Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Objective To investigate the relationship between inflammation index and the severity of cere-bral small vessel disease.Methods A total of 168 patients with cerebral small vessel disease who were admit-ted to the Eighth People's Hospital of Hebei from August 2019 to October 2022 were selected as the study ob-jects.The study subjects were divided into cerebral small vessel disease with light burden(light burden group)and cerebral small vessel disease with medium-heavy burden(medium-heavy burden group)according to the total imaging burden score of cerebral small vessel disease.The basic data and systemic immune-inflam-matory index(SII),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and monocyte to lymphocyte ratio(MLR)were compared between the two groups.Spearman correlation analysis was used to evaluate the correlation between SII,NLR,PLR and MLR and the total imaging burden score of cerebral small vessel disease,and the influence of SII,NLR,PLR and MLR on the medium-heavy burden of cerebral small vessel disease was further analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of SII,NLR,PLR and MLR in the severity of cere-bral small vessel disease.Results The age,smoking history,hypertension history,neutrophil,platelet,SII,NLR,PLR and MLR in medium-heavy burden group were significantly higher than those in light burden group,and lymphocyte was significantly lower than that in light burden group,with statistical significance(P<0.05).Spearman correlation analysis showed that SII(r=0.377),NLR(r=0.516),PLR(r=0.486)and MLR(r=0.391)were positively correlated with the total imaging burden score of cerebral small vessel disease(P<0.001).Multivariate Logistic regression analysis showed that age,neutrophil,platelet,SII,NLR,PLR and MLR were independent risk factors for medium-heavy burden in cerebral small vessel disease,and lymphocyte was independent protective factor for medium-heavy burden in cerebral small vessel disease(P<0.05).ROC curve analysis results showed that the area under the curve of SII,NLR,PLR and MLR separately detected were 0.720(95%CI:0.646-0.787),0.802(95%CI:0.733-0.859),0.784(95%CI:0.714-0.843)and 0.728(95%CI:0.654-0.794),respectively.The area under the curve of the combined detection of the four indexes was higher than that of the single detection of each index(P<0.05).Conclusion The combined detection of SII,NLR,PLR and MLR has high predictive value for the severity of cerebral small vessel dis-ease,and is worthy of clinical promotion.

In recent years, with the clinical application of minimally invasive surgical techniques and comprehensive preoperative treatment, the survival rate of locally advanced esophageal cancer has significantly improved. However, the treatment of metastatic esophagogastric cancer still relies mainly on systemic therapy, and immunotherapy combined with chemotherapy has become a first-line treatment option, prolonging the survival of patients with metastatic esophageal cancer. Oligometastatic esophageal cancer is expected to bring survival benefits through systemic therapy combined with local treatment. The 2024 European clinical practice guidelines for oligometastatic esophagogastric cancer have been officially released, which standardize the definition, diagnosis, and treatment of oligometastatic esophageal cancer for further prospective studies. The authors interpret this guideline, especially by reviewing the clinical evidence of oligometastatic esophageal squamous cell carcinoma, to provide reference for the diagnosis and treatment of oligometastatic esophageal cancer in China.

The investigator-initiated trials （IIT）， as a widely existing form of clinical research both domestically and internationally， have attracted the attention of governments around the world due to the potential legal risks and issues they may cause， and the trend of legal supervision has gradually strengthened. The legal regulation of IIT in China is still in its early stages， with numerous legal issues that need to be clarified and sorted out. Based on the domestic and international legal reviews of IIT， this paper systematically sorted out the current situation of legal supervision of IIT in China and examined the existing issues， including weak legislative rules， incomplete regulatory systems， imperfect protection rules for research participants and informed consent systems， inadequate regulation of conflicts of interest management， and lax legal supervision of ethical review. Furthermore， this paper proposed suggestions for legal regulation of IIT from three perspectives， including strengthening legislation and emphasizing regulation， improving the mechanism for protecting research participants’ rights and interests， and balancing the legalization of IIT and the scientific development of clinical research， with a view to providing references for legal regulatory paths of IIT in China.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Mediastinal lymph node metastasis in esophageal squamous cell carcinoma is associated with a high metastasis rate and surgical difficulty. Minimally invasive surgical techniques,such as laparoscopy,allow for precise lymph node dissection in esophageal cancer with guidance for microanatomy. Different surgical concepts,including mesonephrectomy and the "concentric circle" anatomical model,have been proposed by scholars. The use of Da Vinci robots in esophageal surgery is advantageous over traditional laparoscopy in facilitating up-per mediastinal lymph node dissection and protecting recurrent laryngeal nerve (RLN) function. Based on the experience of our center,we explore robot-assisted lymph node dissection and quality control for esophageal cancer adjacent to the RLN,which can further standardize lymph node dissection in the upper mediastinum and improve perioperative quality of life and long-term survival.

Objective:To study the role of ML-SA5, an agonist of the lysosomal Ca 2+ channel transient receptor potential mucolipin 1 (TRPML1), in promoting lysosomal exocytosis to facilitate intracellular uranium removal and alleviate uranium-induced cellular damage for human renal proximal tubule epithelial cells (HK-2) exposed to uranyl acetate. Methods:HK-2 cells were divided into the following groups to be exposed to uranyl acetate at either 0 or 300 μmol/L for 24 h, followed by treatment with ML-SA5 and/or the lysosomal exocytosis inhibitor vacuolin-1 for 0.5 h: control group (Ctrl group), ML-SA5 group (M group), vacuolin-1 group (V group), ML-SA5 plus vacuolin-1 group (M+ V group), uranium exposure group (U group), uranium exposure plus ML-SA5 group (U+ M group), uranium exposure plus vacuolin-1 group (U+ V group), and uranium exposure plus ML-SA5 plus vacuolin-1 group (U+ M+ V group). We localized lysosome-associated membrane protein-1 (LAMP-1) on the plasma membrane (surface LAMP-1) by immunofluorescence assay; measured intracellular uranium content by inductively coupled plasma mass spectrometry; measured the level of kidney injury molecule-1 (KIM-1) by immunofluorescence assay; measured the rate of cell death with Calcein-AM/PI double staining; determined the subcellular localization of transcription factor EB (TFEB) and the levels of LAMP-1 and TRPML1 proteins by immunofluorescence assay; and measured the number of lysosomes using LysoTracker probes.Results:Compared with the Ctrl group, the U group showed significant increases in the surface LAMP-1 protein level ( t = 12.86, P < 0.05), KIM-1 protein level ( t = 18.86, P < 0.05), cell death rate ( t = 38.53, P < 0.05), TFEB nuclear translocation ( t = 9.12, P < 0.05), the protein expression levels of TFEB’s downstream target genes LAMP-1 ( t = 16.47, P < 0.05) and TRPML1 ( t = 32.33, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 7.75, P < 0.05). Compared with the U group, the U+ M group showed a significantly increased surface LAMP-1 level ( t = 3.33, P < 0.05) and significant decreases in the intracellular uranium level ( t = 5.01, P < 0.05), KIM-1 protein expression level ( t = 3.81, P < 0.05), and cell death rate ( t = 3.24, P < 0.05); all these effects in the U+ M group could be neutralized by the lysosomal exocytosis inhibitor vacuolin-1; and in addition, ML-SA5 significantly increased TFEB nuclear translocation ( t = 9.20, P < 0.05), the protein expression levels of LAMP-1 ( t = 3.05, P < 0.05) and TRPML1 ( t = 3.17, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 3.13, P < 0.05). Conclusions:The TRPML1 agonist ML-SA5 can promote lysosomal exocytosis to enhance intracellular uranium clearance and reduce uranium-induced cellular damage/death in uranium-loaded HK-2 cells, through activating TFEB to up-regulate lysosome biogenesis and TRPML1 protein expression.

The aim of this study was to prepare a self-assembled nanoparticle monkeypox vaccine candidate and study its immune response characteristics,so as to provide reference test data for its vaccine design.The antigen protein A29L-SpyTag and the backbone protein Mi3-SpyCatcher were expressed and purified by prokaryotic system,and nanoparticles A29L-Mi3 were prepared by chemical assembly,then the antibody titers were determined by ELISA,the antibody neutralization was determined by plaque test,and the cytokine secretion of lymphocytes was determined by flow cytometry to describe the immune response characteristics.Data showed that A29L-Mi3 nanoparticles were successfully prepared,and the particles were uniformly distributed in hollow cages,with an average particle size of(29±0.19)nm.After the A29L-Mi3 nanoparticle vaccine candidate was combined with SP01 adjuvant,the neutralizing antibody titer was stronger than that of the A29L protein candidate,and the A29L-Mi3 nanoparticle vaccine candidate could obtain neutralizing antibodies with similar titers after two immunizations.The level of mouse T lymphocyte immune response activated by the A29L-Mi3 nanoparticle vaccine candidate was higher than that of the A29L protein vaccine candidate.In conclusion,A29L-Mi3 protein nanoparticles with uniform structure have successfully assembled in vitro,which has strong immunogenicity and improved neutralization ability after combination with SP01 adjuvant,thus provided reference data for the optimization of immune programs.In addition,the level of cellular immune response is higher than that of A29L protein alone,which provides a reference for the design and development of monkeypox vaccine.