of ankle injury.Results:The diagnostic rate for posterior malleolus fracture was 16.3% (13/80) on X-ray film, 60.9% (39/64) on CT and 76.7% (23/30) on MRI. 74.5% (35/47) of the posterior malleolus fracture lines opened on the lateral side. The normal matching rate of the ipsilateral ankle joint was 96.3% (77/80). The positive rates of intraoperative Cotton test and stress external rotation test were 34.8% (8/23) and 7.1% (1/14), respectively. The positive rates of passive pronation-external rotation and supination-external rotation stress tests during follow-up were 46.2% (12/26) and 34.6% (9/26). The incidences of postoperative short term (≤2 years) and medium-long term (>2 years) ankle pain were 37.7% (29/77) and 20.8% (16/77). MRI examination showed that the rates of injury to the anterior inferior tibiofibular ligament, deep medial malleolus deltoid ligament and posterior malleolus were 80.0% (24/30), 80.0% (24/30) and 76.7% (23/30). The incidence of ankle injury was 88.8% (71/80).Conclusions:It is highly probable that spiral fracture of the distal tibia is complicated with ipsilateral ankle injury. The medial malleolus, lateral malleolus, and posterior malleolus are prone to the following hidden injuries while the ankle joint is normally matched in the most cases: injury to the deep deltoid ligament in different degrees, rupture of the inferior tibiofibular anterior ligament and posterior malleolus fracture. Therefore, the ankle injury is likely to be missed in diagnosis. The secondary torsion injuries to the pronation-external rotation and supination-external rotation at the leg are likely to cause ipsilateral ankle injury.