Objective:To investigate the expression of microRNA-4262 (miR-4262) and neuregulin 1 (NRG1) in non-small cell lung cancer (NSCLC) tissues and the relationship with prognosis.Methods:A total of 102 NSCLC patients who underwent surgical resection from January 2017 to February 2021 in Tongren People's Hospital of Guizhou Province were selected. The expression levels of miR-4262 and NRG1 were detected using real-time fluorescence quantitative PCR. The expression levels of miR-4262 and NRG1 in NSCLC cancer tissues and adjacent tissues, as well as NSCLC cancer tissues with different clinicopathological characteristics were analyzed. TargetScan database was used to predict the binding sites of miR-4262 and NRG1, and Pearson correlation coefficient was used to analyze the correlation between miR-4262 and NRG1 expression in NSCLC cancer tissues. Based on the mean expression levels of miR-4262 and NRG1 in NSCLC cancer tissues, the patients were divided into high miR-4262 expression group (miR-4262≥1.52, n=54) and low miR-4262 expression group (miR-4262<1.52, n=48), high NRG1 expression group (NRG1≥0.79, n=54) and low NRG1 expression group (NRG1<0.79, n=48). Kaplan-Meier survival curves were plotted to compare the 3-year overall survival (OS) rates between groups. Cox proportional risk regression model was used to analyze the influencing factors for the prognosis of NSCLC patients. Results:The expression level of miR-4262 was significantly higher in NSCLC tumor tissues compared to adjacent tissues (1.52±0.21 vs. 1.11±0.20), while NRG1 expression level was lower (0.79±0.11 vs. 1.06±0.11), there were statistically significant differences ( t=14.22, P<0.001; t=-15.13, P<0.001). The expression of miR-4262 was negatively correlated with NRG1 in cancer tissues of NSCLC patients ( r=-0.74, P<0.001). There were statistically significant differences in the expression levels of miR-4262 and NRG1 of NSCLC patients in tumor differentiation ( t=2.80, P=0.006; t=-2.80, P=0.006), TNM stage ( F=24.36, P<0.001; F=17.66, P<0.001), and lymph node metastasis ( t=4.02, P<0.001; t=-3.98, P<0.001). At the end of the follow-up period, 57 patients survived, and 45 died, with a 3-year OS rate of 55.88%. Patients with high miR-4262 expression had a significantly lower 3-year OS rate compared to those with low miR-4262 expression (35.19% vs. 79.17%), patients with high NRG1 expression had a significantly higher 3-year OS rate than those with low NRG1 expression (77.78% vs. 31.25%), there were statistically significant differences ( χ2=22.58, P<0.001; χ2=27.26, P<0.001). Univariate analysis showed that, age ( HR=2.47, 95% CI: 1.05-5.80, P=0.038), maximum tumor diameter ( HR=3.75, 95% CI: 1.61-8.74, P=0.002), differentiation degree ( HR=3.03, 95% CI: 1.32-6.96, P=0.009), TNM stage (stage Ⅱ, HR=3.45, 95% CI: 1.10-10.83, P=0.034; stage Ⅲ, HR=6.72, 95% CI: 2.03-22.26, P=0.002), lymph node metastasis ( HR=3.00, 95% CI: 1.29-6.96, P=0.010), miR-4262 expression ( HR=3.72, 95% CI: 1.48-9.35, P=0.005), and NRG1 expression ( HR=0.30, 95% CI: 0.13-0.73, P=0.008) were all influencing factors for OS in NSCLC patients. Multivariate analysis showed that, differentiation degree ( HR=5.47, 95% CI: 1.63-18.34, P=0.006), TNM stage (stage Ⅲ, HR=5.56, 95% CI: 1.23-25.14, P=0.026), lymph node metastasis ( HR=3.72, 95% CI: 1.19-11.60, P=0.024), miR-4262 expression ( HR=8.56, 95% CI: 2.26-32.41, P=0.002), and NRG1 expression ( HR=0.26, 95% CI: 0.09-0.76, P=0.014) were all independent influencing factors for OS in NSCLC patients. Conclusions:The expression of miR-4262 is high and the expression of NRG1 is low in cancer tissues of NSCLC patients. The 3-year OS rate of patients with high miR-4262 expression is lower than that of patients with low miR-4262 expression, and the 3-year OS rate of patients with high NRG1 expression is higher than that of patients with low NRG1 expression. Differentiation degree, TNM stage, lymph node metastasis, miR-4262 and NRG1 are all independent influencing factors for the prognosis of NSCLC patients.

Objective:To analyze the research programs of clinical trials related to the TCM treatment of Hashimoto's thyroiditis (HT) at home and abroad; To provide references for the follow-up study of TCM treatment of HT.Methods:All clinical research registration plans for TCM prevention and treatment of HT were retrieved from the Chinese Clinical Trial Registry, the International Traditional Medicine Clinical Trial Registry, and the WHO International Clinical Trial Registration Platform from the establishment of the databases to December 31, 2024. Excel 2019 and GraphPad Prism 9.0 were used for data processing, and the basic characteristics, study types, randomized methods, interventions, outcome indicators and other registration information of registered trials with the frequency analysis.Results:A total of 31 clinical trials were included in this study, and the number of registered studies has gradually increased since 2018, which involving 23 clinical institutions in 9 provincial-level administrative regions until 2024. The region with the highest number of registrations is Shanghai (14 items). The funding sources were mainly local financial support and hospital funding. The research types were mostly intervention studies (30 items). The main research design type was randomized parallel controlled trials (27 items).Conclusions:At present, the overall number of registration studies on TCM prevention and treatment of HT is relatively small. However, in recent years, researchers have paid more attention to the registration of clinical trials in this field. The regional distribution of existing trial registration is not balanced, and the research design scheme needs to be improved.

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

Objective To screen the anti-CD22-specific nanobodies to provide a basis for immunotherapy agents. Methods The naive phage nanobody library was constructed and its diversity was analyzed. Three rounds of biotinylated streptavidin liquid phase screening were performed by using biotinylated CD22 antigen as the target, and the sequence of nanobodies against CD22 were identified by ELISA and gene sequencing. Results The capacity of the constructed naive phage nanobody library was 3.89×10⁹ CFU/mL, and the insertion of effective fragments was higher than 85%. Based on this library, seven anti-human CD22 nanobodies were screened, and the amino acid sequence comparison results showed that the overall similarity was 70.34%, and all of them were hydrophilic proteins. The results of protein-protein complex docking prediction showed that the mimetic proteins of the five nanobody sequences could be paired and linked to CD22, and the main forces were hydrophobic interaction and hydrogen bonding. Conclusion This study provided a basis for the study of chimeric antigen receptor T cells targeting CD22, successfully constructed the natural phage nanobody library and obtaining five anti-CD22-specific nanobodies.
Camelus/immunology* ; Single-Domain Antibodies/chemistry* ; Peptide Library ; Humans ; Animals ; Sialic Acid Binding Ig-like Lectin 2/genetics* ; Amino Acid Sequence ; Molecular Docking Simulation

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

ObjectiveTo investigate the correlation of the serum levels of aminotransferases and their ratios with liver inflammation activity in pediatric chronic hepatitis B （pCHB） patients， and to provide a basis for selecting the dominant population for treatment. MethodsThis study was conducted among 1 267 pCHB patients who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to August 2022 and these patients did not receive antiviral therapy. The patients were analyzed in terms of demographic features， blood routine， blood biochemistry， HBV serological markers， and liver biopsy data. According to liver inflammation activity based on liver biopsy， the patients were divided into no or mild inflammation activity （G0‍ ‍—‍ ‍G1） group and significant inflammation activity （G2‍ ‍—‍ ‍G4） group. The serum levels of aminotransferases and their ratios were compared between groups， and their correlation with liver inflammation activity in pCHB patients was analyzed. Additionally， the patients were stratified by the age， and the relationship between serum aminotransferase levels and liver inflammation activity was analyzed in each age group. For comparison of continuous data between two groups， the independent samples t-test was used when the data were normally distributed， while the Mann-Whitney U test was used when the data were not normally distributed； the chi-square test was employed for comparison of categorical data between two groups. A Spearman’s correlation analysis was performed for correlation assessment. ResultsAmong the 1 267 pCHB patients， there were 468 （36.9%） in the G0‍ ‍—‍ ‍G1 group and 799 （63.1%） in the G2‍ ‍—‍ ‍G4 group， and there were significant differences between the two groups in the levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， AST/ALT ratio， gamma-glutamyl transpeptidase （GGT）， total bilirubin， direct bilirubin， HBeAg quantification， low-density lipoprotein， and platelet count （PLT） （all P<0.05）. The correlation analysis showed that liver inflammation activity was negatively correlated with PLT and low-density lipoprotein （both P<0.05） and was positively correlated with GGT， total bilirubin， direct bilirubin， and HBeAg titer （all P<0.05）， while it was not significantly correlated with ALT， AST， and AST/ALT ratio （all P>0.05）. In the 0‍ ‍—‍ ‍12 years group， the 13‍ ‍—‍ ‍18 years male group， and the 13‍ ‍—‍ ‍18 years female group， liver inflammation activity aggravated with the increases in the serum levels of ALT and AST， and there were significant differences between groups （all P<0.05）. In the 0‍ ‍—‍ ‍12 years group， there was a significant difference in significant liver inflammation activity between the AST/ALT ratio >1 group and the AST/ALT ratio ≤1 group （P<0.001）. Among the 1 267 patients， 447 （35.28%） had an ALT level of <2×upper limit of normal （ULN）， among whom 196 （43.85%） had G≥2 liver inflammation， accounting for 15.47% of all children enrolled. ConclusionLiver inflammation activity is not significantly correlated with ALT， AST， and AST/ALT ratio in pCHB patients， suggesting that the serum levels of aminotransferases cannot truly reflect liver inflammation activity in pCHB patients with an aminotransferase level of <2×ULN. In clinical practice， liver biopsy should be performed for children with an aminotransferase level of <2×ULN to clarify whether antiviral therapy should be performed.

ObjectiveTo investigate the association between maternal infection with the SARS-CoV-2 Omicron variant during pregnancy and common infant illnesses and neurodevelopment. MethodsA cohort study was designed, selecting 113 pregnant women from Shanghai’s Pudong New Area who tested positive for SARS-CoV-2 by nasal swab reverse transcription-polymerase chain reaction (RT-PCR) and were transported to medical institutions for isolation treatment between March and May 2022. These women constituted the pregnancy infection group. Concurrently, 226 pregnant women from the same region and time period who did not infect with SARS-CoV-2 were selected as the control group. Both groups were followed up until delivery and their offspring’s one year old. The differences in the risk of common infant illnesses and the level of infant’s neurodevelopment at age one were compared between the two groups. ResultsNo significant difference was found in the incidence of common illnesses before one year of age between the pregnancy infection group and the control group. Additionally, no significant differences were found in any domain scores of the ASQ-3 between the two groups. ConclusionMaternal infection with SARS-CoV-2 Omicron variant during pregnancy was not statistically significant correlated with common infant illnesses in infancy and neurodevelopment at age one.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Objective To construct a predictive model for cerebral small vessel disease (CSVD) MRI burden based on β2-microglobulin (β2-MG) and lipoprotein(a) [Lp(a)], analyze its predictive value, and validate the model. Methods A total of 138 CSVD patients admitted to Anhui No.2 Provincial People’s Hospital from February 2023 to August 2024 were enrolled. Patients were divided into a low-burden group (n=63) and a moderate/severe burden group (n=75) according to the CSVD MRI burden scoring criteria. The related clinical data were compared between the two groups. Binary logistic regression analysis was used to identify independent factors for CSVD moderate/severe MRI burden. A nomogram predictive model was constructed based on these factors and its performance was evaluated. Results The proportions of male patients, as well as those with a history of diabetes or hypertension, were significantly higher in the moderate/severe burden group than those in the low burden group. Additionally, the age of patients in the moderate/severe burden group was significantly older, and the levels of β2-MG, Lp(a), and homocysteine (Hcy) were higher than those in the low burden group (P＜0.01). Binary logistic regression analysis revealed that hypertension, diabetes, β2-MG, and Lp(a) were independent factors for CSVD moderate/severe MRI burden (P＜0.05). The nomogram predictive model based on these four factors had a cut-off value of 0.467 0, with an area under curve (AUC) of 0.838 7 (95%CI 0.760 8-0.916 6) in the training set (n＝97) and 0.854 1 (95%CI 0.742 1-0.966 1) in the internal validation set (n＝41) . The calibration curve demonstrated good agreement between predicted and observed values. Decision curve analysis (DCA) indicated that the nomogram model had good clinical utility. Conclusions The nomogram model based on β2-MG and Lp(a) has high predictive performance in assessing the risk of CSVD moderate/severe MRI burden, with good discrimination and calibration.