Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Anterior segment optical coherence tomography angiography(AS-OCTA), as an emerging imaging technology for the anterior segment of the eye, has been increasingly applied in vascular imaging of the conjunctiva, sclera, cornea, and iris in recent years. This article focuses on the capability of AS-OCTA in providing morphological information of the anterior segment vasculature and quantitative measurements of vascular density, including key parameters such as vessel density, vessel diameter, and branching patterns. Compared to traditional imaging techniques(fuorescein angiography and indocyanine green angiography), AS-OCTA demonstrates significant potential in ophthalmic diagnosis and treatment due to its high resolution and richness of information, suggesting that it will become an indispensable tool in the future ophthalmic clinical practice. The purpose of this study is to explore the application value of AS-OCTA in the diagnosis and treatment of anterior segment diseases, as well as its importance in enhancing the accuracy of clinical decision-making.

Objective:To investigate the relationship between lumbar disc herniation and vertebral bone mineral density(BMD)of quantitative analysis of computed tomography(CT).Methods:Eighty patients with lumbar disc herniation who admitted to Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to June 2024 were included in the case group,and 30 healthy volunteers who underwent physical examination in hospital were included in the healthy control group during the same period.The vertebral BMD of all subjects was quantitatively analyzed by CT.The data,lumbar BMD value,lumbar bone mass loss and osteoporosis distribution of the two groups were compared at baseline.Results:There were no significant differences in gender,age,body mass index(BMI)and abdominal circumference of baseline data between the case group and the healthy control group(P>0.05).The BMD value of the fourth lumbar vertebra(L4)in the case group was lower than that in the healthy control group,and the difference was statistically significant(t=1.991,P<0.05).There were no significant differences in BMD value and mean BMD(Lmean BMD)of the fifth lumbar vertebra(L5)between the case group and the healthy control group(P>0.05).There was no statistically significant difference in the lumbar BMD value of healthy control group between different genders(P>0.05),and there was significant difference in Lmean BMD between different genders in the case group(t=2.063,P<0.05),while there were no statistically significant difference in the L4 BMD and L5 BMD of the case group between different genders(P>0.05).The difference of Lmean BMD values of the persons with same gender(male,female)between the case group and the healthy control group were statistically significant(t=2.570,3.300,P<0.05).The ratio of normal lumbar bone mass in the case group was 48.75%,which was lower than that in the healthy control group(70.00%),and the difference was statistically significant(x2=3.974,P<0.05).The ratio of osteoporosis in the case group was 18.75%,which was higher than that in the healthy control group(3.33%),and the difference of that between two groups was significant(x2=4.172,P<0.05).There was no significant difference in the ratio of bone mass loss between the two groups(P>0.05).Conclusion:CT quantitative analysis shows that the vertebral BMD value of the patients with lumbar disc herniation is significantly lower than that of persons of the healthy control group,which indicates that the decrease of BMD value might be related to the occurrence of lumbar disc herniation.

Objective:To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy.Methods:A total of 91 children with epilepsy admitted to the Women′s and Children′s Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women′s and Children′s Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048).Results:Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. Conclusion:Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.

Objective:To investigate the clinical characteristics, bleeding site distribution, and factors associated with hospitalization for surgical management in patients with refractory posterior epistaxis.Methods:This cross-sectional study retrospectively analyzed data from 3 473 patients with refractory posterior epistaxis treated at ENT department or Emergency Department of Affiliated Zhangzhou Hospital of Fujian Medical University, between January 2018 and December 2024. The demographic and clinical data of patients were collected. Univariate analyses and multivariable logistic regression were applied to identify factors associated with hospitalization for surgical intervention.Results:Among 3 473 patients (65.94%(2 290 cases) male; mean age (54±21) years), 46.96% (1 631 cases)were aged 41-69 years. Bleeding predominantly occurred at night (89.66%, 3 114 cases) and in winter (29.92%, 1 039 cases). The most frequent bleeding sites were the olfactory cleft (25.22%,876 cases) and inferior meatus vault (25.63%,890 cases), followed by the posterior regions of middle meatus (11.26%,391 cases), the foremost regions of nasal cavity (11.20%,389 cases), the nasal septum surface (11.23%,390 cases), the bottom of nasal cavity (9.42%,327 cases), and the others or uncertain sites (6.05%,210 cases). Endoscopic electrocautery was performed in 75.01% of cases. Overall, 2 715 patients required hospitalization for surgery. Univariate analysis identified older age (≥70 years), male sex, alcohol use, nighttime onset, winter season, hypertension, diabetes, and anticoagulant use as significantly associated with hospitalization ( χ2=6.51, 8.03, 5.11, -0.17, 7.53, 12.52, 6.83, 5.18, all P<0.05). Multivariable logistic regression confirmed older age ( OR=2.45, 95% CI: 1.81-7.50), winter season ( OR=9.55, 95% CI: 2.26-9.38), nighttime onset ( OR=6.78, 95% CI: 1.84-6.96), alcohol use ( OR=27.71, 95% CI: 11.97-64.14), hypertension ( OR=7.93, 95% CI: 1.64-11.84), and anticoagulant use ( OR=6.39, 95% CI: 1.06-9.47) as independent positive factors associated with hospitalization for surgical management (all P<0.05). Conclusions:Refractory posterior epistaxis most commonly affects individuals aged 41-69 years, with bleeding frequently originating from the olfactory cleft or inferior meatus vault, and exhibits seasonal (winter) and diurnal (nighttime) patterns. Independent factors significantly associated with the need for hospitalization and surgical intervention include older age, winter onset, nighttime onset, alcohol use, hypertension, and anticoagulant use. Identifying these factors may aid in risk stratification and clinical decision-making.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

OBJECTIVE: To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy. METHODS: A total of 91 children with epilepsy admitted to the Women's and Children's Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women's and Children's Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048). RESULTS: Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. CONCLUSION Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.
Humans ; Female ; Male ; Epilepsy/genetics* ; Child, Preschool ; Child ; Phenotype ; Genotype ; DNA Copy Number Variations/genetics* ; Infant ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Adolescent ; Exome Sequencing

Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. Methods Patients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). Conclusion After treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.

AIM:To investigate the therapeutic effect of recombinant human interleukin-37(rhIL-37)inter-vention on extracellular matrix deposition in human bronchial epithelial cells exposed to fine particulate matter(PM2.5),and to explore the underlying mechanisms.METHODS:An airway injury cell model was established using normal human bronchial epithelial 16HBE cells treated with various concentrations(6.25,12.5,25 and 50 mg/L)of PM2.5.Western blot and immunofluorescence were employed to assess the expression level of Wnt family member 5a(Wnt5a).The con-centration of PM2.5 that maximized Wnt5a expression was identified as the optimal concentration for further analysis.The cells were divided into 3 groups,PM2.5+siRNA,PM2.5+Wnt5a siRNA and control+Wnt5a siRNA,to evaluate the expres-sion of fibronectin,the secretion of IL-6 and IL-1β,and the production of reactive oxygen species(ROS).A subsequent set of experiments was organized into PM2.5+rhIL-37,PM2.5 and control groups to determine whether rhIL-37 down-regu-lates the expression of Wnt5a and fibronectin,and reduces the secretion of IL-6 and IL-1β.RESULTS:(1)After 24 h of exposure to various concentrations of PM2.5,the expression of Wnt5a in 16HBE cells was significantly elevated,except at 50 mg/L,compared with control group(P＜0.05).The highest Wnt5a expression was observed at 12.5 mg/L PM2.5(P＜0.01).(2)Fibronectin expression peaked after 24 h of exposure to PM2.5 at 12.5 mg/L(P＜0.01).(3)Successful knock-down of Wnt5a resulted in decreased levels of fibronectin and nuclear factor E2-related factor(Nrf2).Additionally,the production of ROS and the secretion of IL-6 and IL-1β were significantly reduced compared with control group(P＜0.01).(4)The administration of rhIL-37 before PM2.5 exposure led to decreased levels of Wnt5a,fibronectin and Nrf2 compared with PM2.5 group(P＜0.05).Furthermore,rhIL-37 treatment reduced the ROS production and the secretion of IL-6 and IL-1β(P＜0.05).CONCLUSION:In vitro cell models demonstrate that PM2.5 can induce extracellular matrix deposition in bronchial epithelial cells,potentially through the modulation of inflammatory response and oxidative stress influenced by Wnt5a.Additionally,rhIL-37 appears to mitigate inflammatory response and oxidative stress by down-regulating Wnt5a.