Objective To explore the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced resectable non-small cell lung cancer (NSCLC). Methods The clinical data of patients with stage ⅡA-ⅢB NSCLC who underwent surgical treatment after receiving neoadjuvant immunotherapy combined with chemotherapy or chemotherapy alone at the First People’s Hospital of Jining between April 2021 and January 2024 were retrospectively analyzed. According to the preoperative neoadjuvant regimens, the patients were divided into a combined group and a chemotherapy group, and the clinical data of the two groups were compared. Results A total of 66 patients were included, including 61 males and 5 females. There were 53 patients in the combined group with a mean age of (63.40±6.80) years, and 13 patients in the chemotherapy group with a mean age of (58.62±8.30) years. There was a statistical difference in age between the two groups (P＜0.001), while no statistical difference was observed in other baseline data (P>0.05). The major pathological response rates in the combined group and the chemotherapy group were 54.7% and 23.1%, respectively (P=0.041), and the pathological complete response rates were 39.6% and 0.0%, respectively (P=0.006). The operative time in the combined group was shorter (P=0.039). There were no statistical differences between the two groups in intraoperative blood loss, duration of postoperative tube carrying, incidence of postoperative complications, overall survival, or event-free survival (P>0.05). Conclusion Surgical treatment following neoadjuvant immunotherapy combined with chemotherapy is safe and feasible, and its long-term efficacy requires further follow-up for confirmation.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

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.

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 diagnosis，therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed，and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome，10 males and 11 females，aged 5 days to 10 years old. Compared with the adult-type group，the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05)，a high concomitant rate of intracardiac malformations (100% vs. 40%， P=0.002)，a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg， P=0.016]，a high incidence of pulmonary hypertension(91.0% vs. 50.0%， P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0， P=0.034)，prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h， P=0.007]，and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d， P<0.001]. Eleven cases underwent surgical treatment only，and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%，and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.

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

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.

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.