OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

Objective:To observe the changes of peripheral blood T cell subsets and serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 contents in narcolepsy type 1 (NT1) patients and their correlations with narcolepsy, and provide basis for finding the biological markers of narcolepsy.Methods:A retrospective analysis was performed. From March 2022 to December 2023, 23 patients with NT1 admitted to Epilepsy and Sleep Disorder Center, Second Affiliated Hospital of Harbin Medical University and 23 healthy controls underwent physical examination of nervous system in our center were enrolled. T lymphocyte subsets CD4 + and CD8 + in peripheral blood were calculated by flow cytometry. Serum TNF-α and IL-6 contents were detected by enzyme-linked immunosorbent assay. Multivariate Logistic regression was used to determine the correlations of NT1 with CD4 + T lymphocyte count and IL-6 and TNF-α contents, and diagnostic values of CD4 + T lymphocyte and TNF-α in NT1 were evaluated via area under receiver operating characteristics (ROC) curve. Results:Compared with the healthy controls, the NT1 patients had significantly increased peripheral blood CD4 + T lymphocyte count ([820.61±316.87] /μL vs. [1121.04±387.47] /μL), and significantly higher serum TNF-α and IL-6 contents ([39.97±10.64] pg/mL vs. [57.01±19.92] pg/mL; [22.50±6.09] pg/mL vs. [33.66±17.28] pg/mL, P<0.05). No significant difference in peripheral blood CD8 + T lymphocyte count was noted between the 2 groups ([668.65±276.45] pg/mL vs. [592.52±217.78] pg/mL, P>0.05). Multivariate Logistic regression showed that CD4 + T lymphocyte count and serum TNF-α content were independent risk factors for NT1 ( OR=1.004, 95% CI: 1.001-1.006, P=0.007; OR=1.133, 95% CI: 1.032-1.243, P=0.009). Area under ROC curve of the two combined indexes was 0.881(95% CI: 0.784-0.977, P=0.001), enjoying sensitivity of 0.783 and specificity of 0.870. Conclusion:Combination of peripheral blood CD4 + T lymphocyte count and serum TNF-α content has high diagnostic performance in predicting NT1.

Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Objective:To explore the changes in serum indoleamine 2, 3-dioxygenase (IDO) and kynurenic acid (KYNA) levels in preterm infants diagnosed with bronchopulmonary dysplasia (BPD).Methods:A nested case-control study was conducted. The inclusion criteria covered premature infants with less than 32 weeks of gestational age within 24 h post-birth, from December 1, 2021, to December 31, 2022, at Children's Hospital of Soochow University. Those diagnosed with BPD were allocated to the BPD group ( n=35). Non-BPD preterm infants matching the BPD cases in terms of gestational age (within one week difference) and birth weight (within a 150 g difference) were selected in a 1∶1 ratio for the control group ( n=35). Serum levels of IDO and KYNA were measured on days 1, 7, 14, and 28 postnatally. Differences in serum IDO and KYNA levels were analyzed between the BPD and control groups and among infants with mild BPD versus moderate-to-severe BPD. The association between serum IDO and KYNA levels with the severity of BPD was also assessed. Statistical analysis was conducted using independent samples t-tests and Spearman's correlation analysis. Results:Elevated levels of serum IDO on days 7, 14, and 28 postnatally [(60.68±9.37) vs. (50.66±10.46), (57.81±11.07) vs. (44.45±8.20), and (50.62±10.77) vs. (41.31±7.74) pg/ml; t=4.21, 5.73, and 4.15, respectively] as well as increased serum KYNA levels on days 14 and 28 [(439.31±41.22) vs. (368.99±68.79), (376.97±45.74) vs. (325.50±60.07) μmol/L; t=5.18 and 4.03, respectively] were observed in the BPD group compared to the control group, with all differences being statistically significant (all P<0.05). Furthermore, positive correlations were observed between serum IDO levels and BPD severity on the 7th, 14th, and 28th days ( r=0.546, 0.495, and 0.502, all P<0.05), as well as between serum KYNA levels and BPD severity on the 14th and 28th days ( r=0.536 and 0.458, both P<0.05). Conclusion:Elevated serum levels of IDO and KYNA in infants with BPD suggest these metabolites may play a role in the pathogenesis and progression of BPD.

Objective To analyze the clinical application of Extracorporeal Cardiopulmonary Resuscita-tion(ECPR)in patients with refractory cardiac arrest in the emergency department and to investigate the factors affecting survival and neurological outcomes.Methods A retrospective analysis was conducted on the clinical data of 61 patients who underwent Extracorporeal Membrane Oxygenation(ECMO)for cardiopulmonary resuscitation at the emergency department from January 2021 to March 2024.The hospital discharge survival rate,favorable neuro-logical outcome rate,and incidence of complications were summarized.Factors affecting survival and neurological outcomes were also analyzed.Results In a study of 61 patients,the ECMO weaning success rate was 55.7%,the hospital discharge survival rate was 29.5%,the favorable neurological prognosis rate was 21.3%,and the incidence of complications was 47.5%.The proportion of initial cardiac rhythm being shockable was significantly higher in the survival group compared to the mortality group.The ECMO establishment time,low-flow time,and pre-ECMO blood lactate levels were all significantly lower in the survival group than in the mortality group.The pre-ECMO blood pH level was higher in the survival group.The ECMO maintenance time and ICU stay were significantly longer in the survival group than in the mortality group,with all P-values being less than 0.05,indicating statistically significant differences.Patients with an initial shockable cardiac rhythm and low-flow time≤60 minutes had a better favorable neurological prognosis rate.Conclusions Extracorporeal cardiopulmonary resuscitation can provide effective life support for patients with refractory cardiac arrest.Patients with an initial shockable rhythm,lower blood lactate levels and higher pH levels before ECMO support,and shorter low-flow time have a better prognosis.

Objective To analyze the clinical application of Extracorporeal Cardiopulmonary Resuscita-tion(ECPR)in patients with refractory cardiac arrest in the emergency department and to investigate the factors affecting survival and neurological outcomes.Methods A retrospective analysis was conducted on the clinical data of 61 patients who underwent Extracorporeal Membrane Oxygenation(ECMO)for cardiopulmonary resuscitation at the emergency department from January 2021 to March 2024.The hospital discharge survival rate,favorable neuro-logical outcome rate,and incidence of complications were summarized.Factors affecting survival and neurological outcomes were also analyzed.Results In a study of 61 patients,the ECMO weaning success rate was 55.7%,the hospital discharge survival rate was 29.5%,the favorable neurological prognosis rate was 21.3%,and the incidence of complications was 47.5%.The proportion of initial cardiac rhythm being shockable was significantly higher in the survival group compared to the mortality group.The ECMO establishment time,low-flow time,and pre-ECMO blood lactate levels were all significantly lower in the survival group than in the mortality group.The pre-ECMO blood pH level was higher in the survival group.The ECMO maintenance time and ICU stay were significantly longer in the survival group than in the mortality group,with all P-values being less than 0.05,indicating statistically significant differences.Patients with an initial shockable cardiac rhythm and low-flow time≤60 minutes had a better favorable neurological prognosis rate.Conclusions Extracorporeal cardiopulmonary resuscitation can provide effective life support for patients with refractory cardiac arrest.Patients with an initial shockable rhythm,lower blood lactate levels and higher pH levels before ECMO support,and shorter low-flow time have a better prognosis.

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.
Flavonoids/metabolism* ; Fruit/genetics* ; Gene Expression Profiling/methods* ; Gene Expression Regulation, Plant ; Lycium/metabolism* ; Metabolic Networks and Pathways ; Transcriptome

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development