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Abstract Previous studies have demonstrated prolonged occlusion flow-mediated dilatation (PO-FMD) could reduce cannulation failure rates and decrease radial artery pulsation loss during trans-radial coronary angiography. However, the time and degree of radial artery dilatation induced after PO-FMD were unclear. This study aimed to evaluate the degree and duration of the radial artery dilation after PO-FMD, and the time point at which the radial artery diameter is expanded to the maximum. This was a prospective observational study. According to the Chinese guideline on the primary prevention of cardiovascular diseases, 142 patients awaking from general anesthesia were divided into two groups: low-risk (LR) group and high-risk (HR) group. Firstly, the baseline radial artery diameter was measured on the left wrist using ultrasound in both groups. Subsequently, the radial artery diameters were obtained continuously at the same location for 5 min after PO-FMD. The baseline radial artery diameter, the maximum radial artery diameter, and the duration of radial artery dilation in the two groups were recorded. The time point at which the radial artery diameter is expanded to the maximum in the LR group and HR group was 26.49 ± 11.69 s and 46.27 ± 12.03 s, respectively (P

Tailoring the morphologies and optical properties of the 2D and hierarchical nanostructures self-assembled by the π-conjugated molecules is both interesting and challenging. Herein, a series of 2D ribbon-like nanostructures with single or multiple H-aggregated perylene bisimides (PBI) monolayer and hierarchical nanostructures (including straw-like, dumbbell-shaped, and rod-like nanostructures) are fabricated by solution self-assembly of three chiral alanine-decorated PBI. The influence of the solvent’s dissolving capacity, the chirality of alanine, and the preparation methods on the morphologies and optical properties of the nanostructures were extensively studied. It was observed that the hierarchical nanostructures are formed by the reorganization of the 2D ribbon-like nanostructures. The size of the 2D ribbon-like nanostructures and the amount of the hierarchical nanostructures increase with the decrease in the solvent’s dissolving capacity. The small chiral alanine moiety is unable to induce chirality in the nanostructures, owing to its low steric hindrance and the dominant strong π-π stacking interaction of the PBI skeleton. A weaker π-π stacking interaction and better H-aggregated arrangement of the PBI skeleton could reduce the low-wavelength fluorescence intensity. The process of heating, cooling, and aging promotes the formation of H-aggregation in the PBI skeleton. The region of spectral overlap of the PBI solutions increases with the decrease in the dissolving capacity of the solvent and the steric hindrance of the chiral alanine. This study supplies a view to tailor the morphologies and optical properties of the nanostructures, which could be used as sensors and photocatalysts.

Purpose: Antibiotic-resistant bacterial pneumonia poses a significant therapeutic challenge. In China, Chinese herbal compound (CHC) is commonly used to treat bacterial pneumonia. We aimed to evaluate the efficacy and safety of CHC and identify core herb combinations for the treatment of multidrug-resistant or extensively drug-resistant bacterial pneumonia.Methods: Stata 16 and TSA 0.9.5.10 beta software were used for meta-analysis and trial sequential analysis (TSA), respectively. Exploring the sources of heterogeneity through meta-regression and subgroup analysis.Results: Thirty-eight studies involving 2890 patients were included in the analyses. Meta-analysis indicated that CHC combined with antibiotics improved the response rate (RR = 1.24; 95% CI: 1.19–1.28; p < 0.0001) and microbiological eradication (RR = 1.41; 95% CI: 1.27–1.57; p < 0.0001), lowered the white blood cell count (MD = −2.09; 95% CI: −2.65 to −1.53; p < 0.0001), procalcitonin levels (MD = −0.49; 95% CI: −0.59 to −0.40; p < 0.0001), C-reactive protein levels (MD = −11.80; 95% CI: −15.22 to −8.39; p < 0.0001), Clinical Pulmonary Infection Scores (CPIS) (MD = −1.97; 95% CI: −2.68 to −1.26; p < 0.0001), and Acute Physiology and Chronic Health Evaluation (APACHE)-II score (MD = −4.08; 95% CI: −5.16 to −3.00; p < 0.0001), shortened the length of hospitalization (MD = −4.79; 95% CI: −6.18 to −3.40; p < 0.0001), and reduced the number of adverse events. TSA indicated that the response rate and microbiological eradication results were robust. Moreover, Scutellaria baicalensis Georgi, Fritillaria thunbergii Miq, Lonicera japonica Thunb, and Glycyrrhiza uralensis Fisch were identified as core CHC prescription herbs.Conclusion: Compared with antibiotic treatment, CHC + antibiotic treatment was superior in improving response rate, microbiological eradication, inflammatory response, CPIS, and APACHE-II score and shortening the length of hospitalization. Association rule analysis identified four core herbs as promising candidates for treating antibiotic-resistant bacterial pneumonia. However, large-scale clinical studies are still required.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023410587.

Vacuum packaging is a superior procedure that could maintain the quality of dried red peppers for a relatively longer period, while the effect of light avoidance was inconsistent. Therefore, this study was to evaluate the effect of vacuum in combination with light avoidance on the storage quality of peppers and to investigate vacuum packaging and vacuum and light-avoided packaging influence the quality characteristics of dried chili peppers during storage. The results indicated that the quality characteristics of peppers gradually deteriorated: redness, extractable color, capsanthin, capsaicinoids, pungency, total phenolic content, and antioxidant capacity decreased, whereas moisture, water activity, and browning index increased as storage progressed. Vacuum packaging inhibited these changes compared with the control. Vacuum and light-avoided packaging further decelerated the quality loss of dried peppers, with the minimum changes in color, pungency, and antioxidant capacity of dried peppers during storage, and these could be due to lower water activity by light avoidance. Therefore, light avoidance may be necessary to further delay the deterioration of dried peppers under vacuum, and vacuum and light-avoided packaging could better retain the quality of dried chili peppers.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19.Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment.Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151).Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments.Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Fabricating hierarchical nanomaterials by self-assembly of rod-coil block copolymers attracts great interest. However, the key factors that affect the formation of the hierarchical nanomaterials have not been thoroughly researched. Herein, we have synthesized two diblock copolymers composed of poly(3-hexylthiophene) (P3HT) and polyethylene glycol (PEG). Through a heating, cooling, and aging process, a series of multilayered hierarchical micelles and fibers were prepared in alcoholic solutions. The transition from fibers to hierarchical micelles are strictly influenced by the strength of the π-π stacking interaction, the PEG chain length, and solvent. In isopropanol, the P3HT22-b-PEG43 could self-assemble into hierarchical micelles composed of several two-dimensional (2D) laminar layers, driven by the π-π stacking interaction and van der Waals force. The P3HT22-b-PEG43 could not self-assemble into well-defined nanostructures in methanol and ethanol, but could self-assemble into fibers in isobutanol. However, the P3HT22-b-PEG113 with a longer corona block only self-assembled into fibers in four alcoholic solutions, due to the increase in dissolving capacity and steric hindrance. The sizes and the size distributions of the nanostructures both increased with the increase in polymer concentration and the decrease in solvent polarity. This study shows a method to fabricate the hierarchical micelles.

Purpose: Antibiotic-resistant bacterial pneumonia poses a significant therapeutic challenge. In China, Chinese herbal compound (CHC) is commonly used to treat bacterial pneumonia. We aimed to evaluate the efficacy and safety of CHC and identify core herb combinations for the treatment of multidrug-resistant or extensively drug-resistant bacterial pneumonia. Methods: Stata 16 and TSA 0.9.5.10 beta software were used for meta-analysis and trial sequential analysis (TSA), respectively. Exploring the sources of heterogeneity through meta-regression and subgroup analysis. Results: Thirty-eight studies involving 2890 patients were included in the analyses. Meta-analysis indicated that CHC combined with antibiotics improved the response rate (RR = 1.24; 95% CI: 1.19-1.28; p < 0.0001) and microbiological eradication (RR = 1.41; 95% CI: 1.27-1.57; p < 0.0001), lowered the white blood cell count (MD = -2.09; 95% CI: -2.65 to -1.53; p < 0.0001), procalcitonin levels (MD = -0.49; 95% CI: -0.59 to -0.40; p < 0.0001), C-reactive protein levels (MD = -11.80; 95% CI: -15.22 to -8.39; p < 0.0001), Clinical Pulmonary Infection Scores (CPIS) (MD = -1.97; 95% CI: -2.68 to -1.26; p < 0.0001), and Acute Physiology and Chronic Health Evaluation (APACHE)-II score (MD = -4.08; 95% CI: -5.16 to -3.00; p < 0.0001), shortened the length of hospitalization (MD = -4.79; 95% CI: -6.18 to -3.40; p < 0.0001), and reduced the number of adverse events. TSA indicated that the response rate and microbiological eradication results were robust. Moreover, Scutellaria baicalensis Georgi, Fritillaria thunbergii Miq, Lonicera japonica Thunb, and Glycyrrhiza uralensis Fisch were identified as core CHC prescription herbs. Conclusion: Compared with antibiotic treatment, CHC + antibiotic treatment was superior in improving response rate, microbiological eradication, inflammatory response, CPIS, and APACHE-II score and shortening the length of hospitalization. Association rule analysis identified four core herbs as promising candidates for treating antibiotic-resistant bacterial pneumonia. However, large-scale clinical studies are still required. [ABSTRACT FROM AUTHOR]

Abstract Background Ferroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research. Methods Initially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes. Results According to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells. Conclusion We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

Abstract Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Abstract Background Lignin is an intricate phenolic polymer found in plant cell walls that has tremendous potential for being converted into value-added products with the possibility of significantly increasing the economics of bio-refineries. Although lignin in nature is bio-degradable, its biocatalytic conversion is challenging due to its stable complex structure and recalcitrance. In this context, an understanding of strain's genomics, enzymes, and degradation pathways can provide a solution for breaking down lignin to unlock the full potential of lignin as a dominant valuable bioresource. A gammaproteobacterial strain AORB19 has been isolated previously from decomposed wood based on its high laccase production. This work then focused on the detailed genomic and functional characterization of this strain based on whole genome sequencing, the identification of lignin degradation products, and the strain’s laccase production capabilities on various agro-industrial residues. Results Lignin degrading bacterial strain AORB19 was identified as Serratia quinivorans based on whole genome sequencing and core genome phylogeny. The strain comprised a total of 123 annotated CAZyme genes, including ten cellulases, four hemicellulases, five predicted carbohydrate esterase genes, and eight lignin-degrading enzyme genes. Strain AORB19 was also found to possess genes associated with metabolic pathways such as the β-ketoadipate, gentisate, anthranilate, homogentisic, and phenylacetate CoA pathways. LC–UV analysis demonstrated the presence of p-hydroxybenzaldehyde and vanillin in the culture media which constitutes potent biosignatures indicating the strain’s capability to degrade lignin. Finally, the study evaluated the laccase production of Serratia AORB19 grown with various industrial raw materials, with the highest activity detected on flax seed meal (257.71 U/L), followed by pea hull (230.11 U/L), canola meal (209.56 U/L), okara (187.67 U/L), and barley malt sprouts (169.27 U/L). Conclusions The whole genome analysis of Serratia quinivorans AORB19, elucidated a repertoire of genes, pathways and enzymes vital for lignin degradation that widens the understanding of ligninolytic metabolism among bacterial lignin degraders. The LC-UV analysis of the lignin degradation products coupled with the ability of S. quinivorans AORB19 to produce laccase on diverse agro-industrial residues underscores its versatility and its potential to contribute to the economic viability of bio-refineries.

According to the society of assisted reproductive technologies (SART), the top fertility clinics in North America have reported overall pregnancy rates of up to 50% in good prognosis patients. Although new techniques in advanced reproductive technologies have begun to emerge in the twenty-first century, including time-lapse monitoring of embryo development, analysis of metabolites in embryo culture media, and the use of artificial intelligence in morphometric embryo grading, currently chromosomal status obtained via pre-implantation genetic testing for aneuploidy (PGT-A) appears to be the most definitive in evaluating embryonic potential. Yet still, in most clinics, approximately 30% of euploid or chromosomally normal embryos fail to achieve a viable pregnancy resulting in stress and anxiety for patients, repeat cycles, and increased cost of treatment. Recent literature suggests that blastocysts with an increased mitochondrial DNA (mtDNA) ratio have greatly reduced implantation potential, however, there exists controversial studies which do not report a relationship. This review summarizes the current literature on utilizing mitochondrial DNA as a possible biomarker for embryo implantation, highlights the reasons for inconsistencies in some studies and suggests possible improvements to the study design of future mtDNA ratio research.

Abstract Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Hydrogen sulfide (H2S) is a crucial signaling molecule in plants. Recent studies have shown that H2S plays an equally important role as nitric oxide (NO) and hydrogen peroxide (H2O2) in plant signaling. Previous studies have demonstrated the involvement of H2S in regulating drought and other stressful environmental conditions, but the exact downstream molecular mechanisms activated by the H2S signaling molecule remain unclear. In this study, we conducted a comprehensive genome-wide transcriptomic analysis of both wild type (WT) and double mutant (lcd/des1). Arabidopsis thaliana plants were exposed to 40% polyethylene glycol (PEG) to induce drought stress and 20 µM sodium hydrosulfide (NaHS). The resulting transcriptome data were analyzed for differentially significant genes and their statistical enrichments in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated significant upregulation of genes related to photosynthesis, carbon fixation, plant secondary metabolite biosynthesis, inositol and phosphatidylinositol signaling pathways, and stress-responsive pathways in mutant plants under drought stress. Mutant plants with impaired H2S signaling mechanisms displayed greater susceptibility to drought stress compared to wild-type plants. In summary, all findings highlight the pivotal role of H2S signaling in stimulating other drought-responsive signaling pathways.

Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is rare and is associated with poor prognosis. However, the standard treatment protocols for patients with SCLC transformation remain unknown. Here, we report the case of a patient with advanced EGFR exon 19 deletion (19del) NSCLC who underwent SCLC transformation during targeted therapy. Biopsies and genetic testing were performed to adjust treatment regimens accordingly. The patient responded favorably to a combined treatment regimen comprising etoposide plus cisplatin chemotherapy and adebrelimab plus osimertinib. This case highlights the critical importance of acknowledging tumor heterogeneity in clinical decision-making and identifying potentially effective treatment options for patients with SCLC transformation. Additionally, we reviewed cases of the transformation of NSCLC to SCLC from 2017 to 2023.

BackgroundHIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear.MethodsThe expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients’ prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy.ResultsHIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p

Summary: Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (−2.24, 95% CI: −4.30 to −0.17; P = 0.0337), fatigue (−2.24, 95% CI: −4.46 to −0.02; P = 0.0479), constipation (−3.27, 95% CI −5.49 to −1.05; P = 0.0039), QLQ-OES18 pain (−1.77, 95% CI −3.11 to −0.43; P = 0.0097), trouble swallowing saliva (−2.09, 95% CI: −3.77 to −0.42; P = 0.0146), and choked when swallowing (−3.23, 95% CI: −5.60 to −0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61–0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35–0.67, P