Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Efficacy of a Virtual 3D Simulation-Based Digital Training Module for Building Dental Technology Students' Long-Term Competency in Removable Partial Denture Design: Prospective Cohort Study.

Background: Removable partial denture (RPD) design is crucial to long-term success in dental treatment, but shortcomings in RPD design training and competency acquisition among dental students have persisted for decades. Digital production is increasing in prevalence in stomatology, and a digital RPD (D-RPD) module, under the framework of the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT) system reported in our previous work, may improve on existing RPD training models for students. Objective: We aimed to determine the efficacy of a virtual 3D simulation-based progressive digital training module for RPD design compared to traditional training. Methods: We developed a prospective cohort study including dental technology students at the Stomatology College of Chongqing Medical University. Cohort 1 received traditional RPD design training (7 wk). Cohort 2 received D-RPD module training based on text and 2D sketches (7 wk). Cohort 3 received D-RPD module pilot training based on text and 2D sketches (4 wk) and continued to receive training based on 3D virtual casts of real patients (3 wk). RPD design tests based on virtual casts were conducted at 1 month and 1 year after training. We collected RPD design scores and the time spent to perform each assessment. Results: We collected the RPD design scores and the time spent to perform each assessment at 1 month and 1 year after training. The study recruited 109 students, including 58 (53.2%) female and 51 male (56.8%) students. Cohort 1 scored the lowest and cohort 3 scored the highest in both tests (cohorts 1-3 at 1 mo: mean score 65.8, SD 21.5; mean score 81.9, SD 6.88; and mean score 85.3, SD 8.55, respectively; P<.001; cohorts 1-3 at 1 y: mean score 60.3, SD 16.7; mean score 75.5, SD 3.90; and mean score 90.9, SD 4.3, respectively; P<.001). The difference between cohorts in the time spent was not statistically significant at 1 month (cohorts 1-3: mean 2407.8, SD 1370.3 s; mean 1835.0, SD 1329.2 s; and mean 1790.3, SD 1195.5 s, respectively; P=.06) but was statistically significant at 1 year (cohorts 1-3: mean 2049.16, SD 1099.0 s; mean 1857.33, SD 587.39 s; and mean 2524.3, SD 566.37 s, respectively; P<.001). Intracohort comparisons indicated that the differences in scores at 1 month and 1 year were not statistically significant for cohort 1 (95% CI -2.1 to 13.0; P=.16), while cohort 3 obtained significantly higher scores 1 year later (95% CI 2.5-8.7; P=.001), and cohort 2 obtained significantly lower scores 1 year later (95% CI -8.8 to -3.9; P<.001). Conclusions: Cohort 3 obtained the highest score at both time points with retention of competency at 1 year, indicating that progressive D-RPD training including virtual 3D simulation facilitated improved competency in RPD design. The adoption of D-RPD training may benefit learning outcomes.

Unravelling the veil of appearance anxiety: exploring social media use among Chinese young people.

The purpose of this study is to explore the relationship between appearance anxiety and social media use among Chinese adolescents. Using a grounded theory approach, the study conducted two-round online interviews with ten Chinese university students and subsequently constructed a theoretical model of social media appearance anxiety among Chinese young people. The results of the study indicate that social media has a dual impact on appearance anxiety. On one hand, increased social media engagement amplifies appearance anxiety by shaping aesthetic standards and fostering comparative environments. On the other hand, diverse aesthetic perspectives and authentic presentations on social media partially alleviate appearance anxiety by promoting acceptance of unique appearances and boosting self-confidence. It is emphasized in this study that there should be an in-depth understanding of the dual impact and complicated relationship of social media on the daily lives of Chinese adolescents to further develop relevant strategies that promote healthy social media behavior among youth. Furthermore, this study calls for efforts to actively promote the healthy image and psychological well-being of adolescents while alleviating the negative impact of appearance anxiety and overall mental health. Such efforts are needed to ensure a positive and healthy development for the younger generation.

Virtual and Interprofessional Objective Structured Clinical Examination in Dentistry and Dental Technology: Development and User Evaluations.

BACKGROUND: Interprofessional education (IPE) facilitates interprofessional collaborative practice (IPCP) to encourage teamwork among dental care professionals and is increasingly becoming a part of training programs for dental and dental technology students. However, the focus of previous IPE and IPCP studies has largely been on subjective student and instructor perceptions without including objective assessments of collaborative practice as an outcome measure. OBJECTIVE: The purposes of this study were to develop the framework for a novel virtual and interprofessional objective structured clinical examination (viOSCE) applicable to dental and dental technology students, to assess the effectiveness of the framework as a tool for measuring the outcomes of IPE, and to promote IPCP among dental and dental technology students. METHODS: The framework of the proposed novel viOSCE was developed using the modified Delphi method and then piloted. The lead researcher and a group of experts determined the content and scoring system. Subjective data were collected using the Readiness for Interprofessional Learning Scale and a self-made scale, and objective data were collected using examiner ratings. Data were analyzed using nonparametric tests. RESULTS: We successfully developed a viOSCE framework applicable to dental and dental technology students. Of 50 students, 32 (64%) participated in the pilot study and completed the questionnaires. On the basis of the Readiness for Interprofessional Learning Scale, the subjective evaluation indicated that teamwork skills were improved, and the only statistically significant difference in participant motivation between the 2 professional groups was in the mutual evaluation scale (P=.004). For the viOSCE evaluation scale, the difference between the professional groups in removable prosthodontics was statistically significant, and a trend for negative correlation between subjective and objective scores was noted, but it was not statistically significant. CONCLUSIONS: The results confirm that viOSCE can be used as an objective evaluation tool to assess the outcomes of IPE and IPCP. This study also revealed an interesting relationship between mutual evaluation and IPCP results, further demonstrating that the IPE and IPCP results urgently need to be supplemented with objective evaluation tools. Therefore, the implementation of viOSCE as part of a large and more complete objective structured clinical examination to test the ability of students to meet undergraduate graduation requirements will be the focus of our future studies.

Advances in Endoscopic Diagnosis and Treatment of Gastric Neuroendocrine Neoplasms.

Gastric neuroendocrine neoplasms refer to a group of diseases that are relatively rare. They can be classified into three subtypes based on their clinical and histopathological features, and there are significant differences in diagnosis, treatment, and prognosis among the different subtypes. The incidence of gastric neuroendocrine neoplasms has been increasing globally in recent years with the localized disease being particularly evident. Gastrointestinal endoscopy is of irreplaceable importance for the diagnosis and management of g-NENs. Endoscopy with biopsy is the gold standard for the diagnosis of g-NENs. Ultrasound endoscopy can assess the depth of tumor invasion and the presence of lymphatic metastases, which is important for the development of treatment strategies. Meanwhile, for some small and low-risk lesions, endoscopic surveillance or endoscopic resection has satisfactory therapeutic results and prognosis. This means that even though the incidence has increased, advances in endoscopic techniques have allowed more patients to adopt a relatively conservative treatment strategy. However, the criteria for patients suitable for endoscopic surveillance or endoscopic resection remain controversial.

State-of-the-Art Two-Dimensional Metal Phosphides for High Performance Lithium-ion Batteries: Progress and Prospects.

Lithium-ion batteries (LIBs) with high energy density, long cycle life and safety have earned recognition as outstanding energy storage devices, and have been used in extensive applications, such as portable electronics and new energy vehicles. However, traditional graphite anodes deliver low specific capacity and inferior rate performance, which is difficult to satisfy ever-increasing demands in LIBs. Very recently, two-dimensional metal phosphides (2D MPs) emerge as the cutting-edge materials in LIBs due to their overwhelming advantages including high theoretical capacity, excellent conductivity and short lithium diffusion pathway. This review summarizes the up-to-date advances of 2D MPs from typical structures, main synthesis methods and LIBs applications. The corresponding lithium storage mechanism, and relationship between 2D structure and lithium storage performance is deeply discussed to provide new enlightening insights in application of 2D materials for LIBs. Several potential challenges and inspiring outlooks are highlighted to provide guidance for future research and applications of 2D MPs.

Magnetic solid phase extraction coupled to HPLC-UV for highly sensitive analysis of mono-hydroxy polycyclic aromatic hydrocarbons in urine.

BACKGROUND: As a common pollutant, the carcinogenic properties of polycyclic aromatic hydrocarbons have garnered considerable attention. Trace metabolites of polycyclic aromatic hydrocarbons can be detected in urine as a non-invasively approach to monitor the exposure level. Nonetheless, the urine samples have the disadvantages of being large in volume and containing numerous impurities. Given the growing demand to study metabolites with low abundance and potential biomarkers, there is a pressing need for a preconcentration and high-throughput technique for effectively handling complex liquid samples. RESULTS: Polystyrene-coated magnetic nanoparticles were used to establish a novel magnetic extraction method for monohydroxy polycyclic aromatic hydrocarbons in urine samples. Polystyrene magnetic nanoparticles are an ideal absorbent for solid-phase extraction. After the material was mixed with the sample and adsorbed the target analyte, the analytes on the material were eluted and quantified using high-performance liquid chromatography. Influencing factors were optimized, and the proposed method achieved desirable sensitivity in analyzing low-abundance metabolites in large volumes of complex urine samples. The recoveries of intra-day and inter-day were 78.0-118.0 % and 81.0 %-115.0 %, respectively. The intra-day and inter-day reproducibility were less than 4.5 % and 8.6 %, respectively. The limits of detection were in the range of 0.009-0.041 ng mL-1, and the limits of quantification were in the range of 0.030-0.135 ng mL-1. SIGNIFICANCE AND NOVELTY: The application of reusable polystyrene-coated magnetic solid-phase nanoparticles as adsorbents makes the extraction of monohydroxy polycyclic aromatic hydrocarbons from urine samples economical and environmentally benign. The proposed method is simple, sensitive, and efficient compared to existing techniques. The nanoparticles are easy to prepare, showing potential for rapid screening of complex bulk bio-samples in batches with high efficiency and low budget.

Corrigendum: The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle.

Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined. Here, we investigate the structure of the DMV pore by in situ cryo-electron tomography combined with subtomogram averaging. We identify non-structural protein (nsp) 3 and 4 as minimal components required for the formation of a DMV-spanning pore, which is dependent on nsp3-4 proteolytic cleavage. In addition, we show that Mac2-Mac3-DPUP-Ubl2 domains are critical for nsp3 oligomerization and crown integrity which influences membrane curvature required for biogenesis of DMVs. Altogether, SARS-CoV-2 nsp3-4 have a dual role by driving the biogenesis of replication organelles and assembly of DMV-spanning pores which we propose here to term replicopores.

Oxidized sodium alginate/polyacrylamide hydrogels adhesive for promoting wheat growth.

Chemical modification of sodium alginate (SA) polymer chains can increase its functional group species. Sodium periodate (SP) was usually used to oxidize the hydroxyl groups on the chain of SA to aldehyde groups, the preparation of oxidized sodium alginate (OSA) using SP is not only complicated, also limits the variety of functional groups on the chain of OSA. By contrast, we have developed an innovative strategy for OSA, in which ammonium persulfate (APS) was used to oxidize SA, providing a clear elucidation of the oxidizing process and mechanism. OSA/PAM hydrogels were synthesized using OSA, the hydrogels possess excellent adhesion properties to various non-metallic and metallic substrates. Tensile and compression tests show that the cross-linked OSA/PAM hydrogels have superior mechanical properties. We exploit OSA/PAM hydrogels as soil adhesive and water-retaining agents for wheat growth. OSA/PAM hydrogels significantly improve the survival time of wheat grown in brown loam soil under a water-shortage environment, and slow down the wilting of wheat in a water-shortage environment and prolong the survival time of wheat in sandy soils. Our trials should make hydrogels important for wheat cultivation in brown loam soils and the development of desert areas.

N6-methyladenosine-regulated ADIRF impairs lung adenocarcinoma metastasis and serves as a potential prognostic biomarker.

Aberrant expression of adipogenic regulatory factors (ADIRF) in tumor cells is critical for tumor growth and metastasis. N6-methyladenosine (m6A) modifications have an important role in a variety of biological activities. Our study aimed to investigate the role of ADIRF in adenocarcinoma and to elucidate the regulatory role of m6A signaling on ADIRF. Differential expression of genes in tumor and normal tissues was analyzed using the LUAD dataset (GSE1987). The Kaplan-Meier method and receiver operating characteristic (ROC) curve analysis were performed to evaluate the prognostic and diagnostic value of ADIRF in LUAD. Loss-of-function or gain-of-function experiments were performed to study the effect of ADIRF on LUAD growth in vitro. The molecular mechanism of action of ADIRF in LUAD was confirmed using a dual-luciferase reporter system and MeRIP-qPCR. We identified a loss of ADIRF expression in LUAD tissues and cells. Furthermore, the restoration of ADIRF levels attenuated LUAD cell growth and metastasis in vitro. Mechanistically, an m6A "eraser," α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), eliminated the ADIRF m6A modification motif and further blocked the binding of the YTH domain-containing 2 (YTHDC2)-binding protein to ADIRF. At the molecular level, ALKBH5 enrichment increased ADIRF mRNA levels and prevented the attenuation of ADIRF mRNA by YTHDC2. The effects of ALKBH5 overexpression could also extend to the inhibition of LUAD cell proliferation and metastasis. This study linked ADIRF with the m6A modifying regulators ALKBH5 and YTHDC2, providing a promising molecular intervention for LUAD and deepening the understanding of LUAD mechanisms.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection.

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Recent Evidence on Polycyclic Aromatic Hydrocarbon Exposure.

This review provides a comprehensive conclusion of the relationship between the intake of various polycyclic aromatic hydrocarbons (PAHs) and different dietary patterns, pointing to the accompanying potential health risks. To achieve this, existing pertinent research was collected and analyzed. The collation revealed that the concentration of PAHs in food and their dietary patterns were diverse in different regions. Specifically, the concentration of PAHs in food was found to be related to the level of pollution in the area, including soil, air, and water pollution, which is then accumulated through the food chain into food that can be ingested directly by the human body, resulting in malformations in offspring, increased risk of cancer, and gene mutation. Guidebooks and dietary surveys were consulted to uncover disparities in dietary patterns, which indicated regional variations in taste preferences, traditional foods, and eating habits. Different regions are spatially categorized in this assessment by cities, countries, and continents. Notably, smoking and grilling are two of the food processing methods most likely to produce high levels of PAHs. To prevent excessive intake of PAHs from food items and attain a higher quality of life, more health education is urgently needed to promote healthy eating patterns.

Rapid and Sensitive Detection of Polycyclic Aromatic Hydrocarbons in Tea Leaves Using Magnetic Approach.

A rapid and efficient method using an alkyl-functionalized magnetic nanoparticles-based extraction technique combined with Ultra-High Performance Liquid Chromatography was developed for the detection of trace amounts of polycyclic aromatic hydrocarbons in tea leaves. As a popular coating for chromatographic column packing materials, C18-alkyl has been demonstrated to be effective in separating polycyclic aromatic hydrocarbons. Additionally, the magnetism of the nanomaterials accelerates the extraction process while their high surface ratio enables desirable dispersity in the sample matrix. Meanwhile, the adsorbents can be washed and reused 30 times without compromising recovery, which greatly reduces the budget. The effects of various parameters were investigated and optimized, and the recoveries for five analytes were in the range of 84.8-105.4%. The RSD of intra-day and inter-day were below 11.9% and 6.8%, respectively. The limits of detection and limits of quantification ranged from 1.69-9.97 ng g-1 and 5.12-30.21 ng g-1, indicating satisfactory sensitivity. Thus, the proposed methodology is rapid, highly efficient, and economical, and it expands the application of magnetic cleanup approaches in complex food matrices.

A pangenome reference of 36 Chinese populations.

Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference1. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.

Health prevention intervention for chronic tissue fibrosis: Based on the specific expression of CCL19/21 + mast cell.

Chronic tissue fibrosis is a common pathological feature of connective tissue diseases and malignant tumors, and its prevention has been a major focus of relevant research.However, the details of the mechanism of action of tissue-colonizing immune cells in fibroblast migration are unclear. In this study, connective tissue disease tissue specimens and solid tumor specimens were selected to observe the relationship between mast cells and interstitial fibrosis and the expression characteristics of mast cells. Our findings suggest that the number of mast cells in the tissue correlates with the degree of pathological fibrosis and that mast cells specifically express the chemokines CCL19 and CCL21, especially CCL19. CCR7+ fibroblasts are highly expressed in mast cell clusters. The mast cell line HMC-1 regulates CD14+ monocyte-derived fibroblasts via CCL19. In disease tissue fibrosis, mast cell activation may increase the expression of chemokines, especially CCL19, in the tissue, thereby inducing a large number of CCR7-positive fibroblasts to migrate to specific tissues. This study lays a foundation for the mechanism of tissue fibrosis and provides evidence for the mechanism by which mast cells induce fibroblast migration.Through the experimental results of this paper, we can combine the induction factors of chronic tissue fibrosis and put forward targeted health prevention strategies.

The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.