Objective To explore the predictive value of peripheral blood cells in the efficacy of neoadjuvant immunotherapy combined with chemotherapy for esophageal squamous cell carcinoma. Methods A retrospective study was conducted on patients with esophageal squamous cell carcinoma (clinical stages Ⅱ-Ⅳa) who underwent neoadjuvant immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from April 2020 to November 2023. According to whether the pathology was completely relieved after treatment, patients were divided into a pathological complete remission group and a pathological incomplete remission group. The College of American Pathologists criteria were used to evaluate the tumor pathological regression grade (TRG) after neoadjuvant therapy (TRG=0, 1 defined as a good efficacy group, TRG=2, 3 defined as a poor efficacy group). Results A total of 92 patients with esophageal squamous cell carcinoma were collected, including 72 males and 20 females. The average age was (65.86±7.66) years. The complete remission of pathology was closely related to the number of lymphocytes in the blood before treatment (P=0.019). The area under the curve (AUC) for predicting complete remission of esophageal squamous cell carcinoma after neoadjuvant immunotherapy combined with chemotherapy was 0.678, the maximum Youden index was 0.328, and the optimal cutoff value was 1.845. The incidence of postoperative pulmonary infection in the pathological incomplete remission group was higher than that in the pathological complete remission group (25.0% vs. 5.6%, P=0.030). Using the optimal cutoff value, there were statistically significant differences in pathological N stage and pathological TNM stage between patients with lymphocyte counts <1.845×109/L and ≥1.845×109/L (P<0.05). Treatment response (by TRG) was significantly associated with the pretreatment red blood cell count (P=0.009). The AUC for predicting a good TRG response was 0.669, with a maximum Youden index of 0.385 and an optimal cutoff value of 4.235. Between the good and poor response groups, there were statistically significant differences in postoperative pathological T stage (P<0.001), N stage (P=0.041), and TNM stage (P＜0.001). When stratified by the optimal cutoff value, there were statistically significant differences in age (P＜0.001) and the prevalence of hypertension (P=0.022) between patients with red blood cell counts <4.235×1012/L and ≥4.235×1012/L. Conclusion A pretreatment absolute lymphocyte count ≥1.845×109/L and a red blood cell count <4.235×1012/L are good predictors for pathological complete response and a good pathological response, respectively, following neoadjuvant immunotherapy combined with chemotherapy in patients with esophageal squamous cell carcinoma.

Resectable non-small cell lung cancer (NSCLC) is prone to recurrence and metastasis after simple surgery. Although patients can benefit from preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy, the 5-year survival rate is not significantly improved. In recent years, with the rise of immunotherapy, NSCLC immunotherapy has gradually received attention. Many explorations have been made on resectable NSCLC immunotherapy, and satisfactory results have been obtained. With the release of multiple phase 3 research results, a new chapter in resectable NSCLC immunotherapy has officially opened. However, there are still many problems in the immunotherapy of resectable NSCLC. This article reviews the current relevant research and provides reference for clinical application.

Objective:To analyze and compare the short-term efficacy and safety of sintilimab and tislelizumab in neoadjuvant therapy for advanced esophageal squamous cell carcinoma.Methods:The clinical data of 95 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (paclitaxel + nedaplatin) combined with immunotherapy in the Department of Thoracic Surgery of the Affiliated Hospital of North Sichuan Medical College from January 2021 to October 2022 were collected. According to the different use of immune drugs, they were divided into the sintilimab group ( n=58) and the tislelizumab group ( n=37). The objective remission rate (ORR), adverse reactions, R0 resection rate, pathological complete response (pCR) rate, etc. were analyzed and compared between the two groups after neoadjuvant therapy. Results:After 2 cycles of neoadjuvant therapy, the sintilimab group and the tislelizumab group had a similar ORR [72.4% (42/58) vs. 56.8% (21/37), χ2=2.48, P=0.115]. The main adverse reactions of the two groups of patients included gastrointestinal reactions (nausea, vomiting, diarrhea), hematological toxicity, hypothyroidism, alopecia, liver and kidney dysfunction, pneumonia, etc. The incidence of grade 3 adverse reactions was less than 15%, with no grade 4 adverse reactions. The incidence of hypothyroidism in the sintilimab group was significantly higher than that in the tislelizumab group [56.9% (33/58) vs. 16.2% (6/37) ], with a statistically significant difference ( χ2=15.45, P<0.001) ; There was no statistically significant difference in surgical resection ( χ2=1.26, P=0.661) and pCR rate [31.0% (18/58) vs. 32.4% (12/37), χ2=0.02, P=0.886] between the two groups of patients. In terms of postoperative complications, both groups of patients experienced partial pulmonary infections and anastomotic fistulas, but the incidence was relatively low [19.0% (11/58) vs. 24.3% (9/37), 3.4% (2/58) vs. 2.7% (1/37) ], with no statistically significant difference ( χ2=0.39, P=0.532; χ2<0.01, P>0.999) . Conclusion:For preoperative neoadjuvant therapy of advanced esophageal squamous cell carcinoma, the use of either sintilimab or tislelizumab in addition to chemotherapy has good short-term efficacy and safety. Thyroid function should be monitored carefully when using sintilimab.

Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical sig-nificance of patients with β-thalassemia.Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022.The expression level of miR-124-3p was detected.Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR.The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was eval-uated.Results Compared with healthy control individuals,the expression of miR-124-3p was significantly up-reg-ulated in patients with β-thalassemia(P＜0.001).The genotype of miR-124-3p high expression group was 84.2%β0(16/19),the genotype of low expression group was 55.6%β+(10/18).ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia(AUC:0.842).Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p.Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia,and ERF is negatively reg-ulated by miR-124-3p.miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P＜0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P＜0.05 or P＜0.01),while there was no significant difference in the above parameters in the X-NC group(all P＞0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01),and there was no significant difference in all parameters in the X-NC group(all P＞0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.

Brain-computer interfaces (BCIs) have become one of the cutting-edge technologies in the world, and have been mainly applicated in medicine. In this article, we sorted out the development history and important scenarios of BCIs in medical application, analyzed the research progress, technology development, clinical transformation and product market through qualitative and quantitative analysis, and looked forward to the future trends. The results showed that the research hotspots included the processing and interpretation of electroencephalogram (EEG) signals, the development and application of machine learning algorithms, and the detection and treatment of neurological diseases. The technological key points included hardware development such as new electrodes, software development such as algorithms for EEG signal processing, and various medical applications such as rehabilitation and training in stroke patients. Currently, several invasive and non-invasive BCIs are in research. The R&D level of BCIs in China and the United State is leading the world, and have approved a number of non-invasive BCIs. In the future, BCIs will be applied to a wider range of medical fields. Related products will develop shift from a single mode to a combined mode. EEG signal acquisition devices will be miniaturized and wireless. The information flow and interaction between brain and machine will give birth to brain-machine fusion intelligence. Last but not least, the safety and ethical issues of BCIs will be taken seriously, and the relevant regulations and standards will be further improved.
Humans ; Brain-Computer Interfaces ; Medicine ; Algorithms ; Artificial Intelligence ; Brain

Objective:To investigate the relationship between carotid atherosclerosis(CAS)and subclinical left ventricular(LV)dysfunction in type 2 diabetes mellitus patients with preserved LV ejection fraction(LVEF).Methods:A total of 120 patients with type 2 diabetes mellitus who had LVEF≥50% were selected in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University from June 2021 to October 2021. The global longitudinal strain(GLS)was obtained by two-dimensional speckle tracking echocardiography(STE)to assess subclinical LV systolic function. The mitral ratio of peak early to late diastolic filling velocity(E/A), and mitral velocity to early diastolic velocity of the mitral annulus(E/E′)ratio were obtained by pulsed tissue Doppler echocardiography to assess LV diastolic function. Acrroding to bilateral carotid ultrasound examination, the subjects were divided into normal carotid arteries group( n=46) and CAS group( n=74). Demographics and biochemical parameters were compared between two groups. Binary logistic regression and Pearson correlation analysis were used to evaluate the relationship between CAS and subclinical LV dysfunction. Results:The CAS group had a higher proportion of men, older age, and a longer duration of diabetes than the normal carotid arteries group(all P<0.05). There was no difference in LVEF and GLS between the two groups [normal carotid arteries group vs CAS group, LVEF: (60.72±4.73)% vs(60.07±4.28)%; GLS: (18.24±3.72)% vs(17.81±3.47)%, respectively; both P>0.05]. However, compared with normal carotid arteries group, E/A ratio was decreased and E/E′ ratio was significantly increased in CAS group(both P<0.01). Pearson correlation analysis showed that GLS was not correlated with carotid plaque thickness and carotid intima-media thickness(CIMT; both P>0.05). By contrast, E/E′ ratio was positively correlated with carotid plaque thickness and CIMT(both P<0.05). Binary logistic regression analysis showed that GLS and E/E′ ratio were not associated with CAS( both P>0.05). However, decreased E/A ratio was significantly associated with the existence of CAS( OR=0.09, 95% CI 0.01-0.67, P=0.018). Conclusions:In type 2 diabetes mellitus patients without overt heart failure and with preserved LVEF, the occurrence of CAS is not associated with subclinical LV systolic impairment assessed by GLS, but is significantly associated with LV diastolic dysfunction, and is independent of traditional cardiovascular risk factors.

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.
8-Hydroxy-2'-Deoxyguanosine ; Animals ; Antibodies, Monoclonal ; Gold ; Gold Colloid/chemistry* ; Metal Nanoparticles ; Mice ; Sensitivity and Specificity

Objective:To investigate the safety and efficacy of echocardiography-guided trans-right-ventricular percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in a healthy sheep model, and to observe the pathological changes of myocardium in ablation area one year later.Methods:Twelve sheep were divided into PIMSRA group ( n=6) and sham group ( n=6). In PIMSRA group, a radiofrequency (RF) electrode was inserted to the interventricular septum (IVS) with maximum power of 80 Watts for 5 minutes. In the sham group, RF electrode tip was positioned in IVS segment but without the RF power delivery. Electrocardiogram (ECG), echocardiography, myocardial contrast echocardiography(MCE) were performed to assess the efficacy of PIMSRA at postoperative immediately, 2-week, 1-month, 2-month, 3-month, 6-month and 12-month during the follow-up. The following parameters were recorded, including the thickness of ablation area, the systolic wall thickening rate and amplitude of movement of the ablated region, left ventricular outflow tract pressure gradient (LVOT PG), and left ventricular ejection fraction (LVEF), mitral valve early diastolic peak velocity(E), late diastolic peak velocity(A) and the E/A ratio, peak velocity of early diastolic mitral annular motion(E′), peak velocity of late diastolic mitral annular motion(A′), and the E′/A′ ratio.For both groups, the myocardial biomarkers of troponin I, myoglobin and isoenzymes of creatine kinase were tested before the ablation and 3 h after the ablation, and again after 2 weeks. Tissue pathology examinations were performed at the end of study. Results:None of the animals in both groups was observed to have pericardial tamponade during perioperative period.Immediately after the procedure, septal hypokinesis was seen in all PIMSRA group animals, the systolic wall thickening rate and amplitude of movement of the ablated region were significantly decreased ( P<0.001), which was sustained until 12 months.In Sham group, there were no significant differences in the wall thickening rate and amplitude of movement of the operated region(all P>0.05).The thickness of the ablation area in the PIMSRA group was significantly increased immediately after the procedure( P<0.001), decreased to baseline level at 1-week ( P=0.931), and significantly increased at 3-month ( P<0.001).In the Sham group, the IVS thickness was significantly increased immediately after the procedure( P=0.005), decreased to baseline level at 1-week ( P=0.027), then has no further significant changes.There were no significant differences in LVEF, E/A, E′/A′ between PIMSRA and Sham group(all P>0.05).MCE showed the thickness of the ablation area was significantly decreased in the PIMSRA group 12 months after the operation.In both groups, troponin I increased significantly 3 h after the operation(all P<0.005), which decreased to baseline level 2 weeks later(all P>0.05). ECG showed that all the sheep had normal sinus rhythm. Pathological examinations revealed the tissue in the ablation area was fibrotic, having clear boundary with the surrounding normal tissue and no carbonization was observed 1 year later. Conclusions:Echocardiography-guided trans-right-ventricular PIMSRA produced precisely ablated myocardial tissues, reduced the IVS thickness significantly, preserved the global left ventricular function. All the sheep had normal sinus rhythm and without pericardial tamponade in 1 year follow-ups. Echocardiography-guided trans-right-ventricular PIMSRA is a safe and effective minimally invasive treatment for septal reduction therapy.